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DARZALEX® (daratumumab)

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DARZALEX - MMY3008 (MAIA) Study

Last Updated: 04/08/2025

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Click on the following links to related sections within the document: MAIA (MMY3008) Study Overview, Primary Analysis Results, Long-term Follow-up Analysis (64.5 Months), and Final Survival Analysis (89.3 months Month Follow-up).
Abbreviations: AE, adverse event; CI, confidence interval; CR, complete response; CrCl, creatinine clearance; Dara, daratumumab; D-Rd, daratumumab + lenalidomide + dexamethasone; ECOG PS, Eastern Cooperative Oncology Group performance status; HR, hazard ratio; IRR, infusion-related reaction; IV, intravenous; MRD, minimal residual disease; NA, not applicable; NDMM, newly diagnosed multiple myeloma; NR, not reached; ORR, overall response rate; OS, overall survival; PFS, progression-free survival; PFS2, PFS on the next line of therapy; Rd, lenalidomide + dexamethasone; sCR, stringent complete response; SPM, second primary malignancy; TEAE, treatment-emergent adverse event; VGPR, very good partial response.
aFacon (2019)1; bFacon (2018)2; cIn either treatment arm; dFacon (2025)3,4; eFacon (2024)5 ; fAll events were related to the general health condition of the patient.

SUMMARY  

  • MAIA is a phase 3 study evaluating the safety and efficacy of DARZALEX in combination with lenalidomide and dexamethasone (D-Rd) compared to lenalidomide and dexamethasone (Rd) in transplant-ineligible newly diagnosed multiple myeloma (NDMM) patients.1,2
    • Facon et al (2019)1 reported the pre-specified interim results of this ongoing study which indicated a 44% reduction in the risk of progression or death with D-Rd (hazard ratio [HR], 0.56; 95% confidence interval [CI], 0.43-0.73; P<0.001). Refer to Table: Most Common Adverse Events and Second Primary Cancers in the Safety Population for reported adverse event (AE) information.
    • Facon et al (2025)3 reported the updated efficacy and safety results from the MAIA study at a long-term median follow-up of 64.5 months. As of the clinical cutoff date of October 21, 2021, the median progression-free survival (PFS) was 61.9 months vs 34.4 months in the D-Rd vs Rd arm, respectively (HR, 0.55; 95% CI, 0.45-0.67; P<0.0001). The median overall survival (OS) was not reached (NR) in the D-Rd arm and was 65.5 months in the Rd arm (HR, 0.66; 95% CI, 0.53-0.83; P=0.0003). The D-Rd vs Rd arm showed a significantly higher (all P<0.0001) overall response rate (ORR; 92.9% vs 81.6%), complete response (CR) or better (≥CR) rate (51.1% vs 30.1%), and very good partial response (VGPR) or better (≥VGPR) rate (81.5% vs 56.9%). Similarly, the D-Rd vs Rd arm showed a significantly higher (all P<0.0001) minimal residual disease (MRD)-negativity (10-5 sensitivity) rate (32.1% [n=118] vs 11.1% [n=41]) and sustained MRD-negativity rate (10-5 sensitivity; ≥12 months: 18.8% [n=69] vs 4.1% [n=15]; ≥18 months: 16.8% [n=62] vs 3.3% [n=12]). No new safety concerns were observed with a longer follow-up. Grade 3/4 treatment-emergent adverse events (TEAEs) occurred in 95.9% vs 88.8% of patients from the D-Rd vs Rd arm, respectively. The most common (≥20%) grade 3/4 TEAEs with D-Rd vs Rd were neutropenia (54.1% vs 37.0%, respectively) and anemia (17.0% vs 21.6%, respectively). Grade 3/4 infections occurred in 42.6% vs 29.6% of patients from the D-Rd vs Rd arm, respectively. Serious TEAEs occurred in 78.8% vs 71.0% of patients from the D-Rd vs Rd arm, respectively, with pneumonia being the most common serious TEAE (18.7% vs 10.7%, respectively). The overall discontinuation rate due to TEAEs was lower in the D-Rd vs Rd arm (14.6% vs 23.8%). TEAEs leading to death were reported in 9.9% vs 9.3% of patients from the D-Rd vs Rd arm, respectively.
    • Facon et al (2024)5 presented the results of the updated efficacy and safety analysis of the MAIA study. At a median follow-up of 89.3 months (range, 0-102.2), a 33% reduction in the risk of death was observed with the D-Rd vs Rd arms. Median OS was reached for the D-Rd arm and was prolonged for patients in the D-Rd vs Rd arms (90.3 vs 64.1 months [HR, 0.67; 95% CI, 0.55-0.82; nominal P<0.0001]). The median time to subsequent antimyeloma therapy was 42.4 months in the Rd arm and NR in the D-Rd arm (HR, 0.51; 95% CI, 0.41-0.63; nominal P<0.0001). Deaths were reported for 47.5% (n=173) of patients in the D-Rd arm and 59.7% (n=218) of patients in the Rd arm, mostly due to disease progression.
  • Moreau et al (2025)6 reported the efficacy and safety results in clinically important subgroups of patients from the MAIA study. The PFS duration was longer in the D-Rd vs Rd arm in the majority of subgroups. Treatment with D-Rd generally resulted in a greater improvement in ORR, MRD-negativity (10-5) rate, and sustained MRD-negativity (10-5) rate for ≥12 months across subgroups, compared with Rd. Among patients aged ≥75 years, grade 3/4 TEAEs were reported in 95.5% vs 95.0% patients in the D-Rd vs Rd arm. The most common (≥10%) grade 3/4 TEAEs were neutropenia (D-Rd, 62.4%; Rd, 41.5%), lymphopenia (D-Rd, 21.0%; Rd, 12.6%), anemia (D-Rd, 20.4%; Rd, 25.2%), pneumonia (D-Rd, 20.4%; Rd, 14.5%), leukopenia (D-Rd, 12.1%; Rd, 7.5%), hypokalemia (D-Rd, 11.5%; Rd, 10.7%), hypertension (D-Rd, 10.8%; Rd, 5.0%), thrombocytopenia (D-Rd, 10.2%; Rd, 11.9%), and diarrhea (D-Rd, 10.2%; Rd, 5.0%).
  • Moreau et al (2022)7 presented the results of a post hoc analysis of the phase 3 MAIA study to evaluate the impact of treatment duration on long-term clinical outcomes. The median OS in the D-Rd arm was NR vs 20.5 months in patients who received treatment for ≥18 months vs <18 months, respectively. In patients who received treatment for ≥18 months, PFS benefit (HR, 0.57; 95% CI, 0.43-0.76; P<0.0001) and OS benefit (HR, 0.68; 95% CI, 0.47-0.98; P=0.0379) was observed in D-Rd vs Rd arms. Grade 3/4 TEAEs were reported in 96.5% vs 91.2% patients who received treatment for ≥18 months in the D-Rd vs Rd arm, respectively. The most common (≥15% in either treatment arm) grade 3/4 TEAEs were neutropenia (D-Rd, 56.9%; Rd, 41.2%), anemia (D-Rd, 17%; Rd, 18.1%), lymphopenia (D-Rd, 17%; Rd, 12.3%), pneumonia (D-Rd, 19.8%; Rd, 10.8%), and cataract (D-Rd, 13.8%; Rd, 18.6%).
  • Facon et al (2022)8 reported a post hoc subgroup analysis of frailty status in patients with NDMM ineligible for transplant in the MAIA study. Median PFS benefit was observed in the D-Rd vs Rd arm across all frailty subgroups. The most common serious TEAE was pneumonia and the most common reasons for treatment discontinuation across all frailty subgroups were progressive disease (PD) and AEs.
  • Jakubowiak et al (2022)9 conducted a pooled analysis of patient-level data from the MAIA and ALCYONE studies, analyzing PFS and best response in transplant-ineligible patients with NDMM and high-risk cytogenetic abnormalities (HRCAs).
  • Facon et al (2022)10 presented (at the 58th American Society of Clinical Oncology [ASCO] Annual Meeting) the results of a subgroup analysis of the phase 3 MAIA study that evaluated the efficacy and PROs of D-Rd vs Rd in subgroups of patients with NDMM who had renal impairment and/or high-risk cytogenetics.
  • San-Miguel et al (2022)11 presented an analysis of the predictive and prognostic role of MRD-negativity and durability in patients treated in the MAIA study. Patients receiving the D-Rd regimen achieved higher rates of MRD-negativity and durability compared with those receiving Rd.
  • Perrot et al (2025)12 published the final PRO analysis results from the MAIA study, with a median follow-up of 64.5 months.
  • Other relevant literature has been identified in addition to the data summarized above.13-20

PRODUCT LABELING

CLINICAL DATA

MAIA (MMY3008; NCT02252172) is an ongoing, international, phase 3, randomized, open-label, active-controlled, multicenter study in patients with NDMM not eligible for high-dose chemotherapy and autologous stem cell transplantation (ASCT; N=737).1,2 Facon et al (2019)1 reported the prespecified interim results of this ongoing study, which is summarized below. Bahlis et al (2019)21 presented updated safety and efficacy results from an additional 9-month follow-up in the MAIA study. Kumar et al (2020)22 presented updated safety and efficacy results after approximately 4 years of follow-up in the MAIA study. Facon et al (2021)23 reported the updated safety and efficacy results of the MAIA study at the pre-specified interim OS analysis with a median follow-up of 56.2 months. Facon et al (2025)3 reported the updated efficacy and safety results from the MAIA study at a long-term median follow-up of 64.5 months. Facon et al (2024)5 presented updated efficacy and safety results at a median follow-up of 89.3 months.

Study Design/Methods

  • Phase 3, multicenter, randomized, open-label, active-controlled (Rd arm), international study.
  • Key eligibility criteria: documented NDMM, ineligible for high-dose chemotherapy with ASCT due to age (≥65 years) or due to the presence of comorbidities impacting ASCT tolerability, Eastern Cooperative Oncology Group performance status (ECOG PS) 0-2, creatinine clearance (CrCl) ≥30 mL/min.
  • Patients were randomized 1:1 to D-Rd (n=368) or Rd (n=369) and received 28-day cycles of:
    • Patients in the Rd arm were administered until PD or unacceptable safety event:
      • Lenalidomide 25 mg orally (PO) daily on days 1-21 until PD (10 mg daily if CrCl between 30-50 mL/min).
      • Dexamethasone: 40 mg PO or IV weekly on days 1, 8, 15, and 22, until PD
        (20 mg weekly in patients >75 years of age or with a body mass index [BMI] <18.5 kg/m2).
    • Patients in the D-Rd arm were administered until PD or unacceptable safety event the same as above along with:
      • DARZALEX 16 mg/kg IV weekly during cycles 1-2, every 2 weeks during cycles 3-6, then every 4 weeks during cycle 7+. Following a protocol amendment (2020), patients in the D-Rd arm were given the option to switch from DARZALEX IV to DARZALEX FASPRO for subcutaneous (SC) use. DARZALEX FASPRO was to be administered at a fixed dose of 1800 mg SC over 3-5 minutes in the abdominal SC tissue once every 4 weeks.
  • Dose modifications:  
    • Delays in DARZALEX treatment were permissible if patients experienced any of the following AEs that could not be attributed to lenalidomide: grade 4 hematologic events, grade 3 thrombocytopenia with bleeding, febrile neutropenia, neutropenia with infection (any grade), and grade ≥3 nonhematologic AEs (excluding: grade 3 nausea, vomiting, diarrhea that responded to either antiemetics or antidiarrheal treatment within a week and grade 3 fatigue/asthenia that was existing at baseline or that lasted for <7 days after the last DARZALEX administration).23
  • Patients in the D-Rd arm were administered the following pre-infusion medications:23
    • Acetaminophen 650-1000 mg IV/PO
    • Diphenhydramine 25-50 mg (or equivalent) IV/PO
    • Dexamethasone 40 mg IV/PO approximately 1 hours prior to DARZALEX infusion
      (20 mg once weekly for patients >75 years of age or with a BMI <18.5 kg/m2)
  • For patients with a higher risk of respiratory complications such as mild asthma or chronic obstructive pulmonary disease who have forced expiratory volume in
    1 second <80% (FEV1); could receive the following post-infusion mediations: diphenhydramine (or equivalent), short-acting ß2 adrenergic receptor agonists, control medications for lung disease.23
  • Serum and urine samples were collected at screening, on day 1 of every cycle for
    2 years and every 8 weeks thereafter until PD.
  • Safety was monitored throughout the study until 30 days after the last dose of the study treatment.23
  • Cytogenetic risk was evaluated locally by fluorescence in situ hybridization (FISH) or karyotype testing. High-risk cytogenetics was determined by a deletion (del)17p and/or translocations t(14;16), or t(4;14).
  • Primary endpoint: PFS.
  • Secondary endpoints: ≥CR rate, duration of response, ≥VGPR rate; MRD-negativity rate, ORR, OS, time from randomization to disease progression on the next line of therapy or death (PFS2), safety, stringent complete response (sCR), time to next (2nd-line) treatment, time to response, and time to progression.

Primary Analysis of the MAIA Study

Results

Efficacy
  • Median follow-up: 28.0 months (range, 0.0-41.4)
  • Patients (52% male) ranged in age from 45-90 years (median, 73 years; 70-<75 years, 35%; ≥75 years, 44%), with key baseline characteristics being well-balanced between the arms.
  • HR for the primary endpoint of PFS: 0.56 (95% CI, 0.43-0.73; P<0.001) indicating a 44% reduction in the risk of progression or death with D-Rd.
  • Median time to first response was 1.05 months in both arms.
  • Median PFS: 31.9 months for Rd (95% CI, 28.9-NR); NR for D-Rd
    • PFS was maintained among patients ≥75 years (HR, 0.63; 95% CI, 0.44-0.92).
  • ORR: 92.9% (95% CI, 89.8-95.3) for D-Rd vs 81.3% (95% CI, 76.9-85.1) for Rd (P<0.001)
  • ≥CR was achieved in 175 (47.6%) patients in the D-Rd arm vs 92 (24.9%) patients in the Rd arm (P<0.001).
  • Median time to ≥CR was 10.4 months for D-Rd and 11.2 months for Rd.
  • ≥VGPR of 79.3% was reported for D-Rd vs 53.1% for Rd (P<0.001).
  • MRD-negativity was >3 times higher with D-Rd than with Rd (89 [24.2%] vs 27 [7.3%]; P<0.001).
  • HR for OS: 0.78 (95% CI, 0.56-1.1); data immature after a median follow-up of 28.0 months
Safety
  • Serious AEs: 62.9% for D-Rd; 62.7% for Rd
  • AEs leading to discontinuation: 7.1% for D-Rd; 15.9% for Rd
  • TEAEs with outcome of death: 6.9% for D-Rd; 6.3% for Rd
    • Pneumonia was the most common AE that resulted in death (D-Rd, 0.5%; Rd, 0.8%).

