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DARZALEX FASPRO®

(daratumumab and hyaluronidase-fihj)

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DARZALEX FASPRO® (daratumumab and hyaluronidase-fihj)

Medical Information

DARZALEX FASPRO® (daratumumab and hyaluronidase)

Last Updated: 01/28/2026

SUMMARY

  • APOLLO is a phase 3 study evaluating the safety and efficacy of DARZALEX FASPRO for subcutaneous (SC) use in combination with pomalidomide and dexamethasone (D-Pd) vs pomalidomide and dexamethasone (Pd) in patients with relapsed or refractory multiple myeloma (RRMM) who received ≥1 prior treatment with both lenalidomide and a proteasome inhibitor (PI).1
    • Dimopoulos et al (2023)2 reported the final overall survival (OS) results and updated safety analysis of the APOLLO study at a median follow-up of 39.6 months. Median OS in the intent-to-treat (ITT) population was 34.4 months (95% confidence interval [CI], 23.7-40.3) vs 23.7 months (95% CI, 19.6-29.4) in the D-Pd vs Pd arm, respectively (hazard ratio [HR], 0.82; 95% CI, 0.61-1.11; P=0.20). The most common grade 3 treatment-emergent adverse events (TEAEs) (>10%) in the D-Pd arm were neutropenia (25%), anemia (17%), and leukopenia (11%), while those in the Pd arm were neutropenia (32%), anemia (21%), and thrombocytopenia (13%). The most common serious TEAE was pneumonia (D-Pd, 15%; Pd, 9%).
    • Other relevant literature related to the APOLLO study has been identified in addition to the data summarized above.3-6
  • MM-014 is a phase 2 study evaluating the safety and efficacy of D-Pd and Pd in patients with RRMM who have received 1 or 2 prior lines of therapy (LOTs) including lenalidomide.7,8
    • Bahlis et al (2024)9,10 reported the final OS in the D-Pd arm and updated results with a median follow-up of 41.9 months. For patients in the D-Pd arm, the overall response rate (ORR) was 78.6% (95% CI, 69.8-85.8). The median progression-free survival (PFS) and OS in the ITT population were 23.7 months (95% CI, 15.8-36.1) and 56.7 months (95% CI, 46.5-not reached [NR]), respectively. The most common grade 3/4 TEAEs were neutropenia (64.3%), anemia (19.6%), pneumonia (17.9%), and thrombocytopenia (14.3%).
  • Other relevant literature has been identified in addition to the data summarized above.11-15

   PRODUCT LABELING

CLINICAL DATA

Phase 3 Study of DARZALEX FASPRO in Combination with Pd in Patients with RRMM

APOLLO (MMY3013; NCT03180736)1 is an ongoing study evaluating the safety and efficacy of D-Pd vs Pd in patients with RRMM who received ≥1 prior LOT with both lenalidomide and a PI. Dimopoulos et al (2023)2 reported the final OS and updated safety analysis of D-Pd vs Pd alone in patients with RRMM in the APOLLO study with a median follow-up of 39.6 months.

Study Design/Methods

APOLLO Study Design1,2,6,16,17

Abbreviations: CD, cluster of differentiation; CR, complete response; CrCl, creatinine clearance; d, dexamethasone; D, daratumumab; D-Pd, daratumumab + pomalidomide + dexamethasone; ECOG PS, Eastern Cooperative Oncology Group performance status; HRQoL, health-related quality of life; Ig, immunoglobulin; ISS, International Staging System; LOT, line of therapy; MM, multiple myeloma; MRD, minimal residual disease; ORR, overall response rate; OS, overall survival; P, pomalidomide; Pd, pomalidomide + dexamethasone; PD, progressive disease; PFS, progression-free survival; PI, proteasome inhibitor; PK, pharmacokinetic; PO, oral; QW, every week; Q2W, every 2 weeks; Q4W, every 4 weeks; Q12W, every 12 weeks; RRMM, relapsed/refractory multiple myeloma; SC, subcutaneous; sCR, stringent complete response; VGPR, very good partial response.
aMeasurable disease was defined as: IgG MM, serum M-protein level ≥1.0 g/dL or urine M-protein level ≥200 mg/24 hours; IgA, IgD, IgE, IgM MM, serum M-protein level ≥0.5 g/dL or urine M-protein level ≥200 mg/24 hours; light chain MM for patients without measurable disease in the serum or urine, serum Ig free light chain ≥10 mg/dL and abnormal serum Ig kappa lambda free light chain ratio.
bPreinfusion medications to be administered are acetaminophen, dexamethasone, diphenhydramine, and a leukotriene inhibitor (optional). Patients with a higher risk of respiratory complications will receive postinfusion medications, including diphenhydramine, a short-acting β2 adrenergic receptor agonist, and lung disease control medications.
cPatients initially were given DARZALEX 16 mg/kg; following a protocol amendment, new patients in the D-Pd arm received DARZALEX FASPRO. Patients who had already received DARZALEX prior to this amendment may switch to DARZALEX FASPRO on day 1 of cycle 3+.
dPatients aged ≥75 years received 20 mg QW.
eFollow-up is for patients who discontinued treatment for reasons other than PD, death, loss to follow-up, or withdrawal of consent.
fMRD was assessed by next-generation sequencing using bone marrow aspirate samples obtained at screening; at the time of suspected CR or sCR; and at 6, 12, 18, 24, and Q12W after achieving CR or sCR until disease progression.
gDisease assessments were collected by a central laboratory every cycle for the first 14 months and every other month thereafter.

