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DARZALEX® (daratumumab)
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DARZALEX - MAIA Study

Last Updated: 06/04/2026

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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, and Final Survival Analysis.
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 was 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 (TIE) 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). The most common (>10%) grade 3/4 adverse events (AEs) were neutropenia, anemia, leukopenia, lymphopenia, and infections.
    • 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. 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). 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.  
    • 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, 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]). Deaths were reported for 47.5% of patients in the D-Rd arm and 59.7% of patients in the Rd arm, mostly due to disease progression.
  • Venner et al (2026)6 presented the results of an age and frailty analysis of TIE patients in the MAIA and CEPHEUS studies. Overall and sustained minimal residual disease (MRD; 10-5) in patients with complete response or better (≥CR) were improved with D-Rd vs Rd across both age and frailty subgroups. Rates of grade 3/4 TEAEs were generally higher in frail vs nonfrail and older vs younger patients within treatment arms.
  • Mian et al (2025)7 presented the results of a post hoc analysis assessing outcomes based on dynamic frailty of TIE patients in the CEPHEUS and MAIA studies. Frailty in patients with TIE NDMM changed in 26% of MAIA patients with data over 4 years. Deterioration of frailty level was due to increases in both Eastern Cooperative Oncology Group performance status (ECOG PS) and age. D-Rd vs Rd resulted in a 34-50% decrease in the risk of progression/death in non-frail patients and a 46-58% decrease in frail patients. In ultrafrail patients, D-Rd reduced the risk by 56-72%. Incidence of related serious TEAEs and TEAEs leading to treatment discontinuation was generally similar or lower in patients receiving D-VRd vs VRd, regardless of changes in frailty. 
  • Moreau et al (2022)8 presented the results of a post hoc analysis of the 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.
  • Other relevant literature has been identified in addition to the data summarized above.9-15

CLINICAL DATA

Phase 3 Study of DARZALEX in Combination with Rd in TIE NDMM

MAIA (MMY3008; NCT02252172) was a phase 3, randomized, open-label, active-controlled, multicenter, international study in patients with NDMM not eligible for high-dose chemotherapy and autologous stem cell transplantation (ASCT; N=737).1,2.

Study Design/Methods

  • 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, ECOG PS 0-2, creatinine clearance (CrCl) ≥30 mL/min.1,2
  • Patients were randomized 1:1 to D-Rd (n=368) or Rd (n=369) and received 28-day cycles of the following treatment.1,2
    • 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 intravenous (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.
  • Patients in the D-Rd arm were administered the following pre-infusion medications16:
    • Acetaminophen 650-1000 mg IV/PO
    • Diphenhydramine 25-50 mg (or equivalent) IV/PO
    • Dexamethasone 40 mg IV/PO approximately 1 hour prior to DARZALEX infusion
      (20 mg once weekly for patients >75 years of age or with a BMI <18.5 kg/m2)
  • 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 (FEV1) <80% could receive the following post-infusion mediations: diphenhydramine (or equivalent), short-acting ß2 adrenergic receptor agonists, control medications for lung disease.16
  • 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).16
  • 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).1,2
  • Primary endpoint: PFS.1,2
  • 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.1,2

Primary Analysis of the MAIA Study

Facon et al (2019)1 reported the prespecified interim results of the MAIA study at a median follow-up of 28.0 months (range, 0.0-41.4).

Results

Efficacy
  • 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.1
  • HR for the primary endpoint of PFS was 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.1
  • Median time to first response was 1.05 months in both arms.1
  • Median PFS: 31.9 months for Rd (95% CI, 28.9-NR); NR for D-Rd.1
    • 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).1
  • ≥CR was achieved in 175 patients (47.6%) in the D-Rd arm vs 92 patients (24.9%) in the Rd arm (P<0.001).1
  • Median time to ≥CR was 10.4 months for D-Rd and 11.2 months for Rd.1
  • ≥VGPR rate of 79.3% was reported for D-Rd vs 53.1% for Rd (P<0.001).1
  • MRD-negativity was >3 times higher with D-Rd than with Rd (89 [24.2%] vs 27 [7.3%]; P<0.001).1
  • HR for OS: 0.78 (95% CI, 0.56-1.1); data immature after a median follow-up of 28.0 months.1
Safety