Most Common Adverse Events and Second Primary Cancers in the Safety Populationa, 1
Event, n (%)
D-Rd (n=364)
Rd (n=365)
Any Grade
Grade 3/4
Any Grade
Grade 3/4
Hematologic
   Neutropenia
207 (56.9)
182 (50.0)
154 (42.2)
129 (35.3)
   Anemia
126 (34.6)
43 (11.8)
138 (37.8)
72 (19.7)
   Leukopenia
68 (18.7)
40 (11.0)
34 (9.3)
18 (4.9)
   Lymphopenia
66 (18.1)
55 (15.1)
45 (12.3)
39 (10.7)
Nonhematologic
   Infections
314 (86.3)
117 (32.1)
268 (73.4)
85 (23.3)
      Pneumonia
82 (22.5)
50 (13.7)
46 (12.6)
29 (7.9)
   Diarrhea
207 (56.9)
24 (6.6)
168 (46.0)
15 (4.1)
   Constipation
149 (40.9)
6 (1.6)
130 (35.6)
1 (0.3)
   Fatigue
147 (40.4)
29 (8.0)
104 (28.5)
14 (3.8)
   Peripheral edema
140 (38.5)
7 (1.9)
107 (29.3)
2 (0.5)
   Back Pain
123 (33.8)
11 (3.0)
96 (26.3)
11 (3.0)
   Asthenia
117 (32.1)
16 (4.4)
90 (24.7)
13 (3.6)
   Nausea
115 (31.6)
5 (1.4)
84 (23.0)
2 (0.5)
Second primary cancerb
32 (8.8)
NA
26 (7.1)
NA
   Invasive second primary cancer
12 (3.3)
NA
13 (3.6)
NA
Any infusion-related reaction
149 (40.9)
10 (2.7)
NA
NA
Abbreviations: D-Rd, DARZALEX + lenalidomide + dexamethasone; NA, not applicable; Rd, lenalidomide + dexamethasone.
aThe safety population included all patients who received at least one dose of the trial treatment. Adverse events of any grade that were reported in >30% of patients in either treatment arm and grade 3/4 adverse events that were reported in >10% of patients in either treatment arm are listed.
bThe presence of a second primary cancer was prespecified in the statistical analysis plan as an adverse event of clinical interest.

Long-term Efficacy and Safety Analysis of the MAIA Study

Facon et al (2025)3 reported the updated efficacy and safety results from the MAIA study at a long-term median follow-up of 64.5 months.

Results

Patient Characteristics

Demographic and Baseline Disease Characteristics of the ITT Population4
Characteristic
D-Rd
(n=368)
Rd
(n=369)
Age
   Median (range), years
73.0 (50-90)
74.0 (45-89)
ECOG PSa, n (%)
   0
127 (34.5)
123 (33.3)
   1
178 (48.4)
187 (50.7)
   ≥2
63 (17.1)
59 (16.0)
ISS disease stageb, n (%)
   I
98 (26.6)
103 (27.9)
   II
163 (44.3)
156 (42.3)
   III
107 (29.1)
110 (29.8)
Type of measurable disease, n (%)
   IgG
225 (61.1)
231 (62.6)
   IgA
65 (17.7)
66 (17.9)
   Otherc
9 (2.4)
10 (2.7)
   Detected in urine only
40 (10.9)
34 (9.2)
   Detected in serum FLC only
29 (7.9)
28 (7.6)
Cytogenetic riskd
   n
319
323
   Standard risk, n (%)
271 (85.0)
279 (86.4)
   High risk, n (%)
48 (15.0)
44 (13.6)
Median (range) time since initial diagnosis of MM, months
0.95 (0.1-13.3)
0.89 (0-14.5)
Abbreviations: del, deletion; D-Rd, DARZALEX + lenalidomide + dexamethasone; ECOG PS, Eastern Cooperative Oncology Group performance status; FLC, free light chain; Ig, immunoglobulin; ISS, International Staging System; ITT, intent-to-treat; MM, multiple myeloma; Rd, lenalidomide + dexamethasone; t, translocation.
aECOG PS is scored on a scale of 0 to 5, with 0 indicating no symptoms and higher scores indicating increasing disability.
bISS disease stage was based on the combination of serum β2-microglobulin and albumin.
cIncludes IgD, IgE, IgM, and biclonal disease.
dCytogenetic risk was assessed by fluorescence in situ hybridization or karyotype testing; high risk was defined as the presence of t(4;14), t(14;16), or del(17p).

Demographic and Baseline Disease Characteristics Based on Age Subgroups4
Characteristic
<70 Years
≥70 to <75 Years
≥75 Years
≥80 Years
D-Rd
(n=78)
Rd
(n=77)
D-Rd
(n=130)
Rd
(n=131)
D-Rd
(n=160)
Rd
(n=161)
D-Rd
(n=66)
Rd
(n=71)
Age
   Median (range), years
68
(50-69)
68
(45-69)
72
(70-74)
72
(70-74)
78
(75-90)
79
(75-89)
82
(79-90)
82
(80-89)
ECOG PSa, n (%)
   0
34 (43.6)
28 (36.4)
42 (32.3)
48 (36.6)
51 (31.9)
47 (29.2)
21 (31.8)
18 (25.4)
   1
31 (39.7)
37 (48.1)
69 (53.1)
67 (51.1)
78 (48.8)
83 (51.6)
32 (48.5)
37 (52.1)
   ≥2
13 (16.7)
12 (15.6)
19 (14.6)
16 (12.2)
31 (19.4)
31 (19.3)
13 (19.7)
16 (22.5)
ISS disease stageb, n (%)
   I
31 (39.7)
25 (32.5)
34 (26.2)
41 (31.3)
33 (20.6)
37 (23.0)
13 (19.7)
13 (18.3)
   II
21 (26.9)
32 (41.6)
67 (51.5)
54 (41.2)
75 (46.9)
70 (43.5)
27 (40.9)
28 (39.4)
   III
26 (33.3)
20 (26.0)
29 (22.3)
36 (27.5)
52 (32.5)
54 (33.5)
26 (39.4)
30 (42.3)
Type of measurable disease, n (%)
   IgG
44 (56.4)
45 (58.4)
79 (60.8)
82 (62.6)
102 (63.8)
104 (64.6)
41 (62.1)
41 (57.7)
   IgA
13 (16.7)
18 (23.4)
26 (20.0)
21 (16.0)
26 (16.3)
27 (16.8)
13 (19.7)
10 (14.1)
   Otherc
2 (2.6)
1 (1.3)
2 (1.5)
4 (3.1)
5 (3.1)
5 (3.1)
2 (3.0)
4 (5.6)
   Detected in urine only
12 (15.4)
9 (11.7)
12 (9.2)
12 (9.2)
16 (10.0)
13 (8.1)
4 (6.1)
8 (11.3)
   Detected in serum FLC only
7 (9.0)
4 (5.2)
11 (8.5)
12 (9.2)
11 (6.9)
12 (7.5)
6 (9.1)
8 (11.3)
Cytogenetic riskd, n (%)
   n
66
66
112
119
141
138
57
60
   Standard risk
56 (84.8)
58 (87.9)
98 (87.5)
103 (86.6)
117 (83.0)
118 (85.5)
47 (82.5)
52 (86.7)
   High risk
10 (15.2)
8 (12.1)
14 (12.5)
16 (13.4)
24 (17.0)
20 (14.5)
10 (17.5)
8 (13.3)
Median (range) time since initial diagnosis of MM, months
0.85 (0.2-6.2)
0.82 (0.3-14.5)
0.90 (0.1-8.7)
0.95 (0.2-9.2)
0.95 (0.2-13.3)
0.92 (0.0-9.2)
1.02 (0.2-13.3)
0.95 (0.0-9.2)
Abbreviations: del, deletion; D-Rd, DARZALEX + lenalidomide + dexamethasone; ECOG PS, Eastern Cooperative Oncology Group performance status; FLC, free light chain; Ig, immunoglobulin; ISS, International Staging System; MM, multiple myeloma; Rd, lenalidomide/dexamethasone; t, translocation.
aECOG PS is scored on a scale of 0 to 5, with 0 indicating no symptoms and higher scores indicating increasing disability.
bISS disease stage was based on the combination of serum β2-microglobulin and albumin.
cIncludes IgD, IgE, IgM, and biclonal disease.
dCytogenetic risk was assessed by fluorescence in situ hybridization or karyotype testing; high risk was defined as the presence of t(4;14), t(14;16), or del(17p).

Treatment Exposure in the Overall Safety Population4
Parameter
D-Rd
(n=364)
Rd
(n=365)
Median (range) number of treatment cycles
51 (1-83)
24 (1-82)
Relative dose intensity
DARZALEX
      n
364
0
      Median (range), %
98.0 (3.2-107.0)
-
Lenalidomide
      n
326
338
      Median (range), %
65.0 (7.9-202.1)
83.4 (4.8-239.3)
Dexamethasone
      n
364
365
      Median (range), %
76.5 (21.9-110.7)
84.8 (18.9-154.5)
Abbreviations: D-Rd, DARZALEX + lenalidomide + dexamethasone; Rd, lenalidomide/dexamethasone.

Patient Disposition and Treatment Discontinuation According to Age Group (MAIA - Long-term Follow-up)3,4
Parameter
<70 Years
≥70 to <75 Years
≥75 Years
≥80 Years
D-Rd (n=78)
Rd (n=77)
D-Rd (n=130)
Rd (n=131)
D-Rd (n=160)
Rd (n=161)
D-Rd (n=66)
Rd (n=71)
Patients treateda,
n (%)
78
(100)
76
(98.7)
129
(99.2)
130
(99.2)
157
(98.1)
159
(98.8)
65
(98.5)
70
(98.6)
Patients who discontinued treatmentb, n (%)
37
(47.4)
64
(84.2)
79
(61.2)
106
(81.5)
117
(74.5)
141
(88.7)
44
(67.7)
64
(91.4)
   Reasons for discontinuation, n (%)
      PD
17 (21.8)
34 (44.7)
42 (32.6)
47 (36.2)
48 (30.6)
50 (31.4)
20 (30.8)
22 (31.4)
      AE
9 (11.5)
12 (15.8)
20 (15.5)
33 (25.4)
28 (17.8)
44 (27.7)
6 (9.2)
21 (30.0)
      Noncompliance with study drug
5 (6.4)
5 (6.6)
7 (5.4)
7 (5.4)
9 (5.7)
18 (11.3)
5 (7.7)
7 (10.0)
      Death
5 (6.4)
2 (2.6)
5 (3.9)
7 (5.4)
14 (8.9)
16 (10.1)
6 (9.2)
6 (8.6)
      Physician’s decision
1 (1.3)
9 (11.8)
3 (2.3)
7 (5.4)
12 (7.6)
8 (5.0)
3 (4.6)
6 (8.6)
      Patient withdrawal
0 (0)
2 (2.6)
1 (0.8)
3 (2.3)
1 (0.6)
3 (1.9)
0 (0)
0 (0)
      Lost to follow-up
0 (0)
0 (0)
0 (0)
0 (0)
1 (0.6)
2 (1.3)
1 (1.5)
2 (2.9)
      Other
0 (0)
0 (0)
1 (0.8)
2 (1.5)
4 (2.5)
0 (0)
3 (4.6)
0 (0)
Abbreviations: AE, adverse event; D-Rd, DARZALEX + lenalidomide + dexamethasone; PD, progressive disease; Rd, lenalidomide + dexamethasone.
aPercentages are based on the number of patients randomized.
bPercentages are based on the number of patients treated.
Efficacy
  • The median PFS was 61.9 months vs 34.4 months in the D-Rd vs Rd arm, respectively (HR, 0.55; 95% CI, 0.45-0.67; P<0.0001).3
  • The most common reasons for confirmed PD in each group were biochemical (D-Rd, 76.2%; Rd, 83.6%), bone lesions (D-Rd, 16.4%; Rd, 13.6%), plasmacytomas (D-Rd, 8.2%; Rd, 4.5%), and other causes (D-Rd, 1.6%; Rd, 2.3%).3
  • The median OS was NR in the D-Rd arm and was 65.5 months in the Rd arm (HR, 0.66; 95% CI, 0.53-0.83; P=0.0003).3
  • The D-Rd vs Rd arm showed a significantly higher (all P<0.0001) ORR (92.9% vs 81.6%), ≥CR rate (51.1% vs 30.1%), and ≥VGPR rate (81.5% vs 56.9%) as presented in Table: Response Rates in the ITT Population.
    • The ORR, ≥CR rate, and ≥VGPR rate were higher for the D-Rd vs Rd arm across all age subgroups and are summarized in Table: Response Rates Based on Age Subgroups.
    • The cumulative best response rate improved with continuous D-Rd treatment in patients who achieved ≥CR and ≥VGPR.
    • Continued D-Rd treatment markedly deepened the best response rate over time, with the ≥CR rate increasing from 8.2% by 6 months to 28.0% by 12 months, 40.8% by 18 months, 45.4% by 24 months, 48.1% by 30 months, and 51.1% by 48 months.
    • For patients who achieved ≥CR
      • The median PFS was NR in either treatment arm (HR, 0.52; 95% CI, 0.35-0.76; P=0.0007).
      • The estimated 60-month PFS rate was 73.7% vs 53.8% in the D-Rd vs Rd arm, respectively.
      • The median OS was NR in either treatment arm (HR, 0.58; 95% CI, 0.37-0.91; P=0.0164).
      • The estimated 60-month OS rate was 81.7% vs 69.1% in the D-Rd vs Rd arm, respectively.
    • For patients who achieved VGPR
      • The median PFS was 42.7 months vs 36.2 months in the D-Rd vs Rd, respectively (HR, 0.71; 95% CI, 0.51-0.99; P=0.0401).
      • The estimated 60-month PFS rate was 37.1% vs 23.2% in the D-Rd vs Rd arm, respectively.
      • The median OS was NR in the D-Rd arm and was 63.1 months in the Rd arm (HR, 0.78; 95% CI, 0.53-1.16; P=0.2256).
      • The estimated 60-month OS rate was 61.5% vs 53.0% in the D-Rd vs Rd arm, respectively.
  • The D-Rd vs Rd arm showed a significantly higher (all P<0.0001) MRD-negativity rate (10-5 sensitivity; 32.1% vs 11.1%) and sustained MRD-negativity rate (10-5 sensitivity; ≥12 months, 18.8% vs 4.1%; ≥18 months, 16.8% vs 3.3%) as summarized in Table: Response Rates in the ITT Population.3
    • The MRD-negativity response rate deepened over time, increasing from 12.8% at 12 months to 20.4% at 18 months, 24.2% at 24 months, 27.4% at 30 months, 29.3% at 36 months, 31.5% at 48 months, and 31.8% at 60 months.
    • The D-Rd vs Rd arm was associated with an increased MRD-negativity rate across all age subgroups as summarized in Table: Response Rates Based on Age Subgroups.
    • PFS and OS improved in patients who achieved MRD-negativity vs those who were MRD-positive in both treatment arms, with more patients in the D-Rd arm achieving MRD-negativity.
  • A total of 128 (35.2%) vs 194 (53.2%) patients from the D-Rd vs Rd arm, respectively, received subsequent therapy.3
    • In the D-Rd vs Rd arm, 9.4% vs 23.2% of patients received DARZALEX-containing treatment as their first subsequent therapy, respectively.
    • In the D-Rd vs Rd arm, 14.1% vs 48.5% of patients received DARZALEX-containing treatment as any subsequent line of therapy, respectively.
    • PFS on next line of therapy was 73.7 months vs 48.9 months in the D-Rd vs Rd arm, respectively (HR, 0.61; 95% CI, 0.49-0.76; P<0.0001).