Results

Patient Disposition and Treatment Characteristics
  • A total of 304 patients were randomized to receive either D-Pd (n=151) or Pd (n=153) and constituted the ITT population.2 
  • For rates of patients refractory to lenalidomide, PI, and PI and lenalidomide, see Table: Demographics and Baseline Characteristics.2

Demographics and Baseline Characteristicsa,2
Characteristic
D-Pd
(n=151)
Pd
(n=153)
Age, years
   Median (range)
67 (58-72)
68 (60-73)
Sex, n (%)
   Male
79 (52)
82 (54)
   Female
72 (48)
71 (46)
Race
   White
135 (89)
137 (90)
   Black or African American
1 (1)
0
   Asian
1 (1)
1 (1)
   Other
0
1 (1)
   Unknown
14 (9)
14 (9)
Ethnicity
   Not Hispanic or Latino
134 (89)
138 (90)
   Not reported
9 (6)
9 (6)
   Hispanic or Latino
4 (3)
4 (3)
   Unknown
4 (3)
2 (1)
ECOG PS, n (%)
   0
91 (60)
77 (50)
   1
54 (36)
57 (37)
   2
6 (4)
19 (12)
ISS disease stageb, n (%)
   I
68 (45)
69 (45)
   II
50 (33)
51 (33)
   III
33 (22)
33 (22)
Time since initial diagnosis of multiple myeloma, years
   Median (IQR)
4.4 (2.7-7.1)
4.5 (2.9-6.2)
Numbers of previous lines of therapy
   Median (range)
2 (2-3)
2 (2-3)
Disease refractory to, n (%)
   Lenalidomide
120 (79)
122 (80)
   PI
71 (47)
75 (49)
   PI + lenalidomide
64 (42)
65 (42)
Abbreviations: ASCT, autologous stem cell transplantation; D-Pd, DARZALEX + pomalidomide + dexamethasone; ECOG PS, Eastern Cooperative Oncology Group performance status; IgA, immunoglobulin A; IgG, immunoglobulin G; IMiD, immunomodulatory drug; IQR, interquartile range; ISS, International Staging System; ITT, intention-to-treat; LOT, line of therapy; MM, multiple myeloma; Pd, pomalidomide + dexamethasone; PI, proteasome inhibitor.
aITT population (N=304).
bDerived from the combination of serum β2-microglobulin and albumin concentrations; higher stages indicate more severe disease.
cCytogenetic risk based on fluorescence in-situ hybridization; patients with high-risk cytogenetic profile had ≥1 high-risk abnormality (del17p, t[4;14], or t[14;16]).
  • Median duration of exposure to study treatment was 11.5 months (interquartile range [IQR], 4.6-36.1) vs 6.6 months (IQR, 3.2-15.0) in the D-Pd vs Pd arm, respectively.2
  • The median duration of follow-up was 39.6 months (IQR, 37.1-43.7).2
Efficacy
  • Median PFS on the next LOT (PFS2) was 24.4 months (95% CI, 17.1-35.7) vs 17.6 months (95% CI, 13.6-22.0) in the D-Pd vs Pd arm, respectively (HR, 0.73; 95% CI, 0.55-0.98; P=0.034).2
    • The 3-year PFS2 rate was 41.4% (95% CI, 33.1-49.4) vs 27% (95% CI, 19.8-34.8) in the D-Pd vs Pd arm, respectively.
  • Median OS was 34.4 months (95% CI, 23.7-40.3) vs 23.7 months (95% CI, 19.6-29.4) in the D-Pd vs Pd arm, respectively (HR, 0.82; 95% CI, 0.61-1.11; P=0.20).2
  • Median time to subsequent therapy was 20.0 months (95% CI, 13.8-27.1) vs 11.8 months (95% CI, 8.9-15.4) in the D-Pd vs Pd arm, respectively (HR, 0.61; 95% CI, 0.45-0.82; P=0.0008).2
  • In the safety population, a total of 48% (n=72) of patients in the D-Pd arm and 68% (n=102) of patients in the Pd arm received subsequent therapy in any line as presented in Table: Most Common (>10%) Subsequent Antimyeloma Therapies.2