Most Common Adverse Events in the Safety Populationa, 1
Most Common (>30%) Any Grade AEs
Most Common (>10%) Grade 3/4 AEs
Hematologic
  • Neutropenia
  • Anemia

Nonhematologic
  • Infections
  • Diarrhea
  • Constipation
  • Fatigue
  • Peripheral edema
  • Back pain
  • Asthenia
  • Nausea
  • Any IRR
Hematologic
  • Neutropenia
  • Anemia
  • Leukopenia
  • Lymphopenia

Nonhematologic
  • Infections (including pneumonia)
Abbreviations: AE, adverse event; IRR, infusion-related reaction.
aThe safety population included all patients who received at least 1 dose of the trial treatment. AEs of any grade that were reported in >30% of patients in either treatment arm and grade 3/4 AEs that were reported in >10% of patients in either treatment arm are listed.
  • Serious AEs: 62.9% for D-Rd; 62.7% for Rd1
  • AEs leading to discontinuation: 7.1% for D-Rd; 15.9% for Rd1
  • TEAEs with outcome of death: 6.9% for D-Rd; 6.3% for Rd1
    • Pneumonia was the most common AE that resulted in death (D-Rd, 0.5%; Rd, 0.8%).
  • Second primary cancers: 8.8% for D-Rd; 7.1% for Rd1

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 (range, 0-77.6).

Results

Patient Characteristics

Demographic and Baseline Disease Characteristics of the ITT Population4
Characteristic
D-Rd
(n=368)
Rd
(n=369)
Median age (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).
  • The median treatment duration was 47.5 months (range, 0.1-77.3) vs 22.6 months (range, 0.03-77.5) in the D-Rd vs Rd arm, respectively. 
  • As of the clinical cutoff date of October 21, 2021, 233 (64.0%) vs 311 (85.2%) patients from the D-Rd vs Rd arm, respectively, discontinued treatment; the main reasons for discontinuation were PD (D-Rd, 29.4%; Rd, 35.9%) and AEs (D-Rd, 15.7%; Rd, 24.4%).
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 estimated 60-month PFS rate was 52.1% vs 29.6% in the D-Rd vs Rd arm, respectively.
  • The PFS benefit with D-Rd vs Rd was consistent across prespecified subgroups based on baseline characteristics as presented in Table: Analysis of PFS in Pre-specified Patient Subgroups.

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).
  • 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 estimated 60-month OS rate was 66.6% vs 53.6% in the D-Rd vs Rd arm, respectively.
  • The OS benefit with D-Rd vs Rd was consistent across prespecified patient subgroups based on baseline characteristics as presented in Table: Analysis of OS in Pre-specified Patient Subgroups.

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).
  • The D-Rd vs Rd arm showed a significantly higher MRD-negativity rate (10-5 sensitivity) and sustained MRD-negativity rate (10-5 sensitivity) 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.
    • 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.
  • 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.3
    • 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.

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.
  • For patients who achieved ≥CR3:
    • 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 VGPR3:
    • 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.
  • A total of 128 patients (35.2%) vs 194 patients (53.2%) 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).
Safety
  • At clinical cutoff, 52 patients from the D-Rd arm discontinued lenalidomide ± dexamethasone but remained on the rest of the study treatment; 46 of these patients (88.5%) 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.

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.
    • 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.

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 89.3 months (range, 0-102.2).

Results

Efficacy
  • At the median follow-up, the 7-year OS rate was 53.1% for the D-Rd arm and 39.3% for the Rd arm.5
  • 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.5

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).
  • 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.

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
  • Among the safety population, 78.3% of patients (n=285) 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 (38.6%) arms.
    • A lower proportion of patients in the D-Rd (16.5%) and Rd (25.8%) arms 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.