Analysis of PFS in Pre-specified Patient Subgroupsa,4
Subgroup
D-Rd
Rd
HR (95% CI)b
n/N
Median PFS, Months
n/N
Median PFS, Months
Sex
   Male
91/189
61.9
120/195
32.3
0.57 (0.44-0.76)
   Female
85/179
62.1
108/174
35.4
0.54 (0.40-0.71)
Age
   <75 years
89/208
NE
122/208
37.5
0.52 (0.39-0.68)
   ≥75 years
87/160
54.3
106/161
31.4
0.59 (0.44-0.79)
Race
   White
161/336
61.9
208/339
34.5
0.55 (0.45-0.67)
   Other
15/32
62.1
20/30
30.4
0.59 (0.30-1.16)
Region
   North America
49/101
58.2
60/102
30.4
0.57 (0.39-0.83)
   Other
127/267
61.9
168/267
36.9
0.55 (0.43-0.69)
Baseline renal function (CrCl)
   >60 mL/min
94/206
73.7
136/227
37.4
0.54 (0.41-0.70)
   ≤60 mL/min
82/162
56.7
92/142
29.7
0.55 (0.41-0.75)
Baseline hepatic function
   Normal
157/335
62.8
211/340
33.8
0.52 (0.43-0.65)
   Impaired
19/31
29.2
17/29
35.1
0.99 (0.51-1.91)
ISS disease stage
   I
38/98
NE
48/103
52.5
0.65 (0.42-1.00)
   II
77/163
63.8
107/156
29.7
0.46 (0.34-0.62)
   III
61/107
42.4
73/110
24.2
0.61 (0.43-0.86)
Type of MM
   IgG
112/225
60.7
135/231
38.7
0.69 (0.53-0.88)
   Non-IgG
34/74
63.8
53/76
23.5
0.39 (0.25-0.60)
Cytogenetic risk at study entry
   High riskc
28/48
45.3
31/44
29.6
0.57 (0.34-0.96)
   Standard risk
126/271
63.8
174/279
34.4
0.51 (0.41-0.64)
ECOG PS
   0
54/127
NE
74/123
39.6
0.51 (0.36-0.72)
   1
90/178
58.2
113/187
35.1
0.58 (0.44-0.77)
   ≥2
32/63
48.4
41/59
23.5
0.56 (0.35-0.89)
Abbreviations: CI, confidence interval; CrCl, creatinine clearance; del, deletion; D-Rd, DARZALEX + lenalidomide + dexamethasone; ECOG PS, Eastern Cooperative Oncology Group performance status; HR, hazard ratio; IgG, immunoglobulin G; ISS, International Staging System; ITT, intent-to-treat; MM, multiple myeloma; NE, not estimable; PFS, progression-free survival; Rd, lenalidomide + dexamethasone; t, translocation.
aAnalysis of PFS in subgroups of the ITT population, which were defined according to baseline characteristics.
bHRs and 95% CIs from a Cox proportional hazards model with treatment as the sole explanatory variable. HR <1 indicates an advantage for D-Rd.
cPatients at a high cytogenetic risk tested positive for ≥1 of the following cytogenetic abnormalities on fluorescence in situ hybridization or karyotype testing: del(17p), t(14;16), or t(4;14).

Analysis of OS in Pre-specified Patient Subgroupsa,4
Subgroup
D-Rd
Rd
HR (95% CI)b
n/N
Median OS, Months
n/N
Median OS, Months
Sex
   Male
76/189
NE
101/195
61.0
0.71 (0.53-0.96)
   Female
56/179
73.7
75/174
68.6
0.63 (0.45-0.89)
Age
   <75 years
59/208
NE
90/208
NE
0.59 (0.43-0.83)
   ≥75 years
73/160
73.7
86/161
54.8
0.75 (0.55-1.02)
Race
   White
120/336
NE
158/339
66.4
0.69 (0.54-0.87)
   Other
12/32
NE
18/30
49.1
0.52 (0.25-1.07)
Region
   North America
36/101
NE
52/102
54.8
0.60 (0.39-0.92)
   Other
96/267
NE
124/267
66.9
0.70 (0.54-0.91)
Baseline renal function (CrCl)
   >60 mL/min
70/206
NE
102/227
68.6
0.67 (0.49-0.90)
   ≤60 mL/min
62/162
NE
74/142
54.8
0.65 (0.46-0.90)
Baseline hepatic function
   Normal
117/335
NE
164/340
65.4
0.63 (0.50-0.80)
   Impaired
15/31
66.1
12/29
NE
1.23 (0.57-2.63)
ISS disease stage
   I
21/98
NE
29/103
NE
0.71 (0.40-1.24)
   II
60/163
73.7
79/156
61.7
0.62 (0.44-0.87)
   III
51/107
66.1
68/110
47.3
0.69 (0.48-1.00)
Type of MM
   IgG
83/225
NE
102/231
68.6
0.78 (0.58-1.04)
   Non-IgG
26/74
NE
40/76
53.7
0.54 (0.33-0.88)
Cytogenetic risk at study entry
   High riskc
27/48
55.6
28/44
42.5
0.81 (0.48-1.38)
   Standard risk
90/271
NE
131/279
65.5
0.62 (0.48-0.81)
ECOG PS
   0
28/127
NE
41/123
NE
0.62 (0.38-1.01)
   1
73/178
73.7
96/187
58.3
0.70 (0.51-0.95)
   ≥2
31/63
61.9
39/59
39.0
0.61 (0.38-0.97)
Abbreviations: CI, confidence interval; CrCl, creatinine clearance; del, deletion; D-Rd, DARZALEX + lenalidomide + dexamethasone; ECOG PS, Eastern Cooperative Oncology Group performance status; HR, hazard ratio; IgG, immunoglobulin G; ISS, International Staging System; ITT, intent-to-treat; MM, multiple myeloma; NE, not estimable; OS, overall survival; Rd, lenalidomide + dexamethasone; t, translocation.
aAnalysis of OS in subgroups of the ITT population, which were defined according to baseline characteristics.
bHRs and 95% CIs from a Cox proportional hazards model with treatment as the sole explanatory variable. HR <1 indicates an advantage for D-Rd.
cPatients at a high cytogenetic risk tested positive for ≥1 of the following cytogenetic abnormalities on fluorescence in situ hybridization or karyotype testing: del(17p), t(14;16), or t(4;14).

Response Rates in the ITT Population3
Response, n (%)
D-Rd
(n=368)
Rd
(n=369)
P Value
ORR
342 (92.9)
301 (81.6)
<0.0001a
   ≥CR
188 (51.1)
111 (30.1)
<0.0001a
      sCR
131 (35.6)
58 (15.7)
<0.0001a
      CR
57 (15.5)
53 (14.4)
-
  ≥VGPR
300 (81.5)
210 (56.9)
<0.0001a
      VGPR
112 (30.4)
99 (26.8)
-
   PR
42 (11.4)
91 (24.7)
-
SD
11 (3.0)
55 (14.9)
-
PD
1 (0.3)
0 (0)
-
NE
14 (3.8)
13 (3.5)
-
MRD-negativity response rate (10-5 sensitivity), n (%)
118 (32.1)
41 (11.1)
<0.0001b
Sustained MRD-negativity response rate (10-5 sensitivity), n (%)
≥12 months
69 (18.8)
15 (4.1)
<0.0001b
≥18 months
62 (16.8)
12 (3.3)
<0.0001b
Abbreviations: CR, complete response; D-Rd, DARZALEX + lenalidomide + dexamethasone; ITT, intent-to-treat; NE, not estimable; ORR, overall response rate; PD, progressive disease; PR, partial response; Rd, lenalidomide + dexamethasone; sCR, stringent complete response; SD, stable disease; VGPR, very good partial response.
aP value was calculated using the Cochran-Mantel-Haenszel chi-square test.
bP value was calculated using the Fisher’s exact test.

Response Rates Based on Age Subgroups3
Response, n (%)
Age <70 Years
Age ≥70 to <75 Years
Age ≥75 Years
Age ≥80 Years
D-Rd
(n=78)
Rd
(n=77)
P Value
D-Rd
(n=130)
Rd
(n=131)
P Value
D-Rd
(n=160)
Rd
(n=161)
P Value
D-Rd
(n=66)
Rd
(n=71)
P Value
ORR
73 (93.6)
62 (80.5)
0.0156a
125 (96.2)
108 (82.4)
0.0004a
144 (90.0)
131 (81.4)
0.0275a
59 (89.4)
55 (77.5)
0.0629a
   ≥CR
44 (56.4)
24 (31.2)
0.0016a
73 (56.2)
41 (31.3)
<0.0001a
71 (44.4)
46 (28.6)
0.0033a
29 (43.9)
15 (21.1)
0.0044a
      sCR
31 (39.7)
11 (14.3)
0.0004a
50 (38.5)
23 (17.6)
0.0002a
50 (31.3)
24 (14.9)
0.0005
23 (34.8)
8 (11.3)
0.0010a
      CR
13 (16.7)
13 (16.9)
-
23 (17.7)
18 (13.7)
-
21 (13.1)
22 (13.7)
-
6 (9.1)
7 (9.9)
-
   ≥VGPR
64 (82.1)
45 (58.4)
0.0013a
111 (85.4)
76 (58.0)
<0.0001a
125 (78.1)
89 (55.3)
<0.0001a
50 (75.8)
31 (43.7)
0.0001a
      VGPR
20 (25.6)
21 (27.3)
-
38 (29.2)
35 (26.7)
-
54 (33.8)
43 (26.7)
-
21 (31.8)
16 (22.5)
-
   PR
9 (11.5)
17 (22.1)
-
14 (10.8)
32 (24.4)
-
19 (11.9)
42 (26.1)
-
9 (13.6)
24 (33.8)
-
SD
1 (1.3)
14 (18.2)
-
3 (2.3)
20 (15.3)
-
7 (4.4)
21 (13.0)
-
3 (4.5)
11 (15.5)
-
PD
0 (0)
0 (0)
-
0 (0)
0 (0)
-
1 (0.6)
0 (0)
-
0 (0)
0 (0)
-
NE
4 (5.1)
1 (1.3)
-
2 (1.5)
3 (2.3)
-
8 (5.0)
9 (5.6)
-
4 (6.1)
5 (7.0)
-
MRD-negativity response rate, n (%)
28 (35.9)
9 (11.7)
0.0006
47 (36.2)
16 (12.2)
0.0001
43 (26.9)
16 (9.9)
0.0001
17 (25.8)
4 (5.6)
0.0016
Abbreviations: CR, complete response; D-Rd, DARZALEX + lenalidomide + dexamethasone; MRD, minimal residual disease; NE, not estimable; ORR, overall response rate; PD, progressive disease; PR, partial response; Rd, lenalidomide + dexamethasone; sCR, stringent complete response; SD, stable disease; VGPR, very good partial response.
aP value was calculated using the Cochran-Mantel-Haenszel chi-square test.

PFS and OS Based on Age Subgroups3
Parameter
Age <70 Years
Age ≥70 to <75 Years
Age ≥75 Years
Age ≥80 Years
D-Rd
(n=78)
Rd
(n=77)
HR (95% CI)
P Value
D-Rd
(n=130)
Rd
(n=131)
HR (95% CI)
P Value
D-Rd
(n=160)
Rd
(n=161)
HR (95% CI)
P Value
D-Rd
(n=66)
Rd
(n=71)
HR (95% CI)
P Value
PFS
Median,  months
NR
39.2
0.35 (0.21-0.56)
<0.0001
61.9
37.5
0.64 (0.45-0.89)
0.0079
54.3
31.4
0.59 (0.44-0.79)
0.0003
52.2
30.4
0.48 (0.31-0.76)
0.0011
OS
   Median, months
-
-
0.50 (0.27-0.90)
0.0179
-
-
0.64 (0.43-0.96)
0.0274
-
-
0.75 (0.55-1.02)
0.0671
-
-
0.71 (0.44-1.14)
0.1574
Abbreviations: CI, confidence interval; D-Rd, DARZALEX + lenalidomide + dexamethasone; HR, hazard ratio; NR, not reachable; OS, overall survival; Rd, lenalidomide + dexamethasone.
Safety
  • At clinical cutoff, 52 patients from the D-Rd arm discontinued lenalidomide ± dexamethasone but remained on the rest of the study treatment; 46 (88.5%) of these patients discontinued due to AEs.3
    • The median time to lenalidomide discontinuation was 37.8 months (range, 1-70).
    • The median duration of DARZALEX treatment was 66.2 months (range, 56-77).
    • The estimated 60-month PFS and OS rates were 98.1% and 100.0%, respectively.
    • Of the aforementioned 52 patients, 13 (25.0%) discontinued lenalidomide but continued DARZALEX + dexamethasone and 39 (75.0%) discontinued lenalidomide + dexamethasone and continued DARZALEX monotherapy.
      • In the 39 patients who discontinued lenalidomide + dexamethasone and continued DARZALEX monotherapy, the median time to discontinuation was 39.1 months (range, 3-67) and the median DARZALEX treatment duration was 65.6 months (range, 56-73). The estimated 60-month PFS and OS rates were 97.4% and 100.0%, respectively.
      • One patient in the D-Rd arm stopped DARZALEX after 15 days due to AEs but continued lenalidomide treatment without progression at the clinical cutoff.
  • No new safety concerns were observed with a longer follow-up.3
    • Grade 3/4 TEAEs occurred in 95.9% vs 88.8% of patients from the D-Rd vs Rd arm, respectively.
    • Grade 3/4 infections occurred in 42.6% vs 29.6% of patients from the D-Rd vs Rd arm, respectively.
    • Serious TEAEs occurred in 78.8% vs 71.0% of patients from the D-Rd vs Rd arm, respectively, with pneumonia being the most common serious TEAE (18.7% vs 10.7%, respectively).
      • Among patients aged ≥75 years, serious TEAEs occurred in 80.9% vs 79.2% of patients from the D-Rd vs Rd arm, respectively, with pneumonia being the most common serious TEAE (19.7% vs 12.6%, respectively).
      • Among patients aged ≥80 years, serious TEAEs occurred in 81.5% vs 82.9% of patients from the D-Rd vs Rd arm, respectively, with pneumonia being the most common serious TEAE (24.6% vs 8.6%, respectively).
    • The overall discontinuation rate due to TEAEs was lower in the D-Rd vs Rd arm (14.6% vs 23.8%).
      • Discontinuation of lenalidomide due to TEAEs was reported in 36.8% vs 24.4% of patients from the D-Rd vs Rd arm, respectively.
      • Discontinuation of dexamethasone due to TEAEs was reported in 39.8% vs 36.2% of patients from the D-Rd vs Rd arm, respectively.
      • Discontinuation of DARZALEX due to TEAEs was reported in 14.6% of patients.
      • Among patients aged ≥75 years, treatment discontinuation due to TEAEs was reported in 15.3% vs 27.7% of patients from the D-Rd vs Rd arm, respectively.
      • Among patients aged ≥80 years, treatment discontinuation due to TEAEs was reported in 6.2% vs 20.0% of patients from the D-Rd vs Rd arm, respectively.
    • TEAEs leading to death were reported in 9.9% vs 9.3% of patients from the D-Rd vs Rd arm, respectively.
      • Among patients aged ≥75 years, TEAEs leading to death were reported in 11.5% vs 13.2% of patients from the D-Rd vs Rd arm, respectively.
      • Among patients aged ≥80 years, TEAEs leading to death were reported in 12.3% vs 11.4% of patients from the D-Rd vs Rd arm, respectively.

Most Common Any-Grade or Grade 3/4 TEAEs in the Safety Populationa,3
TEAE, n (%)
D-Rd (n=364)
Rd (n=365)
Any Grade
Grade 3/4
Any Grade
Grade 3/4
Hematologic
   Neutropenia
224 (61.5)
197 (54.1)
166 (45.5)
135 (37.0)
   Anemia
154 (42.3)
62 (17.0)
150 (41.1)
79 (21.6)
Nonhematologic
   Diarrhea
240 (65.9)
33 (9.1)
188 (51.5)
22 (6.0)
   Fatigue
164 (45.1)
33 (9.1)
114 (31.2)
17 (4.7)
   Constipation
157 (43.1)
6 (1.6)
137 (37.5)
2 (0.5)
   Peripheral edema
155 (42.6)
10 (2.7)
117 (32.1)
3 (0.8)
   Back pain
155 (42.6)
14 (3.8)
109 (29.9)
14 (3.8)
   Asthenia
136 (37.4)
19 (5.2)
101 (27.7)
18 (4.9)
   Nausea
133 (36.5)
7 (1.9)
88 (24.1)
2 (0.5)
   Insomnia
125 (34.3)
11 (3.0)
116 (31.8)
14 (3.8)
   Bronchitis
124 (34.1)
12 (3.3)
87 (23.8)
7 (1.9)
   Cough
123 (33.8)
2 (0.5)
65 (17.8)
0 (0.0)
   Dyspnea
119 (32.7)
12 (3.3)
63 (17.3)
4 (1.1)
   Pneumonia
113 (31.0)
71 (19.5)
66 (18.1)
39 (10.7)
   Weight decreased
112 (30.8)
10 (2.7)
69 (18.9)
11 (3.0)
   Peripheral sensory neuropathy
111 (30.5)
9 (2.5)
66 (18.1)
2 (0.5)
   Muscle spasms
111 (30.5)
2 (0.5)
86 (23.6)
5 (1.4)
Abbreviations: D-Rd, DARZALEX + lenalidomide + dexamethasone; Rd, lenalidomide + dexamethasone; TEAE, treatment-emergent adverse event.
aAny-grade TEAEs that are listed are those that occurred in ≥30% of patients in either group.