Most Common (>10%) Subsequent Antimyeloma Therapiesa,2
Total Receiving Subsequent Therapy, n (%)
Any Subsequent LOT
Next Subsequent LOT
D-Pdb
(n=72)
Pd
(n=102)
D-Pdb
(n=72)
Pd
(n=102)
Dexamethasone
57 (79)
83 (81)
51 (71)
72 (71)
Carfilzomib
31 (43)
34 (33)
24 (33)
24 (24)
Cyclophosphamide
26 (36)
36 (35)
13 (18)
19 (19)
Bortezomib
20 (28)
37 (36)
10 (14)
26 (25)
Pomalidomide
14 (19)
23 (23)
7 (10)
14 (14)
Lenalidomide
11 (15)
19 (19)
10 (14)
11 (11)
Selinexor
11 (15)
2 (2)
5 (7)
0 (0)
Thalidomide
8 (11)
3 (3)
4 (6)
1 (1)
DARZALEX
5 (7)
66 (65)
4 (6)
47 (46)
Abbreviations: D-Pd, DARZALEX + pomalidomide + dexamethasone; LOT, line of therapy; Pd, pomalidomide + dexamethasone.
aSubsequent systemic antimyeloma therapy was reported based on therapeutic class, pharmacological class, and preferred term.
bD-Pd arm included all patients who received DARZALEX, regardless of the route of administration, with Pd.
Note: Percentages have been rounded and therefore might not add up to 100%.
Safety
  • No new safety concerns were reported with longer follow-up.2
  • The most common any grade and grade 3/4 TEAEs are presented in Table: Summary of Most Common TEAEs in the Safety Population.2
  • Serious TEAEs were reported in 54% (n=80) vs 40% (n=60) of patients in the D-Pd vs Pd arm, respectively.2
    • The most common serious TEAE was pneumonia (D-Pd, 15% [n=23]; Pd, 9% [n=13]).
  • Treatment modification occurred in 87% (n=130) vs 75% (n=112) of patients in the D-Pd vs Pd arm, respectively.2
  • Treatment discontinuation due to TEAEs was low among both treatment arms (D-Pd, 2% [n=3]; Pd, 4% [n=6]).2
    • Treatment discontinuation due to infection was reported in 1 (1%) patient each in both arms (D-Pd, meningoencephalitis bacterial infection; Pd, Coronavirus Disease 2019 [COVID-19]).
  • A total of 55% (n=83) vs 59% (n=91) of patients in the D-Pd vs Pd arm, respectively, died primarily due to disease progression, adverse events (AEs) unrelated to the study treatment, or COVID-19.2
  • Second primary malignancies (cutaneous, invasive, and hematological) were reported in 3% (n=4) vs 4% (n=6) of patients in the D-Pd vs Pd arm, respectively.2
    • In the D-Pd arm, cholangiocarcinoma, malignant melanoma, and squamous cell carcinoma were each reported in 1% (n=1) of patients.
    • In the Pd arm, malignant melanoma, acute myeloid leukemia, metastatic renal cell carcinoma, and thyroid neoplasm were each reported in 1% (n=1) of patients.
  • TEAEs leading to death were reported in 9% (n=13) of patients each in both arms.2
    • The most common TEAEs leading to death were pneumonia (D-Pd, 2% [n=3]; Pd, 1% [n=2]) and COVID-19 (D-Pd, 1% [n=2]; Pd, 1% [n=1]).