Age and Frailty Analysis of TIE Patients in the MAIA Study

Venner et al (2026)6 presented the results of an age and frailty analysis of TIE patients in the MAIA and CEPHEUS studies. Results specific to the MAIA study are summarized below.

Study Design/Methods

  • A subgroup analysis of patients from the MAIA study at a median follow-up of 64.5 months was conducted.6
  • Subgroups included age (<70, 70-<75, or ≥75 years) and frailty status based on the IFM simplified frailty score at baseline (nonfrail [score=0/1] or frail [score≥2]).6

Results

Patient Characteristics
  • A total of 737 patients were included from the MAIA study (D-Rd, n=368; VRd, n=369).6
  • The median age was 73 years (range, 45-90).6
  • There were 155 patients (21%) who were <70 years, 261 patients (35%) were 70-<75 years, and 321 patients (44%) were ≥75 years.6
  • A total of 341 patients (46%) were frail, of which 88% were 70 years or older.6
Efficacy

MRD Negativity (≥CR; 10-5) Rates Across Age and Frailty Subgroups6
Subgroup
Overall MRD negativity rate, n (%)
Sustained MRD negativity rate ≥12 months, n (%)
D-Rd
Rd
OR (95% CI)
D-Rd
Rd
OR (95% CI)
Age
   <70 years
35.9
11.7
4.23 (1.84-9.75)
25.6
3.9
8.51 (2.41-30.02)
   70-<75 years
36.2
12.2
4.07 (2.16-7.67)
20.8
5.3
4.64 (1.94-11.10)
   ≥75 years
26.9
9.9
3.33 (1.79-6.21)
13.8
3.1
4.97 (1.83-13.49)
Frailty
   Nonfrail
37.8
9.5
5.78 (3.32-10.05)
21.4
4.0
6.55 (2.98-14.35)
   Frail
25.6
13.0
2.30 (1.31-4.04)
15.7
4.1
4.31 (1.82-10.19)
Abbreviations: CI, confidence interval; CR, complete response; D-Rd, DARZLEX + lenalidomide + dexamethasone; MRD, minimal residual disease; OR, odds ratio; Rd, lenalidomide + dexamethasone.

PFS Across Age and Frailty Subgroups6
Subgroup
Median PFS, months
HR (95% CI)
D-Rd
Rd
Age
   <70 years
NE
39.16
0.35 (0.21-0.56)
   70-<75 years
61.93
37.52
0.64 (0.45-0.89)
   ≥75 years
54.31
31.38
0.59 (0.44-0.79)
Frailty
   Nonfrail
73.72
37.78
0.48 (0.36-0.64)
   Frail
52.17
30.39
0.64 (0.48-0.85)
Abbreviations: CI, confidence interval; D-Rd, DARZLEX + lenalidomide + dexamethasone; HR, hazard ratio; NE, not estimable; PFS, progression-free survival; Rd, lenalidomide + dexamethasone.
Safety

Safety Summary Across Age Subgroups6
Event, n (%)
<70 years
70-<75 years
≥75 years
D-Rd
(n=78)
Rd
(n=76)
D-Rd
(n=129)
Rd
(n=130)
D-Rd
(n=157)
Rd
(n=159)
Any grade 3/4 TEAE
72 (92.3)
62 (81.6)
127 (98.4)
111 (85.4)
150 (95.5)
151 (95.0)
Neutropenia
37 (47.4)
21 (27.6)
62 (48.1)
48 (36.9)
98 (62.4)
66 (41.5)
Infections and infestations SOCa
29 (37.2)
19 (25.0)
58 (45.0)
36 (27.7)
68 (43.3)
53 (33.3)
TEAE leading to treatment discontinuation
9 (11.5)
11 (14.5)
20 (15.5)
32 (24.6)
24 (15.3)
44 (27.7)
≥1 related serious TEAE, %
42.3
38.2
51.2
36.9
52.2
52.8
Death due to TEAE
7 (9.0)
3 (3.9)
6 (4.7)
10 (7.7)
16 (10.2)
18 (11.3)
Death due to PD
7 (9.0)
12 (15.8)
22 (17.1)
27 (20.8)
27 (17.2)
30 (18.9)
Abbreviations: D-Rd, DARZLEX + lenalidomide + dexamethasone; PD, progressive disease; Rd, lenalidomide + dexamethasone; SOC, system organ class; TEAE, treatment-emergent adverse event.
aCOVID-19 infections/pneumonia were reported in <2% of patients in the D-Rd arm across subgroups.