Most Common Any-Grade or Grade 3/4 TEAEs Among Patients Aged ≥75 Years and ≥80 Years in the Safety Populationa,4
TEAE, n (%)
Patients Aged ≥75 years
Patients Aged ≥80 years
D-Rd (n=157)
Rd (n=159)
D-Rd (n=65)
Rd (n=70)
Any Grade
Grade 3/4
Any Grade
Grade 3/4
Any Grade
Grade 3/4
Any Grade
Grade 3/4
Hematologic
   Neutropenia
109 (69.4)
98
(62.4)
81
(50.9)
66
(41.5)
45
(69.2)
37
(56.9)
34
(48.6)
26
(37.1)
   Anemia
71 (45.2)
32 (20.4)
73 (45.9)
40 (25.2)
31 (47.7)
12 (18.5)
35 (50.0)
19 (27.1)
   Thrombocytopenia
39 (24.8)
16 (10.2)
43 (27.0)
19 (11.9)
21 (32.3)
7 (10.8)
20 (28.6)
8 (11.4)
   Lymphopenia
37 (23.6)
33 (21.0)
25 (15.7)
20 (12.6)
10 (15.4)
8 (12.3)
13 (18.6)
10 (14.3)
Nonhematologic
   Diarrhea
98 (62.4)
16 (10.2)
80 (50.3)
8 (5.0)
37 (56.9)
5 (7.7)
35 (50.0)
3 (4.3)
   Peripheral edema
76 (48.4)
6 (3.8)
53 (33.3)
2 (1.3)
31 (47.7)
0 (0.0)
24 (34.3)
2 (2.9)
   Constipation
75 (47.8)
2 (1.3)
61 (38.4)
1 (0.6)
27 (41.5)
0 (0.0)
27 (38.6)
1 (1.4)
   Fatigue
73 (46.5)
15 (9.6)
48 (30.2)
8 (5.0)
26 (40.0)
7 (10.8)
19 (27.1)
3 (4.3)
   Back pain
65 (41.4)
7 (4.5)
53 (33.3)
6 (3.8)
24 (36.9)
2 (3.1)
21 (30.0)
2 (2.9)
   Asthenia
58 (36.9)
8 (5.1)
43 (27.0)
10 (6.3)
25 (38.5)
3 (4.6)
26 (37.1)
8 (11.4)
   Weight decreased
49 (31.2)
6 (3.8)
31 (19.5)
5 (3.1)
19 (29.2)
2 (3.1)
16 (22.9)
2 (2.9)
   Bronchitis
48 (30.6)
7 (4.5)
31 (19.5)
4 (2.5)
18 (27.7)
2 (3.1)
15 (21.4)
1 (1.4)
   Nausea
48 (30.6)
2 (1.3)
40 (25.2)
0 (0.0)
21 (32.3)
1 (1.5)
20 (28.6)
0 (0.0)
   Pneumonia
44 (28.0)
32 (20.4)
33 (20.8)
23 (14.5)
22 (33.8)
17 (26.2)
13 (18.6)
8 (11.4)
   Pyrexia
44 (28.0)
6 (3.8)
22 (13.8)
3 (1.9)
20 (30.8)
4 (6.2)
7 (10.0)
0 (0.0)
Abbreviations: D-Rd, DARZALEX + lenalidomide + dexamethasone; Rd, lenalidomide + dexamethasone; TEAE, treatment-emergent adverse event.
aAny-grade TEAEs that are listed are those that occurred in ≥30% of patients in either group.

Final Survival Analysis of the MAIA Study

Facon et al (2024)5 presented the updated OS results for the D-Rd vs Rd arm at a long-term median follow-up of around 7.5 years.

Results

Patient Characteristics
Efficacy
  • At a median follow-up of 89.3 months (range, 0-102.2), the 7-year OS rate was 53.1% for the D-Rd arm and 39.3% for the Rd arm.
  • Median OS was reached for the D-Rd group and was prolonged for patients in the D-Rd vs Rd arm (90.3 vs 64.1 months [HR, 0.67; 95% CI, 0.55-0.82; nominal P<0.0001]). See Table: Analysis of OS in Pre-Specified Patient Subgroups.
  • Median time to subsequent antimyeloma therapy was 42.4 months in the Rd arm and NR in the D-Rd arm (HR, 0.51; 95% CI, 0.41-0.63; nominal P<0.0001). See Table: Summary of First Subsequent Antimyeloma Therapy in the Safety Population.
    • In the D-Rd vs Rd arm, 10.7% (15/140) vs 24.4% (49/201) of patients received DARZALEX-containing regimens as their first subsequent therapy.
    • Among treated patients, 38.5% (140/364) vs 55.1% (201/365) of patients in the D-Rd vs Rd arm received ≥1 subsequent antimyeloma therapy.
    • Across subsequent therapy lines, the most common antineoplastic agents in the D-Rd vs Rd arms were bortezomib (27.7% vs 41.9%), DARZALEX (6.3% vs 28.8%), and carfilzomib (7.7% vs 12.3%).
    • In patients evaluable for best response to first subsequent antimyeloma therapy, ≥CR was achieved by 4.6% (6/130) vs 4.1% (8/193) in the D-Rd vs Rd arm, and ≥VGPR was achieved by 13.8% (18/130) vs 23.8% (46/193) of patients in the D-Rd vs Rd arm.
    • No patient in either group reported the use of B-cell maturation antigen (BCMA)- or G protein-coupled receptor class C group 5 member D (GPRC5D)-targeted therapy.
    • Investigational drug was given to 2 patients in the D-Rd group and 2 patients in the Rd group in subsequent therapy lines.

Analysis of OS in Pre-Specified Patient Subgroupsa,5
Subgroup
D-Rd
Rd
HR (95% CI)b
n/N
Median OS, Months
n/N
Median OS, Months
Sex
   Male
95/189
82.5
120/195
60.6
0.72 (0.55-0.94)
   Female
80/179
NE
98/174
67.8
0.66 (0.49-0.89)
Age
   <75 years
84/208
NE
107/208
79.6
0.69 (0.52-0.92)
   ≥75 years
91/160
72.3
111/161
54.8
0.67 (0.51-0.88)
Race
   White
161/336
92.7
197/339
65.5
0.71 (0.57-0.87)
   Other
14/32
90.3
21/30
49.1
0.50 (0.25-0.99)
Region
   North America
46/101
92.7
64/102
54.8
0.57 (0.39-0.83)
   Other
129/267
90.3
154/267
66.8
0.74 (0.58-0.93)
Baseline renal function (CrCl)
   >60 mL/min
99/206
92.7
123/227
69.9
0.78 (0.60-1.01)
   ≤60 mL/min
76/162
90.3
95/142
54.4
0.57 (0.42-0.77)
Baseline hepatic function
   Normal
156/335
NE
203/340
63.8
0.65 (0.53-0.80)
   Impaired
19/31
63.5
15/29
87.4
1.31 (0.66-2.58)
ISS disease stage
   I
34/98
NE
42/103
NE
0.79 (0.50-1.24)
   II
77/163
92.7
95/156
61.7
0.63 (0.46-0.85)
   III
64/107
65.2
81/110
47.3
0.68 (0.49-0.95)
Type of MM
   IgG
111/225
87.2
132/231
69.3
0.78 (0.60-1.00)
   Non-IgG
35/74
86.4
49/76
53.7
0.58 (0.37-0.89)
Cytogenetic risk at study entryc
   High risk
31/48
55.6
36/44
42.5
0.65 (0.40-1.06)
   Standard risk
122/271
NE
160/279
65.5
0.66 (0.52-0.84)
ECOG PS
   0
48/127
NE
56/123
NE
0.76 (0.52-1.12)
   1
86/178
92.7
118/187
58.3
0.64 (0.48-0.84)
   ≥2
41/63
62.8
44/59
39.0
0.68 (0.44-1.04)
Abbreviations: CI, confidence interval; CrCl, creatinine clearance; del, deletion; D-Rd, DARZALEX + lenalidomide + dexamethasone; ECOG PS, Eastern Cooperative Oncology Group performance status; HR, hazard ratio; IgG, immunoglobulin G; ISS, International Staging System; MM, multiple myeloma; NE, not estimable; OS, overall survival; Rd, lenalidomide + dexamethasone; t, translocation.
aIn the ITT population, which included all randomized patients.
bHR and 95% CI from a Cox proportional hazards model with treatment as the sole explanatory variable. HR <1 indicates an advantage for D-Rd.
cCytogenetic risk was based on fluorescence in situ hybridization or karyotype analysis; patients who had a high-risk cytogenetic profile had ≥1 of the following high-risk abnormalities: del(17p), t(14;16), or t(4;14).

Summary of First Subsequent Antimyeloma Therapy in the Safety Populationa,5
n (%)
D-Rd
(n=140)
Rd
(n=201)
First subsequent therapy classb,c
   PI only
69 (49.3)
101 (50.2)
   IMiD only
22 (15.7)
25 (12.4)
   PI + IMiD
25 (17.9)
16 (8.0)
   DARZALEX monotherapy or combination
15 (10.7)
49 (24.4)
   Other
9 (6.4)
10 (5.0)
Most common first subsequent therapy regimensb,d
   Bortezomib/cyclophosphamide/dexamethasone
19 (13.6)
29 (14.4)
   Bortezomib/dexamethasone
20 (14.3)
28 (13.9)
   Bortezomib/melphalan/prednisone
14 (10.0)
28 (13.9)
   DARZALEX/bortezomib/dexamethasone
4 (2.9)
27 (13.4)
   Lenalidomide/dexamethasone
13 (9.3)
16 (8.0)
   Bortezomib/pomalidomide/dexamethasone
9 (6.4)
3 (1.5)
   Bortezomib/lenalidomide/dexamethasone
8 (5.7)
3 (1.5)
   DARZALEX/lenalidomide/dexamethasone
4 (2.9)
6 (3.0)
   Pomalidomide/dexamethasone
2 (1.4)
6 (3.0)
Abbreviations: D-Rd, DARZALEX + lenalidomide + dexamethasone; IMiD, immunomodulatory drugs; PI, proteasome inhibitor; Rd, lenalidomide + dexamethasone.
aThe safety population included all randomized patients who received ≥1 dose of study treatment.
bPercentages were calculated with the number of patients who received subsequent therapy in each treatment group as the denominator.
cTherapy classes are mutually exclusive. Patients in any therapy class subgroup may have received additional agents (other than PI, IMiD, or DARZALEX), such as dexamethasone.
dRegimens received by ≥3% of patients in either treatment group.
Safety and Tolerability
  • Among the safety population, 78.3% (n=285) of patients in the D-Rd arm and 94.5% (n=345) in the Rd arm discontinued study treatment.
    • PD was the primary reason for discontinuation in both the D-Rd (32.7%) and Rd arms (38.6%).
    • A lower proportion of patients in the D-Rd (16.5%) and Rd arms (25.8%) discontinued study treatment due to AEs.
  • In the D-Rd vs Rd arm, 33% reduction in the risk of death was reported.

Summary of Death and Causes of Death in the Safety Populationa,5
n (%)
D-Rd
(n=364)
Rd
(n=365)
Total number of patients who died during the study
173 (47.5)
218 (59.7)
   Primary cause of death
      Disease progression
76 (20.9)
88 (24.1)
      Adverse events
44 (12.1)
40 (11.0)
         Related to study treatmentb
14 (3.8)
10 (2.7)
         Unrelated to study treatment
28 (7.7)
29 (7.9)
         Othersc
53 (14.6)
90 (24.7)
         Infections/infestations
9 (2.5)
30 (8.2)
         General disorders/administration site conditionsd
11 (3.0)
5 (1.4)
         Neoplasms (benign, malignant, or unspecified)
11 (3.0)
4 (1.1)
         Cardiac disorders
1 (0.3)
8 (2.2)
         Nervous system disorders
3 (0.8)
5 (1.4)
         Unknown
13 (3.6)
27 (7.4)
Deaths within 30 days of last study treatment dose
31 (8.5)
35 (9.6)
   Primary cause of death
      Disease progression
1 (0.3)
1 (0.3)
      Adverse events
29 (8.0)
32 (8.8)
         Related to study treatmentb
11 (3.0)
10 (2.7)
         Unrelated to study treatment
18 (4.9)
22 (6.0)
         Othere
1 (0.3)
2 (0.5)
Abbreviations: D-Rd, DARZALEX + lenalidomide + dexamethasone; Rd, lenalidomide/dexamethasone.
aThe safety population included all randomized patients who received ≥1 dose of study treatment.
bAdverse events were related to ≥1 of the 3 components of study treatment: DARZALEX, lenalidomide, and dexamethasone.
cOther reasons were reported in ≥1% of patients in either treatment group.
dAll events were related to the general health condition of the patient.
eIncludes a nervous system disorder in 1 patient in the D-Rd group and a blood and lymphatic system disorder and general disorder/administration site condition in 1 patient each in the Rd group.

Analysis of Clinically Important Subgroups of MAIA

Moreau et al (2025)6 presented the efficacy and safety results in clinically important subgroups of patients from the MAIA study.