Summary of Most Common TEAEs in the Safety Populationa,2
TEAE, n (%)
D-Pd (n=149)
Pd (n=150)
Grade 1/2
Grade 3
Grade 4
Grade 5
Total
Grade 1/2
Grade 3
Grade 4
Grade 5
Total
Any TEAE
12 (8)
45 (30)
75 (50)
13 (9)
145 (97)
23 (15)
79 (53)
31 (21)
13 (9)
146 (97)
Hematologic TEAEs
   Anemia
30 (20)
26 (17)
1 (1)
0 (0)
57 (38)
35 (23)
31 (21)
1 (1)
0 (0)
67 (45)
   Thrombocytopenia
23 (15)
14 (9)
13 (9)
0 (0)
50 (34)
23 (15)
20 (13)
8 (5)
0 (0)
51 (34)
   Leukopenia
14 (9)
16 (11)
9 (6)
0 (0)
39 (26)
11 (7)
6 (4)
1 (1)
0 (0)
18 (12)
   Neutropenia
4 (3)
37 (25)
66 (44)
0 (0)
107 (72)
4 (3)
48 (32)
28 (19)
0 (0)
80 (53)
   Lymphopenia
3 (2)
11 (7)
8 (5)
0 (0)
22 (15)
7 (5)
3 (2)
2 (1)
0 (0)
12 (8)
   Bone marrow failure
0 (0)
0 (0)
0 (0)
1 (1)
1 (1)
0 (0)
0 (0)
0 (0)
0 (0)
0 (0)
   Febrile neutropenia
0 (0)
10 (7)
3 (2)
0 (0)
13 (9)
0 (0)
4 (3)
1 (1)
0 (0)
5 (3)
Nonhematologic TEAEs
   Upper respiratory tract infection
37 (25)
0 (0)
0 (0)
0 (0)
37 (25)
21 (14)
3 (2)
0 (0)
0 (0)
24 (16)
   Pyrexia
31 (21)
0 (0)
0 (0)
0 (0)
31 (21)
26 (17)
0 (0)
0 (0)
0 (0)
26 (17)
   Diarrhea
28 (19)
8 (5)
0 (0)
0 (0)
36 (24)
22 (15)
1 (1)
0 (0)
0 (0)
23 (15)
   Fatigue
28 (19)
15 (10)
0 (0)
0 (0)
43 (29)
31 (21)
7 (5)
0 (0)
0 (0)
38 (25)
   Asthenia
25 (17)
7 (5)
1 (1)
0 (0)
33 (22)
23 (15)
2 (1)
0 (0)
0 (0)
25 (17)
   Peripheral edema
25 (17)
0 (0)
0 (0)
0 (0)
25 (17)
14 (9)
0 (0)
0 (0)
0 (0)
14 (9)
   Bronchitis
22 (15)
0 (0)
0 (0)
0 (0)
22 (15)
15 (10)
3 (2)
0 (0)
0 (0)
18 (12)
   Dyspnea
12 (8)
3 (2)
1 (1)
1 (1)
17 (11)
12 (8)
1 (1)
0 (0)
0 (0)
13 (9)
   Lower respiratory tract infection
12 (8)
14 (9)
2 (1)
1 (1)
29 (19)
10 (7)
11 (7)
2 (1)
1 (1)
24 (16)
   COVID-19
10 (7)
5 (3)
1 (1)
2 (1)
18 (12)
2 (1)
0 (0)
0 (0)
1 (1)
3 (2)
   Hyperglycemia
9 (6)
8 (5)
1 (1)
0 (0)
18 (12)
13 (9)
7 (5)
0 (0)
0 (0)
20 (13)
   Muscular weakness
9 (6)
0 (0)
1 (1)
0 (0)
10 (7)
5 (3)
0 (0)
0 (0)
0 (0)
5 (3)
   Pneumonia
9 (6)
14 (9)
4 (3)
3 (2)
30 (20)
9 (6)
9 (6)
1 (1)
2 (1)
21 (14)
   Hypokalemia
6 (4)
6 (4)
1 (1)
0 (0)
13 (9)
8 (5)
1 (1)
0 (0)
0 (0)
9 (6)
   Hyperuricemia
3 (2)
