Table 5.
Major clinical trials and real-world studies based on daratumumab for the treatment of RRMM.
| Study | Age* | Median lines (range)/prior exposure | Response ORR/≥VGPR/≥CR | PFS/OS/DOT/DOR | Toxicity, G≥3 |
|---|---|---|---|---|---|
| MAJOR CLINICAL TRIALS | |||||
|
SIRIUS and GEN501 pooled analysis** (73) SIRIUS, Dara SA: N=106 GEN501, Dara SA: N=42 |
64 | 5 (4-7)/ Len-exposed: 98% Len-ref: 84% PI+IMiD-ref: 87% |
- 30%/14%/5% | mPFS: 3.7 mo mOS: 20 mo mDOR: 8 mo |
- Neutropenia 10% - Thrombocytopenia 14% - Anemia 18% - IRR (any G) 48% |
|
CASTOR (74–76) Dara-Vd: N=498 |
64 | 2 (1–9)/ Len-exposed: 35% Len-ref: 17% Bort-exposed: 64% |
- 85%/63%/30% | mPFS: 16.7 mo | - Neutropenia 14% - Thrombocytopenia 46% - Anemia 16% - Pneumonia 10% - PN 5% - SPM 6% |
|
POLLUX (8, 77, 78) Dara-Rd: N=569 |
65 | 1 (1-11)/ Len-exposed: 17% Bort-exposed: 84% Bort-ref: 20% |
- 93%/80%/56% | mPFS: 44.5 mo OS: 42 mo (56%) |
- Neutropenia 55% - Thrombocytopenia 15% - Febrile neutropenia 6% - Pneumonia 15% - SPM 8% |
| MAJOR REAL-WORLD STUDIES | |||||
|
Canadian Myeloma Research Group database (CMRG-DB), LeBlanc et al., 2021 (79) N=710: - Dara SA: N=100; - Dara-Vd: N=143; - Dara-Rd: N=263 |
66-70 | 3 (2-11) | Dara SA: - 45%/21%/NA Dara-Vd: - 57%/28%/NA Dara-Rd: - 84%/58%/NA |
Dara-SA: - mPFS 3.7 mo - mOS: 20 mo Dara-Vd: - mPFS 7.8 mo - mOS: 27 mo Dara-Rd: - mPFS: 26.6 mo - mOS: 32.9 mo |
NA |
|
Lovas et al., 2019 (80) Dara SA: N=48 Dara-Vd: N=19 Dara-Rd: N=29 |
62 | 3 (1-12)/ Len-exposed: 77% Bort-exposed: 97% |
Dara SA: - 46%/21%/NA Dara-Vd: - 79%/26%/NA Dara-Rd: - 81%/31%/NA |
mPFS: - Overall 17 mo - Dara-Vd 6.6 mo - Dara-Rd NR (18 mo of FU) |
- Neutropenia 2% -Thrombocytopenia 3% - Infection 15% (G5 10%) - IRR (any G) 16% |
|
GIMEMA Lazio Group, Vozella et al., 2021 (81) Dara SA: N=62 |
62 | 3 (2-8)/ Len-exposed: 90% Bort-exposed: 88% |
46%/17%/5% | mPFS: 2.7 mo mOS: 22 mo |
- Neutropenia 5% - Anemia 15% - Thrombocytopenia 12% - IRR 6% (any G 15%) |
|
Markovic et al., 2021 (82) Dara SA: N=44 |
65 | 4 (2-9)/ PI+IMiD-ref: 75% |
37%/27%/NA | mPFS: 7.2 mo mOS: 7.8 mo |
- Anemia 22% - Thrombocytopenia 9% - IRR 13% (any G 27%) |
|
Jullien et al., 2019 (83) Dara SA: N=41 |
68 | 4 (2-9)/ PI+IMiD-ref: 58% |
24%/5%/0% | mPFS: 1.9 mo mOS: 6.5 mo |
- Anemia 12% - Thrombocytopenia 12% - Infection 10% - IRR 3% (any G 29%) |
|
Polish Myeloma Group, Salomon-Perzyński et al., 2019 (84) Dara SA: N=30 |
63 | 4 (2-10)/ PI+IMiD-ref: 50% |
43%/28%/21% | mPFS: 9.5 mo mOS: 13.8 mo |
- Neutropenia 13% - Anemia 16% - Pneumonia 10% - IRR 6% (any G 20%) |
|
Optum’s deidentified electronic health record (EHR) database, Davies et al., 2021 (52) Dara-Rd: N=99 Dara-Pd: N=149 |
Dara-Rd: 70 Dara-Pd: 68 |
NA/ Dara-Rd: 42% ≥4 lines Dara-Pd: 72% ≥4 lines PI+IMiD-exposed: 67% and 86%, respectively (ref: 31% and 68%, respectively) |
– | mDOR: - Dara-Rd: NA - Dara-Pd: 6 mo mTTNT: - Dara-Rd: NA - Dara-Pd: NA |
NA |
*Age: median age. **Different treatment schedules were included in the phase I/II GEN501 trial. For the sake of clarity, all information regarding the different groups is reported together.
RRMM, relapsed/refractory multiple myeloma; Dara, daratumumab; SA, as a single agent; V, Bort, bortezomib; d, dexamethasone; N, number; R, Len, lenalidomide; GIMEMA, Italian Adult Haematological Diseases Group; P, pomalidomide; PI, proteasome inhibitor; IMiD, immunomodulatory drug; ref, refractory; ORR, overall response rate; ≥VGPR, at least a very good partial response; ≥CR, at least a complete response; NA, not available; PFS, progression-free survival; OS, overall survival; DOT, duration of treatment; DOR, duration of response; mDOR, median DOR; mPFS, median PFS; mOS, median OS; mDOT, median DOT; mo, months, FU, follow-up; NR, not reached; G, grade; IRR, infusion-related reaction; PNP, peripheral neuropathy; SPM, second primary malignancy.