Study Design/Methods

  • Efficacy outcomes (PFS, ORR, and MRD-negativity) were analyzed in subgroups based on the following patient characteristics:
    • Age ≥75 years
    • Frail (based on the simplified frailty score, which was assessed retrospectively using age, baseline ECOG PS, and Charlson comorbidity index)
    • International Staging System (ISS) stage III disease
    • Revised ISS stage III disease
    • Renal insufficiency (baseline CrCl ≤60 mL/min)
    • Extramedullary plasmacytomas
    • Cytogenetic risk
      • Presence of HRCAs (t[4;14], t[14;16], and/or del[17p]) or a high serum lactate dehydrogenase level
      • Standard cytogenetic risk (0 of the following HRCAs: t[4;14], t[14;16], and del[17p])
      • High cytogenetic risk (≥1 of the following HRCAs: t[4;14], t[14;16], and del[17p])
      • Revised standard cytogenetic risk (0 of the following HRCAs: t[4;14], t[14;16], del[17p], t[14;20], gain[1q21], and amp[1q21])
      • Revised high cytogenetic risk (≥1 of the following HRCAs: t[4;14], t[14;16], del[17p], t[14;20], gain[1q21], and amp[1q21])
      • Gain(1q21) (3 copies of chromosome 1q21, with or without other HRCAs)
      • Amp(1q21) (≥4 copies of chromosome 1q21, with or without other HRCAs)
      • Gain(1q21) or amp(1q21) (3 or ≥4 copies of chromosome 1q21, with or without other HRCAs)
      • 1 HRCA (only 1 of the following HRCAs: t[4;14], t[14;16], del[17p], t[14;20], gain[1q21], or amp[1q21])
      • Two or more HRCAs (≥2 of the following HRCAs: t[4;14], t[14;16], del[17p], t[14;20], gain[1q21], and amp[1q21])
      • Isolated gain(1q21) (3 copies of chromosome 1q21, without any other HRCAs)
      • Isolated amp(1q21) (≥4 copies of chromosome 1q21, without any other HRCAs)
      • Isolated gain(1q21) or amp(1q21) (3 or ≥4 copies of chromosome 1q21, without any other HRCAs)
      • Gain(1q21) or amp(1q21) plus ≥1 HRCA (3 or ≥4 copies of chromosome 1q21, plus ≥1 of the following HRCAs: t[4;14], t[14;16], del[17p], and t[14;20])

Results

Patient Characteristics
  • Overall, 737 patients (D-Rd, 368; Rd, 369) were included in the ITT population.
  • The median follow-up was 64.5 months.
Efficacy

Subgroup Analysis of PFS in the ITT Population of MAIA6
Subgroup
D-Rd
Rd
HR (95% CI)a
n/N
Median PFS, Month
n/N
Median PFS, Month
ITT (overall)
176/368
61.9
228/369
34.4
0.55 (0.45-0.67)
Patient characteristics
   Age ≥75 years
87/160
54.3
106/161
31.4
0.59 (0.44-0.79)
   Frail
92/172
52.2
106/169
30.4
0.64 (0.48-0.85)
   Renal insufficiency
82/162
56.7
92/142
29.7
0.55 (0.41-0.75)
Disease-related characteristics
   ISS stage III
61/107
42.4
73/110
24.2
0.61 (0.43-0.86)
   Revised ISS stage III
26/43
40.0
29/40
17.9
0.56 (0.33-0.97)
   Extramedullary
   plasmacytomas
7/15
57.5
5/9
19.4
0.47 (0.15-1.50)
Cytogenetic risk
      Standard cytogenetic
      risk
126/271
63.8
174/279
34.4
0.51 (0.41-0.64)
      High cytogenetic risk
28/48
45.3
31/44
29.6
0.57 (0.34-0.96)
      Revised standard
      cytogenetic risk
78/176
NR
115/187
35.1
0.50 (0.37-0.66)
      Revised high
      cytogenetic risk
82/156
56.0
96/152
30.7
0.59 (0.44-0.80)
      Gain(1q21)
20/53
NR
28/44
37.8
0.43 (0.24-0.76)
      Amp(1q21)
48/74
40.0
45/76
26.1
0.81 (0.54-1.21)
      Gain(1q21) or
      amp(1q21)
68/127
53.2
73/120
32.3
0.63 (0.46-0.88)
      1 HRCA
68/137
61.4
86/137
31.2
0.55 (0.40-0.76)
      ≥2 HRCAs
14/19
24.9
10/15
24.0
0.92 (0.40-2.10)
      Isolated gain(1q21)
16/47
NR
27/42
37.8
0.36 (0.19-0.67)
      Isolated amp(1q21)
38/61
42.8
38/65
28.9
0.78 (0.50-1.22)
      Isolated gain(1q21) or
      amp(1q21)
54/108
61.4
65/107
37.1
0.58 (0.40-0.83)
      Gain(1q21) or
      amp(1q21) plus ≥1
      HRCA
14/19
24.9
8/13
24.0
1.03 (0.42-2.48)
Abbreviations: CI, confidence interval; D-Rd, DARZALEX + lenalidomide + dexamethasone; HR, hazard ratio; HRCA, high-risk cytogenetic abnormality; ISS, International Staging System; ITT, intent-to-treat; NR, not reached; PFS, progression-free survival; Rd, lenalidomide + dexamethasone.
aHR <1 indicates an advantage for D-Rd.

Subgroup Analysis of ORR in the ITT Population of MAIA6
Subgroup
D-Rd
n/N (%)
Rd
n/N (%)
OR (95% CI)a
ITT (overall)
342/368 (92.9)
301/369 (81.6)
2.97 (1.84-4.79)
Patient characteristics
   Age ≥75 years
144/160 (90.0)
131/161 (81.4)
2.06 (1.07-3.95)
   Frail
150/172 (87.2)
132/169 (78.1)
1.91 (1.07-3.40)
   Renal insufficiency
146/162 (90.1)
112/142 (78.9)
2.44 (1.27-4.70)
Disease-related characteristics
   ISS stage III
93/107 (86.9)
86/110 (78.2)
1.85 (0.90-3.81)
   Revised ISS stage III
36/43 (83.7)
28/40 (70.0)
2.20 (0.77-6.33)
   Extramedullary plasmacytomas
13/15 (86.7)
3/9 (33.3)
13.00 (1.70-99.37)
Cytogenetic risk
      Standard cytogenetic risk
253/271 (93.4)
228/279 (81.7)
3.14 (1.78-5.54)
      High cytogenetic risk
44/48 (91.7)
33/44 (75.0)
3.67 (1.07-12.55)
      Revised standard cytogenetic risk
162/176 (92.0)
149/187 (79.7)
2.95 (1.54-5.66)
      Revised high cytogenetic risk
147/156 (94.2)
126/152 (82.9)
3.37 (1.52-7.46)
      Gain(1q21)
51/53 (96.2)
39/44 (88.6)
3.27 (0.60-17.75)
      Amp(1q21)
70/74 (94.6)
63/76 (82.9)
3.61 (1.12-11.65)
      Gain(1q21) or amp(1q21)
121/127 (95.3)
102/120 (85.0)
3.56 (1.36-9.30)
      1 HRCA
129/137 (94.2)
114/137 (83.2)
3.25 (1.40-7.56)
      ≥2 HRCAs
18/19 (94.7)
12/15 (80.0)
4.50 (0.42-48.53)
      Isolated gain(1q21)
46/47 (97.9)
37/42 (88.1)
6.22 (0.70-55.56)
      Isolated amp(1q21)
57/61 (93.4)
55/65 (84.6)
2.59 (0.77-8.75)
      Isolated gain(1q21) or amp(1q21)
103/108 (95.4)
92/107 (86.0)
3.36 (1.17-9.60)
      Gain(1q21) or amp(1q21) plus
      ≥1HRCA
18/19 (94.7)
10/13 (76.9)
5.40 (0.49-59.02)
Abbreviations: CI, confidence interval; D-Rd, DARZALEX + lenalidomide + dexamethasone; HRCA, high-risk cytogenetic abnormality; ISS, International Staging System; ITT, intent-to-treat; OR, odds ratio; ORR, overall response rate; Rd, lenalidomide + dexamethasone.
aOR >1 indicates an advantage for D-Rd.

Subgroup Analysis of MRD-Negativity (10-5) Rates in the ITT Population of MAIA6
Subgroup
D-Rd
n/N (%)
Rd
n/N (%)
OR (95% CI)a
ITT (overall)
118/368 (32.1)
41/369 (11.1)
3.78 (2.55-5.59)
Patient characteristics
   Age ≥75 years
43/160 (26.9)
16/161 (9.9)
3.33 (1.79-6.21)
   Frail
44/172 (25.6)
22/169 (13.0)
2.30 (1.31-4.04)
   Renal insufficiency
48/162 (29.6)
11/142 (7.7)
5.01 (2.49-10.11)
Disease-related characteristics
   ISS stage III
29/107 (27.1)
12/110 (10.9)
3.04 (1.46-6.34)
   Revised ISS stage III
13/43 (30.2)
3/40 (7.5)
5.34 (1.39-20.50)
   Extramedullary plasmacytomas
5/15 (33.3)
0/9 (0)
NE (NE-NE)
Cytogenetic risk
      Standard cytogenetic risk
93/271 (34.3)
33/279 (11.8)
3.89 (2.50-6.06)
      High cytogenetic risk
12/48 (25.0)
1/44 (2.3)
14.33 (1.78-115.59)
      Revised standard cytogenetic risk
60/176 (34.1)
21/187 (11.2)
4.09 (2.36-7.09)
      Revised high cytogenetic risk
49/156 (31.4)
15/152 (9.9)
4.18 (2.22-7.86)
      Gain(1q21)
19/53 (35.8)
6/44 (13.6)
3.54 (1.27-9.89)
      Amp(1q21)
23/74 (31.1)
8/76 (10.5)
3.83 (1.59-9.27)
      Gain(1q21) or amp(1q21)
42/127 (33.1)
14/120 (11.7)
3.74 (1.92-7.30)
      1 HRCA
44/137 (32.1)
15/137 (10.9)
3.85 (2.02-7.34)
      ≥2 HRCAs
5/19 (26.3)
0/15 (0)
NE (NE-NE)
      Isolated gain(1q21)
17/47 (36.2)
6/42 (14.3)
3.40 (1.19-9.71)
      Isolated amp(1q21)
20/61 (32.8)
8/65 (12.3)
3.48 (1.39-8.66)
      Isolated gain(1q21) or amp(1q21)
37/108 (34.3)
14/107 (13.1)
3.46 (1.74-6.89)
      Gain(1q21) or amp(1q21) plus
      ≥1 HRCA
5/19 (26.3)
0/13 (0)
NE (NE-NE)
Abbreviations: CI, confidence interval; D-Rd, DARZALEX + lenalidomide + dexamethasone; HRCA, high-risk cytogenetic abnormality; ISS, International Staging System; ITT, intent-to-treat; MRD, minimal residual disease; NE, not evaluable; OR, odds ratio; Rd, lenalidomide + dexamethasone.
aOR >1 indicates an advantage for D-Rd.

Subgroup Analysis of Rates of Sustained MRD-Negativity (10-5) Lasting ≥12 Months in the ITT Population6
Subgroup
D-Rd
n/N (%)
Rd
n/N (%)
OR (95% CI)a
ITT (overall)
69/368 (18.8)
15/369 (4.1)
5.45 (3.05-9.72)
Patient characteristics
   Age ≥75 years
22/160 (13.8)
5/161 (3.1)
4.97 (1.83-13.49)
   Frail
27/172 (15.7)
7/169 (4.1)
4.31 (1.82-10.19)
   Renal insufficiency
30/162 (18.5)
2/142 (1.4)
15.91 (3.73-67.89)
Disease-related characteristics
   ISS stage III
17/107 (15.9)
3/110 (2.7)
6.74 (1.91-23.73)
   Revised ISS stage III
7/43 (16.3)
0/40 (0)
NE (NE-NE)
   Extramedullary plasmacytomas
2/15 (13.3)
0/9 (0)
NE (NE-NE)
Cytogenetic risk
      Standard cytogenetic risk
55/271 (20.3)
11/279 (3.9)
6.20 (3.17-12.14)
      High cytogenetic risk
6/48 (12.5)
0/44 (0)
NE (NE-NE)
      Revised standard cytogenetic risk
31/176 (17.6)
5/187 (2.7)
7.78 (2.95-20.52)
      Revised high cytogenetic risk
32/156 (20.5)
7/152 (4.6)
5.35 (2.28-12.53)
      Gain(1q21)
14/53 (26.4)
3/44 (6.8)
4.91 (1.31-18.40)
      Amp(1q21)
13/74 (17.6)
4/76 (5.3)
3.84 (1.19-12.38)
      Gain(1q21) or amp(1q21)
27/127 (21.3)
7/120 (5.8)
4.36 (1.82-10.44)
      1 HRCA
31/137 (22.6)
7/137 (5.1)
5.43 (2.30-12.83)
      ≥2 HRCAs
1/19 (5.3)
0/15 (0)
NE (NE-NE)
      Isolated gain(1q21)
14/47 (29.8)
3/42 (7.1)
5.52 (1.46-20.86)
      Isolated amp(1q21)
12/61 (19.7)
4/65 (6.2)
3.73 (1.13-12.31)
      Isolated gain(1q21) or amp(1q21)
26/108 (24.1)
7/107 (6.5)
4.53 (1.87-10.97)
      Gain(1q21) or amp(1q21) plus ≥1 HRCA
1/19 (5.3)
0/13 (0)
NE (NE-NE)
Abbreviations: CI, confidence interval; D-Rd, DARZALEX + lenalidomide + dexamethasone; HRCA, high-risk cytogenetic abnormality; ISS, International Staging System; ITT, intent-to-treat; MRD, minimal residual disease; NE, not evaluable; OR, odds ratio; Rd, lenalidomide + dexamethasone.
aOR >1 indicates an advantage for D-Rd.
Safety (Patients Aged ≥75 Years)
  • Among patients aged ≥75 years, grade 3/4 TEAEs were reported in 95.5% vs 95.0% patients in the D-Rd vs Rd arm.
  • Serious TEAEs were reported in 80.9% vs 79.2% of patients in the D-Rd vs Rd arm, the most common of which was pneumonia (D-Rd, 19.7%; Rd, 12.6%).
  • TEAEs led to treatment discontinuation in 15.3% vs 27.7% of patients in the D-Rd vs Rd arm.
  • TEAEs resulting in death were reported in 11.5% vs 13.2% of patients in the D-Rd vs Rd arm.

Most Common (≥10%) Grade 3/4 TEAEs Among Patients Aged ≥75 Years in the Safety Population6
Grade 3/4 TEAE, n (%)
D-Rd
(n=157)
Rd
(n=159)
Neutropenia
98 (62.4)
66 (41.5)
Lymphopenia
33 (21.0)
20 (12.6)
Anemia
32 (20.4)
40 (25.2)
Pneumonia
32 (20.4)
23 (14.5)
Leukopenia
19 (12.1)
12 (7.5)
Hypokalemia
18 (11.5)
17 (10.7)
Hypertension
17 (10.8)
8 (5.0)
Thrombocytopenia
16 (10.2)
19 (11.9)
Diarrhea
16 (10.2)
8 (5.0)
Abbreviations: D-Rd, DARZALEX + lenalidomide + dexamethasone; Rd, lenalidomide + dexamethasone; TEAE, treatment-emergent adverse event.

Post Hoc Analysis of MAIA Study

Moreau et al (2022)7 analyzed PFS and OS by treatment duration within the MAIA study, with a median follow-up of 56.2 months.

Study Design/Methods

  • OS was evaluated in patients who received treatment with D-Rd for <18 months and ≥18 months.
  • PFS and OS was evaluated in the following subgroups:
    • Patients who received treatment with D-Rd and who discontinued either DARZALEX only or lenalidomide only with or without dexamethasone but continued remaining treatment.
    • Patients who received treatment with D-Rd or Rd for ≥9 months or for ≥18 months.
    • Patients who achieved VGPR by 6 months and ≥CR by 9 months or 18 months.
  • Patients were excluded from this analysis if the treatment with D-Rd was discontinued due to disease progression during the first 18 months.