1 (1)
1 (1)
0 (0)
5 (3)
3 (2)
0 (0)
1 (1)
0 (0)
4 (3)
   Myocardial ischemia
2 (1)
0 (0)
0 (0)
0 (0)
2 (1)
0 (0)
0 (0)
1 (1)
0 (0)
1 (1)
   Acute myocardial infarction
1 (1)
1 (1)
0 (0)
0 (0)
2 (1)
0 (0)
0 (0)
0 (0)
1 (1)
1 (1)
   General physical health deterioration
1 (1)
1 (1)
0 (0)
0 (0)
2 (1)
0 (0)
2 (1)
0 (0)
2 (1)
4 (3)
   Hyperbilirubinemia
1 (1)
0 (0)
1 (1)
0 (0)
2 (1)
1 (1)
0 (0)
0 (0)
0 (0)
1 (1)
   Lumbar vertebral fracture
1 (1)
0 (0)
1 (1)
0 (0)
2 (1)
0 (0)
2 (1)
0 (0)
0 (0)
2 (1)
   Acute pulmonary edema
0 (0)
0 (0)
1 (1)
0 (0)
1 (1)
0 (0)
0 (0)
0 (0)
0 (0)
0 (0)
   Campylobacter infection
0 (0)
0 (0)
0 (0)
1 (1)
1 (1)
0 (0)
0 (0)
0 (0)
0 (0)
0 (0)
   Cardiac arrest
0 (0)
0 (0)
0 (0)
0 (0)
0 (0)
0 (0)
0 (0)
0 (0)
1 (1)
1 (1)
   Cerebral hemorrhage
0 (0)
0 (0)
0 (0)
0 (0)
0 (0)
0 (0)
0 (0)
0 (0)
1 (1)
1 (1)
   Embolism
0 (0)
0 (0)
1 (1)
0 (0)
1 (1)
0 (0)
0 (0)
0 (0)
0 (0)
0 (0)
   Hypertensive hydrocephalus
0 (0)
0 (0)
0 (0)
0 (0)
0 (0)
0 (0)
0 (0)
0 (0)
1 (1)
1 (1)
   Liver disorder
0 (0)
0 (0)
0 (0)
1 (1)
1 (1)
0 (0)
0 (0)
0 (0)
0 (0)
0 (0)
   Pneumonia aspiration
0 (0)
0 (0)
0 (0)
1 (1)
1 (1)
0 (0)
0 (0)
0 (0)
1 (1)
1 (1)
   Respiratory failure
0 (0)
1 (1)
0 (0)
1 (1)
2 (1)
1 (1)
1 (1)
1 (1)
0 (0)
3 (2)
   Sepsis
0 (0)
1 (1)
0 (0)
1 (1)
2 (1)
0 (0)
0 (0)
1 (1)
0 (0)
1 (1)
   Septic shock
0 (0)
0 (0)
0 (0)
1 (1)
1 (1)
0 (0)
0 (0)
0 (0)
2 (1)
2 (1)
   Sudden death
0 (0)
0 (0)
0 (0)
1 (1)
1 (1)
0 (0)
0 (0)
0 (0)
0 (0)
0 (0)
   Systemic candida
0 (0)
0 (0)
0 (0)
1 (1)
1 (1)
0 (0)
0 (0)
0 (0)
0 (0)
0 (0)
   Viral pneumonia
0 (0)
0 (0)
1 (1)
0 (0)
1 (1)
0 (0)
0 (0)
0 (0)
0 (0)
0 (0)
Abbreviations: COVID-19, coronavirus disease 2019; D-Pd, DARZALEX + pomalidomide + dexamethasone; Pd, pomalidomide + dexamethasone; TEAE, treatment-emergent adverse event.
aTEAEs are listed for all grade 4 or 5 events and any grade 3 event occurring in ≥15% of patients in either treatment group (corresponding grade 1 or 2 events are listed). Each patient could have >1 event, and multiple occurrences of each event but were only counted once for each row.