Safety Summary Across Frailty Subgroups6
Event, n (%)
Nonfrail
Frail
D-Rd
(n=196)
Rd
(n=199)
D-Rd
(n=168)
Rd
(n=166)
Any grade 3/4 TEAE
188 (95.9)
172 (86.4)
161 (95.8)
152 (91.6)
Neutropenia
96 (49.0)
79 (39.7)
101 (60.1)
56 (33.7)
Infections and infestations SOCa
77 (39.3)
55 (27.6)
78 (46.4)
53 (31.9)
TEAE leading to treatment discontinuation
26 (13.3)
47 (23.6)
27 (16.1)
40 (24.1)
≥1 related serious TEAE, %
45.5
41.7
54.8
47.0
Death due to TEAE
7 (3.6)
10 (5.0)
22 (13.1)
21 (12.7)
Death due to PD
26 (13.3)
40 (20.1)
30 (17.9)
29 (17.5)
Abbreviations: D-Rd, DARZLEX + lenalidomide + dexamethasone; PD, progressive disease; Rd, lenalidomide + dexamethasone; SOC, system organ class; TEAE, treatment-emergent adverse event.
aCOVID-19 infections/pneumonia were reported in <2% of patients in the D-Rd arm across subgroups.

Post Hoc Analysis of Outcomes Based on Dynamic Frailty in MAIA Patients

Mian et al (2025)7 presented the results of a post hoc analysis assessing outcomes based on dynamic frailty of transplant ineligible patients in the CEPHEUS and MAIA studies. Results specific to the MAIA study are summarized below.

Study Design/Methods

  • Patients were randomized 1:1 to receive D-VRd vs VRd (CEPHEUS; TIE patients only) or D-Rd vs Rd (MAIA).7
  • Frailty was assessed using IFM simplified frailty score (nonfrail, score 0/1; frail score ≥2; ultrafrail score ≥3) at baseline and 12, 24, 36, and 48 months.7
  • PFS and overall MRD negativity (10-5 sensitivity with ≥CR) were assessed across dynamic frailty subgroups.7

Results

Efficacy
  • Across both treatment arms, 133 patients (40%) remained nonfrail from baseline to 4 years. Additionally, 69 patients (21%) switched from nonfrail to frail, 114 patients (34%) remained frail, and 15 patients (5%) shifted from frail to nonfrail. Changes in frailty level are summarized in Table: Change in Frailty Levels Yearly Across Both Treatment Arms.7

Change in Frailty Levels Yearly Across Both Treatment Arms7
Baseline
12 Months
24 Months
36 Months
48 Months
Frailty Category, %
   Nonfrail
53.7
45.7
36.6
28.0
20.1
   Frail
46.3
33.6
33.6
28.4
24.8
   Death
0
8.3
15.7
24.0
32.7
   Study Discontinuation
0
2.3
3.0
3.7
4.5
   Othera
0
10.4
11.0
16.0
17.9
Reasons for deterioration, %b
   Increase in both age and ECOG
-
2.0
5.3
7.8
7.3
   Increase in age
-
3.8
6.1
7.3
6.8
   Increase in ECOG
-
8.3
8.1
3.8
3.3
Abbreviations: ECOG, Eastern Cooperative Oncology Group
aIncludes those for whom data for frailty score calculation were not available within the correct time window.bIn 396 patients who were nonfrail at baseline.
  • MRD-negativity rates and PFS were consistently increased in the D-Rd arm across frailty groups and timepoints.7
    • For patients with worsening frailty, the 48-month PFS rate for D-Rd vs Rd was 92.9% (95% CI, 79.5-97.6) vs 65.4% (95% CI, 44.0-80.3), respectively.
    • For patients with stable frailty, the 48-month PFS rate for D-Rd vs Rd was 91.8% (95% CI, 82.7-96.2) vs 85.0% (95% CI, 69.6-93.0), respectively.
Safety