Results


Baseline Characteristics and Demographics7
Characteristic, n (%)
ITT Population (D-Rd, n=368)
Discontinued only R±da
(D-Rd, n=48)
D-Rd treatment
<18 monthsb
(n=48)
D-Rd treatment ≥18 monthsb (n=283)
Age
   <65 years
4 (1.1)
0
3 (6.3)
1 (0.4)
   65-74 years
204 (55.4)
26 (54.2)
18 (37.5)
167 (59.0)
   ≥75 years
160 (43.5)
22 (45.8)
27 (56.3)
115 (40.6)
   Median (range)
73.0 (50-90)
74.0 (67-87)
75.0 (50-90)
73.0 (55-88)
Baseline ECOG PS score
   0
127 (34.5)
15 (31.3)
10 (20.8)
110 (38.9)
   1
178 (48.4)
25 (52.1)
25 (52.1)
132 (46.6)
   ≥2
63 (17.1)
8 (16.7)
13 (27.1)
41 (14.5)
ISS disease stagec
   I
98 (26.6)
14 (29.2)
8 (16.7)
84 (29.7)
   II
163 (44.3)
26 (54.2)
19 (39.6)
129 (45.6)
   III
107 (29.1)
8 (16.7)
21 (43.8)
70 (24.7)
Cytogenetic abnormalitiesd
   N
319
45
44
242
      Standard risk
271 (85.0)
39 (86.7)
38 (86.4)
212 (87.6)
      High risk
48 (15.0)
6 (13.3)
6 (13.6)
30 (12.4)
Frailty status
   Frail
172 (46.7)
23 (47.9)
30 (62.5)
118 (41.7)
   Intermediate
128 (34.8)
19 (39.6)
13 (27.1)
105 (37.1)
   Fit
68 (18.5)
6 (12.5)
5 (10.4)
60 (21.2)
Abbreviations: D-Rd, DARZALEX + lenalidomide + dexamethasone; ECOG PS, Eastern Cooperative Oncology Group performance status; ISS, International Staging System; ITT, intention-to-treat; R±d, lenalidomide ± dexamethasone.
aPatients discontinued R±d but continued remaining treatment.
bPatients who discontinued D-Rd due to disease progression during the first 18 months of treatment were excluded.
cISS staging is derived based on the combination of serum β2-microglobulin and albumin.
dCytogenetic abnormalities (del17p, t[14;16] or t[4;14]) were based on fluorescence in situ hybridization or karyotype testing. Percentages calculated with the number of patients in each treatment group as the denominator).
Patient Disposition

Reasons for Lenalidomide Discontinuation 7
Event, n (%)
Discontinued only R±d
(D-Rd, n=48)a
Reasons for lenalidomide discontinuation
   Adverse Event
44 (91.7)
   Otherb
4 (8.3)
Most common (≥5%) reasons for discontinuation of lenalidomide due to adverse events
   Diarrhea
9 (18.8)
   Peripheral sensory neuropathy
5 (10.4)
   Neutropenia
4 (8.3)
   Constipation
6 (6.3)
Abbreviations: D-Rd, DARZALEX + lenalidomide + dexamethasone; R±d, lenalidomide ± dexamethasone.
aPatients discontinued R±d but continued remaining treatment.
bOther includes patient decision to discontinue, interruption due to adverse events caused by progressive disease or other conditions, or cumulative low-grade adverse events.
Efficacy
  • Median duration of DARZALEX treatment in the D-Rd arm was 58.1 months in patients who discontinued R±d but continued remaining treatment.
    • The estimated 60-month PFS rate and OS rate was 97.9% and 100.0%, respectively.
  • Only 1 patient discontinued DARZALEX while continuing lenalidomide treatment.
    • This patient was alive and progression free at the time of analysis. No further analysis was performed on this patient.
  • The median OS in the D-Rd arm was NR vs 20.5 months (HR, 0.16; 95% CI, 0.1-0.25; P<0.0001) in patients who received treatment for ≥18 months vs <18 months, respectively.
  • In patients who received D-Rd vs Rd for ≥9 months, PFS (HR, 0.49; 95% CI, 0.38-0.62; P<0.0001) and OS (HR, 0.63; 95% CI, 0.47-0.85; P=0.0025) benefits were observed.
  • PFS benefit in the D-Rd vs Rd arm was observed in patients who received treatment for ≥18 months (HR, 0.57; 95% CI, 0.43-0.76; P<0.0001) vs ITT population (HR, 0.53; 95% CI, 0.43-0.66; P<0.0001).
  • OS benefit in the D-Rd vs Rd arm was observed in patients who received treatment for ≥18 months (HR, 0.68; 95% CI, 0.47-0.98; P=0.0379) vs ITT population (HR, 0.68; 95% CI, 0.53-0.86; P=0.0013).
  • PFS and OS benefits in the D-Rd vs Rd arm was observed in patients who achieved a best response of VGPR by 6 months and converted to ≥CR by 9 or 18 months as presented in Table: PFS and OS in Patients Who Achieved VGPR by 6 Months and Converted to ≥CR by 9 or 18 Months.
  • Among patients who were treated for ≥18 months, the ≥CR rate was 9.2% vs 4.4% at 6 months, 19.1% vs 11.3% at 9 months, and 49.8% vs 30.4% at 18 months in the D-Rd vs Rd arm, respectively. See Table: Response Rates in Patients Treated for ≥18 Months.

PFS and OS in Patients Who Achieved VGPR by 6 Months and Converted to ≥CR by 9 or 18 Months7
Parameter
D-Rd
Rd
Hazard Ratio (95% CI)
P value
Patients who achieved VGPR by 6 Months and converted to ≥CR by 9 months
   Median PFS, months
NR
38.4
0.15 (0.05-0.45)
<0.0001
   Median OS, months
NR
53.8
0.25 (0.07-0.86)
0.0175
Patients who achieved VGPR by 6 Months and converted to ≥CR by 18 months
   Median PFS, months
NR
53.6
0.34 (0.19-0.62)
0.0002
   Median OS, months
NR
NR
0.33 (0.17-0.65)
0.0006
Abbreviations: CI, confidence interval; ≥CR, complete response or better; D-Rd, DARZALEX + lenalidomide + dexamethasone; NR, not reached; OS, overall survival; PFS, progression-free survival; Rd, lenalidomide + dexamethasone; VGPR, very good partial response.

Response Rates in Patients Treated for ≥18 Months7
Response Rates, %
6 months
9 months
18 months
D-Rd
Rd
D-Rd
Rd
D-Rd
Rd
ORR
98.2
93.6
98.6
96.1
99.6
98.0
   P value
0.0079
0.0785
0.0828
≥CR
9.2
4.4
19.1
11.3
49.8
30.4
   P value
0.0443
0.0199
<0.0001
   sCR
2.5
2.9
7.1
5.4
27.2
13.7
   CR
6.7
1.5
12.0
5.9
22.6
16.7
VGPR
57.2
38.2
57.2
41.7
36.7
37.3
PR
31.8
51.0
22.3
43.1
13.1
30.4
Abbreviations: CR, complete response; D-Rd, DARZALEX + lenalidomide + dexamethasone; ORR, overall response rate; PR, partial response; Rd, lenalidomide + dexamethasone; sCR, stringent complete response; VGPR, very good partial response.
Safety

Most Common (≥10% in Either Treatment Arm) Grade 3/4 TEAEs in Patients Who Received ≥18 Months of Treatment7
Event, n (%)
D-Rd (n=283)
Rd (n=204)
≥1 grade 3/4 TEAE
273 (96.5)
186 (91.2)
Hematologic
   Neutropenia
161 (56.9)
84 (41.2)
   Anemia
48 (17.0)
37 (18.1)
   Lymphopenia
48 (17.0)
25 (12.3)
   Leukopenia
33 (11.7)
19 (9.3)
Non-Hematologic
   Pneumonia
56 (19.8)
22 (10.8)
   Hypokalemia
41 (14.5)
24 (11.8)
   Cataract
39 (13.8)
38 (18.6)
Abbreviations: D-Rd, DARZALEX + lenalidomide + dexamethasone; Rd, lenalidomide + dexamethasone;
TEAE, treatment-emergent adverse event.

Impact of Frailty on Safety and Efficacy in the MAIA Study

Facon et al (2022)8 reported a post hoc subgroup analysis of frailty status in patients with NDMM ineligible for transplant in the MAIA study.

Results

Patient Characteristics
  • Patients (D-Rd, n=368; Rd, n=369) were stratified based on frailty scores (assessed using age, Charlson comorbidity index, and baseline ECOG PS scores):
    • Frail patients: 172 (46.7%) in the D-Rd arm vs 169 (45.8%) in the Rd arm
    • Total non-frail (fit and intermediate combined) patients: 196 (53.3%) in the D-Rd arm vs 200 (54.2%) in the Rd arm
    • Intermediate patients: 128 (34.8%) in the D-Rd arm vs 122 (33.1%) in the Rd arm
    • Fit patients: 68 (18.5%) in the D-Rd arm vs 78 (21.1%) in the Rd arm
  • Median follow-up was 36.4 months.
Efficacy
  • Median relative dose intensity (RDI) of DARZALEX was consistent across all frailty subgroups (≥98.0%).
  • Median RDI of lenalidomide was higher in the D-Rd arm (77.2% vs 65.4%) and lower in the Rd arm (86.4% vs 92.9%) for patients in the total non-frail vs frail subgroup, respectively.
  • Median PFS benefit was observed in all subgroups:
    • For frail patients, PFS was NR in the D-Rd arm vs 30.4 months in the Rd arm (HR, 0.62; 95% CI, 0.45-0.85; P=0.003).
    • For total non-frail patients, PFS was NR in the D-Rd arm vs 41.7 months in the Rd arm (HR, 0.48; 95% CI, 0.34-0.68; P<0.0001).
    • For intermediate patients, PFS was NR in both the D-Rd and Rd arms (HR, 0.53; 95% CI, 0.35-0.80; P=0.0024).
    • For fit patients, PFS was NR in the D-Rd arm vs 41.7 months in the Rd arm (HR, 0.41; 95% CI, 0.22-0.75; P=0.0028).
  • The 36-month PFS rate was higher in the D-Rd vs Rd arm, respectively, in all subgroups:
    • Frail patients: 61.5% vs 39.5%
    • Total non-frail patients: 73.2% vs 52.1%
    • Intermediate patients: 70.4% vs 51.7%
    • Fit patients: 78.3% vs 53.6%
  • ORR was 87.2% vs 78.1% (P=0.0265) in frail patients, 98.0% vs 84.5% (P<0.0001) in total non-frail patients, 96.9% vs 85.2% (P=0.0012) in intermediate patients, and 100.0% vs 83.3% (P=0.0004) in fit patients receiving D-Rd vs Rd, respectively.
  • The rate of achieving ≥CR was 43.6% vs 30.8% (P=0.0144) in frail patients, 54.6% vs 24.0% (P<0.0001) in total non-frail patients, 53.9% vs 25.4% (P<0.0001) in intermediate patients, and 55.9% vs 21.8% (P<0.0001) in fit patients receiving D-Rd vs Rd, respectively.
  • The rate of achieving ≥VGPR was 74.4% vs 53.8% (P<0.0001) in frail patients, 85.2% vs 56.0% (P<0.0001) in total non-frail patients, 84.4% vs 57.4% (P<0.0001) in intermediate patients, and 86.8% vs 53.8% (P<0.0001) in fit patients receiving D-Rd vs Rd, respectively.
  • The rate of MRD-negativity was 23.8% vs 10.1% (P=0.0008) in frail patients, 33.2% vs 8.5% (P<0.0001) in total non-frail patients, 32.8% vs 9.0% (P<0.0001) in intermediate patients, and 33.8% vs 7.7% (P<0.0001) in fit patients receiving D-Rd vs Rd, respectively.
Safety
  • Incidence of serious TEAE was higher in the frail subgroup vs all other subgroups. The most common serious TEAE in patients receiving D-Rd vs Rd, respectively, was pneumonia across all subgroups: frail, 17.9% vs 8.4%; total non-frail, 10.7% vs 9.0%; intermediate, 10.2% vs 9.8%; and fit, 11.8% vs 7.8%.
  • The most common (≥10%) grade 3/4 TEAEs and TEAEs with an outcome of death (>1 patient, safety population) are summarized in Table: Summary of Safety Data.

Summary of Safety Data8
Parameter, n (%)
Non-frail
Frail (n=334)
Fit (n=145)
Intermediate (n=250)
Total Non-frail (n=395)
D-Rd (n=68)
Rd
(n=77)
D-Rd
(n=128)
Rd
(n=122)
D-Rd
(n=196)
Rd
(n=199)
D-Rd
(n=168)
Rd
(n=166)
Total number of patients with grade 3/4 TEAEs
58 (85.3)
61 (79.2)
117 (91.4)
104 (85.2)
175 (89.3)
165 (82.9)
159 (94.6)
148 (89.2)
Hematologic TEAEs
   Neutropenia
30 (44.1)
22 (28.6)
59 (46.1)
52 (42.6)
89 (45.4)
74 (37.2)
97 (57.7)
55 (33.1)
   Lymphopenia
7 (10.3)
7 (9.1)
18 (14.1)
14 (11.5)
25 (12.8)
21 (10.6)
31 (18.5)
18 (10.8)
   Leukopenia
7 (10.3)
2 (2.6)
11 (8.6)
10 (8.2)
18 (9.2)
12 (6.0)
22 (13.1)
9 (5.4)
   Anemia
4 (5.9)
11 (14.3)
17 (13.3)
24 (19.7)
21 (10.7)
35 (17.6)
28 (16.7)
40 (24.1)
   Thrombocytopenia
4 (5.9)
3 (3.9)
8 (6.3)
12 (9.8)
12 (6.1)
15 (7.5)
17 (10.1)
18 (10.8)
Nonhematologic TEAEs
   Infections
16 (23.5)
22 (28.6)
46 (35.9)
30 (24.6)
62 (31.6)
52 (26.1)
70 (41.7)
46 (27.7)
   Pneumonia
7 (10.3)
5 (6.5)
13 (10.2)
11 (9.0)
20 (10.2)
16 (8.0)
33 (19.6)
17 (10.2)
   Cataract
10 (14.7)
8 (10.4)
11 (8.6)
9 (7.4)
21 (10.7)
17 (8.5)
13 (7.7)
19 (11.4)
   Pulmonary
   embolism
8 (11.8)
5 (6.5)
6 (4.7)
9 (7.4)
14 (7.1)
14 (7.0)
7 (4.2)
5 (3.0)
   Hypokalemia
7 (10.3)
5 (6.5)
12 (9.4)
10 (8.2)
19 (9.7)
15 (7.5)
18 (10.7)
20 (12.0)
   Hyperglycemia
2 (2.9)
2 (2.6)
13 (10.2)
4 (3.3)
15 (7.7)
6 (3.0)
12 (7.1)
8 (4.8)
Total number of patients with TEAE with an outcome of death
1 (1.5)
3 (3.9)
6 (4.7)
4 (3.3)
7 (3.6)
7 (3.5)
20 (11.9)
20 (12.0)
Abbreviations: D-Rd, DARZALEX + lenalidomide + dexamethasone; Rd, lenalidomide + dexamethasone; TEAE, treatment-emergent adverse event.
  • The 2 most common reasons for treatment discontinuation across all subgroups were PD and AEs. Median time to treatment discontinuation was 13.4 vs 12.1 months in frail patients, 19.1 vs 12.0 months in total non-frail patients, 16.4 vs 10.4 months in intermediate patients, and 22.3 vs 17.3 months in fit patients receiving D-Rd vs Rd, respectively.
  • TEAEs that led to treatment discontinuation most frequently were fatigue and pulmonary embolism in the D-Rd and Rd arms, respectively. The rates of treatment discontinuation due to TEAEs were highest in the frail subgroup:
    • Frail patients: 10.1% and 19.3% receiving D-Rd and Rd, respectively
    • Total non-frail patients: 6.6% and 15.6% receiving D-Rd and Rd, respectively
    • Intermediate patients: 6.3% and 16.4% receiving D-Rd and Rd, respectively
    • Fit patients: 7.4% and 14.3% receiving D-Rd and Rd, respectively
  • The rates of death and TEAEs resulting in death were highest in the frail subgroup. Deaths were reported in:
    • Frail patients: 33.9% and 34.3% receiving D-Rd and Rd, respectively
    • Total non-frail patients: 13.3% and 23.1% receiving D-Rd and Rd, respectively
    • Intermediate patients: 16.4% and 27.9% receiving D-Rd and Rd, respectively
    • Fit patients: 7.4% and 15.6% receiving D-Rd and Rd, respectively
  • Deaths were reported due to TEAEs in frail (11.9% vs 12.0%), total non-frail (3.6% vs 3.5%), intermediate (4.7% vs 3.3%), and fit (1.5% vs 3.9%) patients receiving D-Rd vs Rd, respectively.

Pooled Analysis of Transplant-Ineligible, High-Risk Patients with NDMM from MAIA and ALCYONE Studies

Jakubowiak et al (2022)9 reported the results of a pooled analysis of patient-level data of transplant-ineligible patients with NDMM and high cytogenetic risk from the MAIA and ALCYONE studies.

Study Design/Methods

  • Patients with baseline high-risk cytogenetics [del(17p), t(4;14), or t(14;16)] were included.
  • Primary endpoint: PFS
  • Secondary endpoint: ORR, ≥CR, ≥VGPR, MRD-negative CR

Results

Patient Characteristics
  • Overall, 101 patients (D-Rd [MAIA], n=48; DARZALEX + bortezomib + melphalan + prednisone [D-VMP; ALCYONE], n=53) were included in the pooled DARZALEX cohort and 89 patients (Rd [MAIA], n=44; bortezomib + melphalan + prednisone [VMP; ALCYONE], n=45) were included in the pooled control cohort.
  • The combined median follow-up duration of both the trials was 43.7 months (MAIA, 47.9 months; ALCYONE, 40.1 months).
  • In the pooled DARZALEX and control cohorts, the median duration of treatment was 19.9 and 12.0 months, respectively.
  • Baseline characteristics of patients in the MAIA study are summarized in Table: Summary of Baseline Characteristics in MAIA.