Phase 2 Study of DARZALEX in Combination with Pd in Patients with RRMM

MM-014 (NCT01946477)7,8 evaluated the safety and efficacy of D-Pd and Pd in RRMM patients who have received 1 or 2 prior LOTs including lenalidomide. Bahlis et al (2024)9 reported the final OS in the D-Pd arm and updated the results with a median follow-up of 41.9 months (range, 0.4-73.1). Data specific to patients who received D-Pd are summarized.

Study Design/Methods

  • Phase 2, nonrandomized, open-label, multicenter study.7,8
  • Patients in the D-Pd arm received 28-day cycles of DARZALEX 16 mg/kg for intravenous (IV) use in combination with pomalidomide 4 mg by mouth (PO) daily (days 1-21) and dexamethasone 40 mg/day (20 mg for patients > 75 years) on days 1, 8, 15 and 22 of a 28-day cycle weekly.7,8
  • DARZALEX was administered weekly for cycles 1-2, every 2 weeks for cycles 3-6, and every 4 weeks thereafter.7
  • Key inclusion criteria for the D-Pd arm: ≥18 years of age with a documented multiple myeloma (MM) diagnosis, measurable disease (serum M-protein ≥0.5 g/dL or urine M-protein ≥200 mg/24 h), and Eastern Cooperative Oncology Group performance status (ECOG PS) ≤2, 1-2 prior lines of antimyeloma therapy, documented progressive disease during or after their last LOT, treatment with a lenalidomide-containing regimen for ≥2 consecutive cycles as their most recent regimen.8
  • Key exclusion criteria for the D-Pd arm: prior treatment with pomalidomide or DARZALEX or hypersensitivity to thalidomide, lenalidomide, dexamethasone, or monoclonal antibodies, absolute neutrophil count (ANC) <1 × 109/L, platelet count <75 × 109/L (<30 × 109/L for patients in whom ≥50% of bone marrow nucleated cells were plasma cells), corrected serum calcium >2.875 mmol/L (11.5 mg/dL), hemoglobin <8 g/dL, aspartate transaminase (AST) or alanine aminotransferase (ALT) >3.0x upper limit of normal (ULN), serum total bilirubin level >2.0 mg/dL, and severe renal impairment (creatinine clearance <30 mL/min or requiring dialysis).8
  • Primary endpoint: ORR per the modified International Myeloma Working Group (IMWG) criteria modified to include minimal response (MR).8
  • Secondary endpoints: PFS, OS, duration of response (DOR), time to response, time to progression, and safety.8
  • Key exploratory endpoints for cohort B: pharmacodynamic and mechanistic biomarkers of D-Pd; quality of life by EuroQoL 5 dimensions (EQ-5D).8

Results

Patient Characteristics

Baseline Demographics and Disease Characteristics of the D-Pd ITT Population9
Characteristic
D-Pd ITT Population
(n=112)
Age, median (range), years
66.5 (39-83)
   ≤65 years, n (%)
50 (44.6)
   >65 to ≤75 years, n (%)
50 (44.6)
   >75 years, n (%)
12 (10.7)
Male, n (%)
76 (67.9)
Female, n (%)
36 (32.1)
Race, n (%)
   White
91 (81.3)
   Black or African American
10 (8.9)
   Asian
6 (5.4)
   Other
5 (4.5)
ECOG PSa, n (%)
   0
44 (39.3)
   1
67 (59.8)
R-ISS stage, n (%)
   I
31 (27.7)
   II
52 (46.4)
   III
8 (7.1)
   NE
21 (18.8)
Time from first diagnosis, median (range), years
3.4 (0.5-11.5)
Status of most recent prior LEN-containing treatment, n (%)
   Relapsed
27 (24.1)
   Refractory
85 (75.9)
Prior lines of therapy, n (%)
   1
69 (61.6)
   2
43 (38.4)
Prior stem cell transplant, n (%)
78 (69.6)
Presence of selected cytogenetic abnormalities, n (%)
55 (49.1)b
   del13q
16 (14.3)
   del17p
7 (6.3)
   t(11;14)
6 (5.4)
   t(4;14)
11 (9.8)
   t(14;16)
4 (3.6)
   Other
39 (34.8)
Abbreviations: D-Pd, DARZALEX + pomalidomide + dexamethasone; ECOG PS, Eastern Cooperative Oncology Group performance status; ITT, intention-to-treat; LEN, lenalidomide; NE, not evaluable; R-ISS, Revised International Staging System.
aOne patient had an ECOG PS of 2.
bPercentages of patients with cytogenetic abnormalities were calculated using the ITT population (n=112) as the denominator; however, 19 (17.0%) patients had missing cytogenetic data.
Patient Disposition
  • At the data cutoff of December 16, 2022, a total of 97 (86.6%) patients were discontinued from treatment at a median follow-up of 41.9 months (range, 0.4-73.1), with the most common reason for discontinuation being progressive disease, as shown in Table: Patient Disposition.
  • A total of 75 (67.0%) patients were discontinued from the study, with the most common reason for discontinuation being death (n=50); 47/50 patients died off treatment during the long-term follow-up.9