Safety Summary Based on Frailty Change at 4 Years7
Parameter
D-Rd
Rd
Frail at baseline, nonfrail at 4 years (improving)
   N
6
9
   At least 1 related serious TEAE, %a
33.3
22.2
   TEAE leading to treatment discontinuation, %
0
0
Nonfrail at baseline, frail at 4 years (worsening)
   N
43
26
   At least 1 related serious TEAE, %a
53.5
53.8
   TEAE leading to treatment discontinuation, %
18.6
34.6
Nonfrail at baseline and at 4 years (stable nonfrail)
   N
80
53
   At least 1 related serious TEAE, %a
38.8
32.1
   TEAE leading to treatment discontinuation, %
3.8
15.1
Frail at baseline and at 4 years (stable frail)
   N
74
40
   At least 1 related serious TEAE, %a
56.8
50
   TEAE leading to treatment discontinuation, %
8.1
22.5
Abbreviations: D-Rd, DARZALEX FASPRO + lenalidomide + dexamethasone; TEAE, treatment-emergent adverse event; Rd, lenalidomide + dexamethasone.aTEAEs related to at least 1 of the 4 components of study treatment.

Post Hoc Analysis of Treatment Duration in the MAIA Study

Moreau et al (2022)8 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.8
  • PFS and OS was evaluated in the following subgroups8:
    • 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.8

Results

Patient Characteristics

Baseline Characteristics and Demographics8
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).

Reasons for Lenalidomide Discontinuation8
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.8
    • 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.8
    • 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.8
  • 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.8
  • 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).8
  • 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).8
  • 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.8

PFS and OS in Patients Who Achieved VGPR by 6 Months and Converted to ≥CR by 9 or 18 Months8
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 Months8
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 Treatment8
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)
Nonhematologic
   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.

Literature Search

A literature search of MEDLINE®, Embase®, BIOSIS Previews®, and Derwent Drug File databases (and/or other resources, including internal/external databases) was conducted on 02 June 2026.

 

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(22):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. Leukemia. 2025;39(4):942-950.  
4 Facon T, Moreau P, Weisel K, et al. Supplement to: Daratumumab/lenalidomide/dexamethasone in transplant-ineligible newly diagnosed myeloma: MAIA long-term outcomes. Leukemia. 2025;39(4):942-950.  
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 Venner C, Zweegman S, Kumar S, et al. Age and frailty analyses of transplant-ineligible patients with newly diagnosed multiple myeloma in the phase 3 MAIA and CEPHEUS trials of daratumumab + lenalidomide-dexamethasone  and bortezomib + lenalidomide-dexamethasone. Poster presented at: The American Society of Clinical Oncology (ASCO) Annual Meeting; May 29-June 2, 2026; Chicago, USA.  
7 Mian H, Facon T, Cook G, et al. Dynamic frailty analysis of transplant-ineligible patients with NDMM in the phase 3 MAIA and CEPHEUS trials of daratumumab (Dara) + lenalidomide-dexamethasone (Rd) and bortezomib-Rd (VRd). Oral Presentation presented at: 22nd International Myeloma Society (IMS) Annual Meeting; September 17-20, 2025; Toronto, Canada.  
8 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.  
9 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.  
10 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.  
11 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-.  
12 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.  
13 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.  
14 Facon T, Kumar S, Plesner T, et al. 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.  
15 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.  
16 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.