Summary of Baseline Characteristics in MAIA9
Characteristic, n (%)
D-Rd (n=48)
Rd (n=44)
Standardized Differencea
Median age, years
74.5
74.0
-
   <75 years
24 (50.0)
24 (54.5)
9.1%
   ≥75 years
24 (50.0)
20 (45.5)
9.1%
Male
24 (50.0)
20 (45.5)
9.1%
ECOG PS score
   0
17 (35.4)
18 (40.9)
11.3%
   1
18 (37.5)
17 (38.6)
2.3%
   ≥2
13 (27.1)
9 (20.5)
15.6%
Type of MM by immunofixation or serum FLC
   IgG
35 (72.9)
28 (63.6)
20.0%
   Non-IgG
13 (27.1)
16 (36.4)
20.0%
ISS stageb
   I
6 (12.5)
8 (18.2)
15.8%
   II
21 (43.8)
15 (34.1)
19.9%
   III
21 (43.8)
21 (47.7)
8.0%
Cytogenetic riskc
   del(17p)
25 (52.1)
29 (65.9)
28.4%
   t(4;14)
21 (43.8)
12 (27.3)
35.0%
   t(14;16)
4 (8.3)
5 (11.4)
10.2%
Renal impairmentd
25 (52.1)
19 (43.2)
17.9%
Abbreviations: del, deletion; D-Rd, DARZALEX + lenalidomide + dexamethasone; ECOG PS, Eastern Cooperative Oncology Group performance status; FISH, fluorescence in situ hybridization; FLC, free light chain; IgG, immunoglobulin G; ISS, International Staging System; MM, multiple myeloma; Rd, lenalidomide + dexamethasone; t, translocation.
aStandardized difference is a measure of effect size independent of sample size, where characteristics with a standardized difference <10% were considered balanced.
bISS staging was derived based on the combination of serum β2-microglobulin and albumin.
cCytogenetic risk was based on FISH or karyotype testing.
dRenal impairment was defined as having baseline creatinine clearance <60 mL/minute.
Efficacy
  • The median PFS was 21.2 months in the pooled DARZALEX cohort vs 19.3 months in the pooled control cohort (adjusted HR, 0.59; 95% CI, 0.41-0.85; P=0.0046), representing a 41% reduction in risk of disease progression or death.
    • After adjusting for age differences, the pooled HR for PFS was 0.59 (95% CI, 0.41-0.85; P=0.0044).
    • In the subgroup of patients with del(17p) at baseline (pooled DARZALEX, n=54; pooled control, n=56) the adjusted HR for PFS was 0.63 (95% CI, 0.39-1.03; P=0.0659).
    • In the individual studies, the adjusted HRs for PFS were 0.73 (95% CI, 0.46-1.14) in the ALCYONE study and 0.57 (95% CI, 0.33-1.00) in the MAIA study. See Table: HRs for PFS in Individual Studies.
  • The 36-month PFS rate was 41.3% in the pooled DARZALEX cohort vs 19.9% in the pooled control cohort.

HRs for PFS in Individual Studies9
Study Name
Progression Events
Adjusted HR (95% CI)
DARZALEX + Control
n/N
Control
n/N
ALCYONE
41/53
36/45
0.73 (0.46-1.14)
MAIA
23/48
28/44
0.57 (0.33-1.00)
Pooleda
64/101
64/89
0.59 (0.41-0.85)
Abbreviations: CI, confidence interval; del, deletion; ECOG PS, Eastern Cooperative Oncology Group performance status; HR, hazard ratio; IgG, immunoglobulin G; ISS, International Staging System; PFS, progression-free survival; t, translocation.
aFor the pooled analysis, a multivariate stratified Cox regression analysis was used to calculate adjusted HR, with the study identifier as the stratification factor. HR was adjusted for cytogenetic abnormalities [ie, del(17p), t(4, 14), 4(14, 16)], baseline ECOG PS, ISS stage, type of multiple myeloma (ie, IgG vs. non-IgG), and renal impairment (defined as creatinine clearance <60 mL/min).
  • The median time to ≥CR was 9.3 months (range, 3.5-34.5) in the pooled DARZALEX cohort vs 7.1 months (range, 2.3-43.8) in the pooled control cohort. See Table: Response Rates.
  • In the pooled DARZALEX vs control cohorts, the median PFS was NR vs 31 months in patients achieving ≥CR and 16.4 months vs 15.6 months in patients not achieving CR.

Response Rates9
Parameter
DARZALEX + Control (n=101)
Control (n=89)
Relative Response Ratioa (95% CI)
Adjusted ORb
(95% CI)
P Value
Sensitivity Analysis Adjusting For Age
Adjusted ORc (95% CI)
P Value
Best response
   ≥CR (sCR + CR)
42 (41.6%)
20 (22.5%)
1.85
(1.18-2.90)
2.63
(1.34-5.16)
0.0051
2.57
(1.30-5.06)
0.0064
      sCR
27 (26.7%)
5 (5.6%)
-
-
-
-
-
      CR
15 (14.9%)
15 (16.9%)
-
-
-
-
-
      MRD-negative
      CR
25 (24.8%)
5 (5.6%)
4.35
(1.75-10.82)
5.50
(1.97-15.34)
0.0011
5.31
(1.89-14.88)
0.0015
   VGPR
34 (33.7%)
21 (23.6%)
-
-
-
-
-
   PR
17 (16.8%)
25 (28.1%)
-
-
-
-
-
   SD
3 (3.0%)
19 (21.3%)
-
-
-
-
-
   PD
0 (0.0%)
0 (0.0%)
-
-
-
-
-
   NE
5 (5.0%)
4 (4.5%)
-
-
-
-
-
≥VGPR (sCR + CR + VGPR)
76 (75.2%)
41 (46.1%)
1.64
(1.27-2.10)
4.03
(2.09-7.78)
<0.0001
4.08
(2.10-7.91)
<0.0001
Overall response (sCR + CR + VGPR + PR)
93 (92.1%)
66 (74.2%)
1.24
(1.08-1.42)
4.88
(1.94-12.27)
0.0008
4.71
(1.87-11.88)
0.0010
Abbreviations: CI, confidence interval; CR, complete response; del, deletion; ECOG PS, Eastern Cooperative Oncology Group performance status; IgG, immunoglobulin G; ISS, International Staging System; MM, multiple myeloma; MRD, minimal residual disease; NE, not evaluable; OR, odds ratio; PD, progressive disease; PR, partial response; sCR, stringent complete response; SD, stable disease; t, translocation; VGPR, very good partial response.
aRelative response ratio was calculated using the Mantel-Haenszel method, with the study identifier as the stratification factor.
bAdjusted OR was calculated using stratified logistic regression analysis, with the study identifier as the stratification factor. OR was adjusted for cytogenetic abnormalities [ie, del(17p), t(4;14), 4(14;16)], baseline ECOG PS, ISS stage, type of MM (ie, IgG vs non-IgG), and renal impairment (defined as creatinine clearance <60 mL/minute).
cOR was additionally adjusted for age (<75 vs ≥75 years).

Subgroup Analysis in Patients with Renal Impairment and/or High Cytogenetic Risk in the MAIA Study

Facon et al (2022)10 conducted a subgroup analysis of the phase 3 MAIA study that evaluated the efficacy and PROs of D-Rd vs Rd in subgroups of patients with NDMM who had renal impairment (CrCl ≤60 mL/min) and/or high-risk cytogenetics (del17p, t[4;14], or t[14;16] abnormality).

Study Design/Methods

  • Renal impairment was defined as CrCl ≤60 mL/min
  • Patients with high cytogenetic risk had a del17p, t(4;14), or t(14;16) abnormality.

Results

Patient Characteristics

Baseline Renal Function and Cytogenetic Risk Status10
Characteristic
D-Rd (n=368)
Rd (n=369)
Baseline renal function (CrCl), n (%)
   >60 mL/min
206 (56.0)
227 (61.5)
   ≤60 mL/min
162 (44.0)
142 (38.5)
Cytogenetic riska, n
319
323
   Standard risk, n (%)
271 (85.0)
279 (86.4)
   High risk, n (%)
48 (15.0)
44 (13.6)
Abbreviations: CrCl, creatinine clearance; del, deletion; D-Rd, DARZALEX + lenalidomide + dexamethasone; IMWG, International Myeloma Working Group; Rd, lenalidomide + dexamethasone; t, translocation.
aCytogenetic risk was evaluated based on local fluorescence in situ hybridization or karyotype testing. Patients with high cytogenetic risk had a del17p, t(4;14), or t(14;16) abnormality per IMWG 2016 recommendations. Patients with standard cytogenetic risk had an absence of high-risk cytogenetic abnormalities.
Efficacy

Efficacy Outcomes in the Overall Study Population and in Renal Function and Cytogenetic Risk Subgroups10
Parameter
D-Rd
Rd
HR (95% CI)
P Value
Median time to ≥VGPR, monthsa,b
   ITT population
3.8
9.4
2.08 (1.73-2.49)
<0.0001
   Renal function
      CrCl ≤60 mL/min
3.8
12.5
2.26 (1.69-3.02)
<0.0001
      CrCl >60 mL/min
3.8
8.5
1.82 (1.45-2.28)
<0.0001
   Cytogenetic risk status
      High risk
4.7
14.1
2.50 (1.44-4.36)
0.0008
      Standard risk
3.8
9.3
1.96 (1.59-2.40)
<0.0001
Median time to ≥CR, months
   Renal function
      CrCl ≤60 mL/min
23.3
54.6
1.58 (1.07-2.33)
0.0197
      CrCl >60 mL/min
17.6
43.8
1.80 (1.34-2.41)
<0.0001
   Cytogenetic risk status
      High risk
15.7
47.9
1.74 (0.83-3.63)
0.1372
      Standard risk
20.8
42.6
1.69 (1.29-2.21)
<0.0001
48-month EFS rate in patients achieving ≥CR, %
   ITT populationc,d
81.8
57.8
0.38 (0.23-0.65)
0.0002
   Renal function
      CrCl ≤60 mL/min
81.0
61.5
0.45 (0.20-1.04)
0.0551
      CrCl >60 mL/min
82.2
55.3
0.41 (0.22-0.77)
0.0043
   Cytogenetic risk status
      High risk
74.7
NE
0.32 (0.09-1.16)
0.0694
      Standard risk
80.0
55.1
0.42 (0.24-0.73)
0.0015
48-month EFS rate in patients achieving ≥PR, %
   Renal function
      CrCl ≤60 mL/min
67.2
44.4
0.50 (0.34-0.74)
0.0003
      CrCl >60 mL/min
69.8
48.9
0.50 (0.36-0.70)
<0.0001
      Cytogenetic risk status
      High risk
48.8
29.9
0.65 (0.35-1.19)
0.1560
      Standard risk
72.3
45.7
0.43 (0.32-0.57)
<0.0001
Abbreviations: CI, confidence interval; CR, complete response; CrCl, creatinine clearance; D-Rd, DARZALEX + lenalidomide + dexamethasone; EFS, event-free survival; HR, hazard ratio; ISS, International Staging System; ITT, intent-to-treat; NE, not evaluable; PR, partial response; Rd, lenalidomide + dexamethasone; VGPR, very good partial response.
aHR and 95% CI are calculated from a Cox proportional hazards model, with treatment as the sole explanatory variable. HR >1 indicates an advantage for D-Rd.
bP value was based on the log-rank test.
cHR and 95% CI are calculated from a Cox proportional hazards model, with treatment as the sole explanatory variable and stratified by ISS stage (I, II, or III), region (North America vs other), and age (<75 years vs ≥75 years), as randomized. HR <1 indicates an advantage for D-Rd.
dP value was based on a stratified log-rank test.
  • Among patients with renal impairment, greater improvements from baseline in patient-reported pain scores, patient-reported fatigue, and nausea and vomiting symptom scores were observed in the D-Rd vs Rd arm across most time points.
    • A greater meaningful reduction in pain score was reported in the D-Rd vs Rd arm, respectively, at cycle 6 day 1 (LS mean change from baseline, -14.9 vs -7.0; P=0.0241) in patients with renal impairment.
    • A greater reduction in fatigue symptom score was reported in the D-Rd vs Rd arm, respectively, at cycle 24 day 1 (LS mean change from baseline, -2.9 vs 8.1; P=0.0018), cycle 30 day 1 (LS mean change from baseline, -3.7 vs 4.4; P=0.0258), and cycle 36 day 1 (LS mean change from baseline, -2.6 vs 6.5; P=0.0183) in patients with renal impairment.
    • A greater reduction in nausea and vomiting symptom score was observed in the D-Rd vs Rd arm, respectively, at cycle 36 day 1 (LS mean change from baseline, -3.7 vs 3.3; P=0.0035) in patients with renal impairment.
  • Greater improvements from baseline in patient-reported symptoms were observed in the D-Rd vs Rd arm in patients without renal impairment (CrCl >60 mL/min).
  • Greater improvements from baseline in patient-reported pain score were observed in the D-Rd vs Rd arm across most time points in patients with standard and high cytogenetic risk.

Predictive and Prognostic Role of MRD-Negativity and Durability

San-Miguel et al (2022)11 evaluated the predictive and prognostic role of MRD-negativity and durability in patients with NDMM ineligible for transplant.