Patient Disposition9
Parameter, n (%)
D-Pd
(n=112)
Continuing treatment
15 (13.4)
Discontinued treatment
97 (86.6)
   Disease progression
54 (48.2)
   Withdrawal by patient
23 (20.5)
   Adverse event
10 (8.9)
   Death
3 (2.7)
   Transition to commercially available treatment
2 (1.8)
   Other
3 (2.7)
   Unknown
2 (1.8)
Discontinued study
75 (67)
   Death
50 (66.7)a
   Withdrawal by patient
19 (25.3)
   Lost to follow-up
2 (2.7)
   Other
4 (5.3)
Patients continuing with follow-up
22 (19.6)
Abbreviations: D-Pd, DARZALEX + pomalidomide + dexamethasone.
aIncludes 3 patients who died on treatment and 47 patients who died during follow-up.
Efficacy

Best ORRs in the ITT Population and in the LEN-Relapsed and LEN-Refractory Subgroups9
Response, %
D-Pd ITTb Population
(N=112)
LEN-Relapsedc
(n=27)
LEN-Refractoryd
(n=85)
ORRa(95% CI)
78.6 (69.8-85.8)
81.5 (61.9-93.7)
77.6 (67.3-86.0)
CR
26.8
40.7
22.4
   VGPR
25.9
25.9
25.9
   PR
25.9
14.8
29.4
MR
8.0
7.4
8.2
SD
6.3
3.7
7.1
PD
3.6
3.7
3.5
Abbreviations: CI, confidence interval; CR, complete response; D-Pd, DARZALEX + pomalidomide + dexamethasone; ITT, intention-to-treat; LEN, lenalidomide; MR, minimal response; NE, ; ORR, overall response rate; PD, progressive disease; PR, partial response; SD, stable disease; VGPR, very good partial response.
aDue to rounding, ORR may not match the sum of individual response rates (CR + VGPR + PR).
bPatients (n=4) were NE/missing.
cPatient (n=1) was NE/missing.
dPatients (n=3) were NE/missing.
  • The median PFS in the ITT population was 23.7 months (95% CI, 15.8-36.1).9,10 
    • The median PFS in patients who had ≥1 dose modification of pomalidomide, dexamethasone, or DARZALEX was 23.7 months (95% CI, 15.9-38.2).
    • The median PFS was shorter in patients who had 1 (26.4 months [95% CI, 15.8-48.9]) vs ≥2 (40.7 months [95% CI, 18.2-NR]) dose reductions of pomalidomide or dexamethasone.
    • The median PFS was 23.5 months (95% CI, 15.6-40.7) in patients who received prior lenalidomide and a PI.
    • The median PFS in the lenalidomide-refractory and lenalidomide-relapsed groups was 23.0 months (95% CI, 14.7-34.5) and NR (95% CI, 15.6-NR), respectively.
  • The median OS in the ITT population was 56.7 months (95% CI, 46.5-NR), and death occurred in 50 (44.6%) patients.9,10 
    • The 1-year and 5-year OS rates were 91.6% (95% CI, 84.5-95.5) and 48.2% (95% CI, 37.6-58.1), respectively.
    • In patients who received 1 and 2 prior LOTs, respectively, the median OS was 56.6 months (95% CI, 41.3-NR) and NR (95% CI, 22.8-NR) and death occurred in 33 (47.8%) patients and 17 (39.5%) patients.
    • The median OS in patients with ≥1 dose modification and in those with no dose modification of pomalidomide, dexamethasone, or DARZALEX was 60.3 months (95% CI, 47.6-NR) and 16.6 months (95% CI, 6.9-NR), respectively.
    • The median OS in patients with 1 and ≥2 dose reductions of pomalidomide or dexamethasone was 56.7 months (95% CI, 24.6-NR) and NR (95% CI, 53.6-NR), respectively.
    • The median OS in the lenalidomide-relapsed and lenalidomide-refractory groups was NR (95% CI, 47.6-NR) and 53.6 months (95% CI, 28.6-NR), respectively.
    • The median OS was similar in the prespecified patient subgroups; see Table: OS by Subgroup.