Results

Patient Characteristics

Demographics and Baseline Characteristics by MRD Durability24
Characteristic
D-Rd
Rd
ITT
(n=368)
MRD-Negative Patients
ITT
(n=369)
MRD-Negative Patients
At Any Time
(n=106)
≥12 Months
(n=40)
Not ≥12 Months
(n=66)
At Any Time
(n=34)
≥12 Months
(n=9)
Not ≥12 Months
(n=25)
Age, years
   Median (range)
73.0 (50-90)
72.0 (65-87)
71.0 (66-85)
73.5 (65-87)
74.0 (45-89)
72.5 (66-87)
71.0 (69-78)
73.0 (66-87)
   Distribution
   <75
208 (56.5)
68 (64.2)
31 (77.5)
37 (56.1)
208 (56.4)
20 (58.8)
6 (66.7)
14 (56.0)
   ≥75
160 (43.5)
38 (35.8)
9 (22.5)
29 (43.9)
161 (43.6)
14 (41.2)
3 (33.3)
11 (44.0)
ISS disease stagea
   I
98 (26.6)
24 (22.6)
10 (25.0)
14 (21.2)
103 (27.9)
11 (32.4)
5 (55.6)
6 (24.0)
   II
163 (44.3)
55 (51.9)
19 (47.5)
36 (54.5)
156 (42.3)
15 (44.1)
3 (33.3)
12 (48.0)
   III
107 (29.1)
27 (25.5)
11 (27.5)
16 (24.2)
110 (29.8)
8 (23.5)
1 (11.1)
7 (28.0)
Cytogenetic profileb
   Patients evaluated
319
96
34
62
323
27
8
19
   Standard-risk cytogenetic abnormality
271 (85.0)
85 (88.5)
29 (85.3)
56 (90.3)
279 (86.4)
26 (96.3)
8 (100.0)
18 (94.7)
   High-risk cytogenetic abnormalityc
48 (15.0)
11 (11.5)
5 (14.7)
6 (9.7)
44 (13.6)
1 (3.7)
0
1 (5.3)
      del(17p)
25 (7.8)
6 (6.3)
2 (5.9)
4 (6.5)
29 (9.0)
0
0
0
Abbreviations: del, deletion; D-Rd, DARZALEX + lenalidomide + dexamethasone; ISS, International Staging System; ITT, intention-to-treat; MRD, minimal residual disease; Rd, lenalidomide + dexamethasone; t, translocation.
All data are n (%) unless otherwise indicated.
aISS staging is derived based on the combination of serum β2-microglobulin and albumin.
bCytogenetic risk status was determined by fluorescence in situ hybridization or karyotype testing.
cHigh risk is defined as having a positive test for any of the del17p, t(14;16), or t(4;14) molecular abnormalities.
Efficacy
  • In the ITT population and among patients with ≥CR, patients receiving the D-Rd regimen achieved higher rates of MRD-negativity and durability compared with Rd. See Table: Rates of Sustained MRD-negativity Status in Transplant-ineligible NDMM.
  • In the ITT population, MRD-negative patients had improved PFS compared with MRD-positive patients (HR, 0.15; 95% CI, 0.09-0.26; P<0.0001).
  • Durable MRD-negativity lasting ≥6 months or ≥12 months improved PFS compared with MRD-negative patients who did not maintain MRD-negativity for ≥6 months or
    ≥12 months.
  • Estimated 36-month rates of time to subsequent anticancer therapy were mostly higher for patients who achieved MRD-negativity at any time vs MRD-positive patients, and for patients with sustained MRD-negativity lasting ≥6 months or ≥12 months compared with those who did not have durable MRD-negativity are presented in the Table: Estimated Rates of Patients Without Subsequent Therapy at 36 Months in ITT Population.
  • Estimated 36-month PFS2 rate (ITT; D-Rd, n=368; Rd, n=369):
    • MRD-negative (10-5) at ≥1 time point: D-Rd, 95.0% (n=106); Rd, 83.9% (n=34)
    • MRD-positive: D-Rd, 65.5% (n=262); Rd, 61.5% (n=335)

Rates of Sustained MRD-negativity Status in Transplant-ineligible NDMM11
MRD-Negativity (10-5)
(N=737)
D-Rd
Rd
P Valuea
ITT
n=368
n=369
   MRD-negative status, n (%)
106 (28.8)
34 (9.2)
<0.0001
      ≥6 months sustained
55 (14.9)
16 (4.3)
<0.0001
      ≥12 months sustained
40 (10.9)
9 (2.4)
<0.0001
≥CR
n=182
n=100
   MRD-negative status, n (%)
106 (58.2)
34 (34.0)
0.0001
      ≥6 months sustained
55 (30.2)
16 (16.0)
0.0097
      ≥12 months sustained
40 (22.0)
9 (9.0)
0.0053
Abbreviations: CR, complete response; D-Rd, DARZALEX + lenalidomide + dexamethasone; ITT, intention-to-treat; MRD, minimal residual disease; NDMM, newly diagnosed multiple myeloma; Rd, lenalidomide + dexamethasone.
aP value was calculated using Fisher’s exact test.

Estimated Rates of Patients Without Subsequent Therapy at 36 months in ITT Population11
Estimated 36-Month Time to Subsequent Anticancer Therapy Rate, n (%)
D-Rd (n=368)
Rd (n=369)
MRD-negative (10-5) at ≥1 time point
106 (96.9)
34 (90.5)
MRD-positive
262 (65.4)
335 (48.7)
Achieved and remained MRD-negative (10-5) for ≥6 months
55 (96.1)
16 (100.0)
MRD-negativity not ≥6 months
51 (98.0)
18 (78.7)
Achieved and remained MRD-negative (10-5) for ≥12 months
40 (94.6)
9 (100.0)
MRD-negativity not ≥12 months
66 (98.5)
25 (85.2)
Abbreviations: D-Rd, DARZALEX + lenalidomide + dexamethasone; ITT, intention-to-treat; MRD, minimal residual disease; Rd, lenalidomide + dexamethasone.

HRQoL Outcomes from the MAIA study

Perrot et al (2025)12 reported the final analysis results of a PRO analysis from the MAIA study, with a median follow-up of 64.5 months. Results from this updated analysis are summarized below.

Study Design/Methods

  • Patients were categorized as frail based on baseline age, ECOG PS, and the Charlson comorbidity index.
  • PROs were focused on the GHS, physical functioning, and pain and fatigue subscales of EORTC QLQ-C30.
  • The scores were transformed to a scale of 0 to 100.
  • The questionnaire was completed at baseline; on day 1 of cycles 3, 6, 9, and 12; and then every 6 cycles thereafter until PD.

Results

Patient Characteristics
  • Baseline patient characteristics of the ITT population were balanced across D-Rd and Rd treatment groups and are presented in Table: Baseline Patient Characteristics - ITT in MAIA Study.
  • In the ITT population and in subgroups, baseline PRO scores were similar between treatment groups.
  • Compliance with PRO assessments was >80% through cycle 42 but later decreased to ≥59% through cycle 66.
  • Scores of the EORTC QLQ-C30 subscales at cycle 36 are presented in Table: EORTC QLQ-C30 Subscales at Cycle 36.
  • A higher percentage of patients treated with D-Rd than that of patients treated with Rd showed significant improvements by cycle 36 (around year 3) in the GHS (OR, 1.84; 95% CI, 1.16-2.91), physical functioning (OR, 1.93; 95% CI, 1.18-3.14), pain (OR, 1.41; 95% CI, 0.90-2.22), and fatigue (OR, 2.00; 95% CI, 1.24-3.23) subscales. Additionally, more patients with bone lesions experienced improvements in GHS and physical functioning subscales with D-Rd vs Rd.
  • A larger proportion of patients treated with D-Rd experienced significant improvements compared to those treated with Rd by cycle 60 in the GHS (OR, 1.11; 95% CI, 0.56-2.20), physical functioning (OR, 2.67; 95% CI, 1.23-5.77), pain (OR, 1.97; 95% CI, 0.91-4.25), and fatigue (OR, 1.73; 95% CI, 0.85-3.55) subscales.

Baseline Patient Characteristics - ITT in MAIA Study12
Characteristic
D-Rd
(n=368)
Rd
(n=369)
Age, years, %
   <70
21
21
   ≥70 to <75
35
36
   ≥75
43
44
Frail, %
47
46
Bone lesions, %
70.1
70.7
Abbreviations: D-Rd, DARZALEX + lenalidomide + dexamethasone; PRO, patient-reported outcome; Rd, lenalidomide + dexamethasone.

EORTC QLQ-C30 Subscales at Cycle 3612
Subscale
D-Rd, n
Rd, n
OR (95% CI)
EORTC QLQ-C30 GHS
   ITT
207
119
1.84 (1.16-2.91)
   Frail
84
44
1.75 (0.84-3.66)
   Age
      <70 years
55
26
1.19 (0.47-3.05)
      ≥70 to <75
73
46
3.85 (1.74-8.53)
      ≥75 years
79
47
1.19 (0.57-2.46)
   Bone lesions
158
89
1.71 (1.01-2.88)
EORTC QLQ-C30 pain
   ITT
207
119
1.41 (0.90-2.22)
   Frail
84
44
1.68 (0.81-3.50)
   Age
      <70 years
55
26
1.39 (0.54-3.57)
      ≥70 to <75
73
46
2.11 (0.99-4.47)
      ≥75 years
79
47
0.94 (0.45-1.94)
   Bone lesions
158
89
1.42 (0.84-2.39)
EORTC QLQ-C30 physical functioning
   ITT
207
119
1.93 (1.18-3.14)
   Frail
84
44
1.44 (0.69-3.03)
   Age
      <70 years
55
26
1.95 (0.70-5.40)
      ≥70 to <75
73
46
3.79 (1.60-8.96)
      ≥75 years
79
47
1.08 (0.51-2.28)
   Bone lesions
158
89
2.31 (1.32-4.04)
EORTC QLQ-C30 fatigue
   ITT
207
119
2.00 (1.24-3.23)
   Frail
84
44
1.09 (0.52-2.27)
   Age
      <70 years
55
26
2.27 (0.86-5.96)
      ≥70 to <75
73
46
2.77 (1.22-6.29)
      ≥75 years
79
47
1.31 (0.61-2.80)
Abbreviations: CI, confidence interval; D-Rd, DARZALEX + lenalidomide + dexamethasone; EORTC QLQ-C30, European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire Core 30; GHS, global health status; ITT, intent-to-treat; OR, odds ratio; Rd, lenalidomide + dexamethasone.

Literature Search

A literature search of MEDLINE®, Embase®, BIOSIS Previews®, and Derwent Drug File (and/or other resources, including internal/external databases) was conducted on 04 April 2025.

 

References

Show
1 Facon T, Kumar S, Plesner T, et al. Daratumumab plus lenalidomide and dexamethasone for untreated myeloma. N Engl J Med. 2019;380:2104-2115.  
2 Facon T, Kumar SK, Plesner T, et al. Phase 3 randomized study of daratumumab plus lenalidomide and dexamethasone (D-Rd) versus lenalidomide and dexamethasone (Rd) in patients with newly diagnosed multiple myeloma (NDMM) ineligible for transplant (MAIA). Oral presentation presented at: 60th American Society of Hematology (ASH) Annual Meeting & Exposition; December 1-4, 2018; San Diego, CA.  
3 Facon T, Moreau P, Weisel K, et al. Daratumumab/lenalidomide/dexamethasone in transplant-ineligible newly diagnosed myeloma: MAIA long-term outcomes. [published online ahead of print February 27, 2025]. 2025. doi:10.1038/s41375-024-02505-2.  
4 Facon T, Moreau P, Weisel K, et al. Supplement to: Daratumumab/lenalidomide/dexamethasone in transplant-ineligible newly diagnosed myeloma: MAIA long-term outcomes. [published online ahead of print February 27, 2025]. 2025. doi:10.1038/s41375-024-02505-2.  
5 Facon T, Kumar SK, Orlowski R, et al. Final survival analysis of daratumumab plus lenalidomide and dexamethasone versus lenalidomide and dexamethasone in transplant-ineligible patients with newly diagnosed multiple myeloma: MAIA study. Poster presented at: The European Hematology Association (EHA) Hybrid Congress; June 13-16, 2024; Madrid, Spain.  
6 Moreau P, Facon T, Usmani SZ, et al. Daratumumab plus lenalidomide/dexamethasone in untreated multiple myeloma: analysis of key subgroups of the MAIA study. Leukemia. 2025;39(3):710-719.  
7 Moreau P, Facon T, Usmani S, et al. Treatment duration and long-term outcomes with daratumumab in transplant-ineligible newly diagnosed multiple myeloma from the phase 3 MAIA study. Oral presentation2022.  
8 Facon T, Cook G, Usmani SZ, et al. Daratumumab plus lenalidomide and dexamethasone in transplant-ineligible newly diagnosed multiple myeloma: frailty subgroup analysis of MAIA. Leukemia. 2022;36(4):1066-1077.  
9 Jakubowiak AJ, Kumar S, Medhekar R, et al. Daratumumab Improves Depth of Response and Progression-free Survival in Transplant-ineligible, High-risk, Newly Diagnosed Multiple Myeloma. Oncol. 2022;27(7):oyac067-.  
10 Facon T, Kumar S, Plesner T, et al. Time to response, duration of response, and patient-reported outcomes (PROs) with daratumumab (DARA) plus lenalidomide and dexamethasone (D-Rd) versus lenalidomide and dexamethasone (Rd) alone in transplant-ineligible patients with newly diagnosed multiple myeloma (NDMM): subgroup analysis of the phase 3 MAIA study. Poster presented at: American Society of Clinical Oncology (ASCO) Annual Meeting; June 3-7, 2022; Chicago, IL/Virtual Meeting.  
11 San-Miguel J, Avet-Loiseau H, Paiva B, et al. Sustained minimal residual disease negativity with daratumumab in newly diagnosed multiple myeloma: MAIA and ALCYONE. Blood. 2022;139:492-501.  
12 Perrot A, Facon T, Plesner T, et al. Sustained improvement in health‐related quality of life in transplant‐ineligible newly diagnosed multiple myeloma treated with daratumumab, lenalidomide, and dexamethasone: MAIA final analysis of patient‐reported outcomes. Eur J Haematol. 2025;0:1-7.  
13 Cavo M, San-Miguel J, Usmani SZ, et al. Prognostic value of minimal residual disease negativity in myeloma: combined analysis of POLLUX, CASTOR, ALCYONE, and MAIA. Blood. 2021;139(6):835-844.  
14 Cavo M, San-Miguel J, USmani S, et al. Supplement to: Prognostic value of minimal residual disease negativity in myeloma: combined analysis of POLLUX, CASTOR, ALCYONE, MAIA. Blood. 2022;139:835-844.  
15 Wang J, Arroyo-Suarez R, Dasari S, et al. Early versus late response to daratumumab-based triplet therapies in patients with multiple myeloma: a pooled analysis of trials POLLUX, CASTOR and MAIA. Leuk Lymphoma. 2022;63(7):1669-1677.  
16 Perrot A, Facon T, Plesner T, et al. Health related quality of life for frail transplant ineligible patients with newly diagnosed multiple myeloma treated with daratumumab, lenalidomide, and dexamethasone: subgroup analysis of MAIA trial. 2022;(Oral presentation).  
17 Perrot A, Facon T, Kumar S, et al. Sustained improvement in health-related quality of life in transplant-ineligible patients with newly diagnosed multiple myeloma treated with daratumumab, lenalidomide and dexamethasone versus lenalidomide and dexamethasone: update of the phase 3 MAIA trial. Poster presented at: 63rd American Society of Hematology (ASH) Annual Meeting & Exposition; December 11-14, 2021; Atlanta, GA/Virtual.  
18 Perrot A, Facon T, Kumar S, et al. Meaningful changes in patient-reported outcomes in relation to best clinical response and disease progression: post hoc analyses from MAIA. Poster presented at: 63rd American Society of Hematology (ASH) Annual Meeting & Exposition; December 11-14, 2021; Atlanta, GA/Virtual.  
19 Nahi H, Usmani SZ, Mateos MV, et al. Efficacy of daratumumab, lenalidomide, and dexamethasone in transplant-ineligible patients with newly diagnosed multiple myeloma and impaired renal function from the phase 3 MAIA study based on lenalidomide starting dose. Poster presented at: 63rd American Society of Hematology (ASH) Annual Meeting & Exposition; December 11-14, 2021; Atlanta, GA/Virtual Meeting.  
20 Moreau P, Facon T, Usmani S, et al. Effect of lenalidomide (R) ¬± dexamethasone (d) discontinuation on daratumumab efficacy in multiple myeloma (MM): subgroup analysis of the phase 3 MAIA and POLLUX studies. presented at: 8th Annual Meeting of the Society of Hematologic Oncology (SOHO); September 9-12, 2020; Virtual.  
21 Bahlis N, Facon T, S. Usmani, et al. Daratumumab plus lenalidomide and dexamethasone (D-Rd) versus lenalidomide and dexamethasone (Rd) in patients with newly diagnosed multiple myeloma (NDMM) ineligible for transplant: updated analysis of MAIA. Poster presented at: 61st American Society of Hematology (ASH) Annual Meeting & Exposition; December 7-10, 2019; Orlando, FL.  
22 Kumar S, Facon T, Usmani S, et al. Updated analysis of daratumumab plus lenalidomide and dexamethasone (D-Rd) versus lenalidomide and dexamethasone (Rd) in patients with transplant-ineligible newly diagnosed multiple myeloma (NDMM): the phase 3 MAIA study. Virtual 62nd American Society of Hematology (ASH) Annual Meeting & Exposition. 2020.  
23 Facon T, Kumar S, Plesner T, et al. Supplement to: Daratumumab, lenalidomide, and dexamethasone versus lenalidomide and dexamethasone alone in newly diagnosed multiple myeloma (MAIA): overall survival results from a randomised, open-label, phase 3 trial. Lancet Oncol. 2021;22(11):1582-1596.  
24 San-Miguel J, Avet-Loiseau H, Paiva B, et al. Supplement to: Sustained minimal residual disease negativity with daratumumab in newly diagnosed multiple myeloma: MAIA and ALCYONE. Blood. 2022;139:492-501.