OS by Subgroup10 
Baseline Characteristic
OS, Median Months
95% CI
Overall
56.7
46.5-NR
Age, years
   ≤65
NR
43.6-NR
   >65
54.4
24.1-NR
ECOG PS
   <1
59.8
47.6-NR
   >1
56.6
28.5-NR
Creatinine clearance
   <30 mL/min
-
-
   ≥30 and <45 mL/min
NA
NA
   ≥45 and <60 mL/min
NR
28.6-NR
   ≥60 mL/min
49.1
34.9-NR
   Missing
NR
20.5-NR
Prior stem cell transplant
   Yes
60.3
43.6-NR
   No
56.6
24.1-NR
Duration of the most recent LEN
   ≤24 months
41.3
21.2-56.7
   >24 months
NR
54.4-NR
Immediately prior LEN dose
   >10 mg
53.6
28.6-NR
   ≤10 mg
NR
38.4-NR
   Missing
NA
NA
Number of prior antimyeloma lines
   1
56.6
41.3-NR
   2
NR
22.8-NR
Status after most recent prior LEN
   Refractory
53.6
28.6-NR
   Relapsed
NR
47.6-NR
Baseline β2 microglobulin
   <3.5 mg/L
NR
49.1-NR
   ≥3.5 mg/L and <5.5 mg/L
54.4
21.3-NR
   ≥5.5 mg/L
21.2
13.3-NR
   Missing
NR
25.5-NR
Prior LEN + proteasome inhibitor
   Yes
54.4
42.5-NR
   No
56.7
28.6-NR
Triplet induction
   <3 agents
NR
24.1-NR
   ≥3 agents
54.4
42.5-NR
Calculated R-ISS stage
   I
NR
53.6-NR
   II
35
21.3-56.6
   III
34.4
6.1-NR
   NE
NR
41.3-NR
Cytogenetic abnormality
   High risk
35
18.7-NR
   Standard risk
56.7
38.4-NR
   NE
NR
41.3-NR
Abbreviations: CI, confidence interval; ECOG PS, Eastern Cooperative Oncology Group performance status; LEN, lenalidomide; NA, not available; NR, not reached; OS, overall survival; R-ISS, Revised International Staging System.
  • Sixty-four (57.1%) patients received subsequent therapy, and the most common subsequent therapy was bortezomib/cyclophosphamide/dexamethasone (n=7; 6.3%).
    • Only 1 patient each received chimeric antigen receptor T-cell therapy and T cell engager therapy in the regimen.
Safety
  • TEAEs in patients who received the D-Pd regimen (N=112) are presented in Table: Grade 3/4 TEAEs for the D-Pd Regimen.
    • The most common grade 3/4 TEAEs were neutropenia (72 [64.3%]), anemia (22 [19.6%]), pneumonia (20 [17.9%]), and thrombocytopenia (16 [14.3%]).9
    • Most patients (105 [93.8%]) experienced TEAEs related to pomalidomide. Drug-related TEAEs are presented in Table: Drug-Related TEAEs.

Grade 3/4 TEAEs for the D-Pd Regimen9
TEAE Observed in ≥5% of Patients, n (%)
D-Pd
(N=112)
Hematologic TEAEs
   Neutropenia
72 (64.3)
   Anemia
22 (19.6)
   Thrombocytopenia
16 (14.3)
   Febrile neutropenia
11 (9.8)
   Leukopenia
11 (9.8)
Nonhematologic TEAEs
   Pneumonia
20 (17.9)
   Decreased neutrophil count
10 (8.9)
   Hypertension
10 (8.9)
   Dyspnea
8 (7.1)
   Back pain
7 (6.3)
   Fatigue
7 (6.3)
   Decreased WBC
6 (5.4)
   Sepsis
6 (5.4)
   Chronic obstructive pulmonary disease
6 (5.4)
   Hyperglycemia
6 (5.4)
   Hypokalemia
6 (5.4)
   Atrial fibrillation
6 (5.4)
   Insomnia
6 (5.4)
Abbreviations: D-Pd, DARZALEX + pomalidomide + dexamethasone; TEAE, treatment-emergent adverse event; WBC, white blood cell.

Drug-Related TEAEs10 
TEAE, n (%)
D-Pd
(N=112)
Pomalidomide
Dexamethasone
DARZALEX
Patients reporting ≥1 related TEAE
105 (93.8)
86 (76.8)
90 (80.4)
Patients reporting ≥1 related TEAE of interest
   Neutropenia
71 (63.4)
9 (8.0)
41 (36.6)
   Thrombocytopenia
22 (19.6)
2 (1.8)
14 (12.5)
   Anemia
21 (18.8)
4 (3.6)
15 (13.4)
   Infusion-related reaction
2 (1.8)
1 (0.9)
33 (29.5)
   Infection
29 (25.9)
28 (25.0)
28 (25.0)
   Fatigue
36 (32.1)
19 (17.0)
19 (17.0)
   Nausea
9 (8.0)
7 (6.3)
9 (8.0)
   Constipation
8 (7.1)
3 (2.7)
3 (2.7)
Abbreviations: D-Pd, DARZALEX + pomalidomide + 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 12 March 2025. The search was limited to publications from 2020 to present.

 

References

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