Table 1.
Pivotal clinical trials evaluating daratumumab.
| Study name (reference) | Number of patients | Patient population | Response | Adverse events |
|---|---|---|---|---|
|
GEN 501 Phase I/II daratumumab monotherapy (4) |
32 patients in dose escalation 72 patients in cohort expansion |
RRMM patients mostly refractory to bortezomib or lenalidomide with a median of four prior lines of treatment | 16 mg/kg cohort ORR of 36%. 8 mg/kg cohort ORR of 10%. Median PFS in the 16 mg/kg cohort was 5.6 months. 65% of responding patients had not progressed after 12 months of follow-up. |
No MTD in phase I (dose escalation up to 24 mg/kg) Daratumumab administration was safe with mostly mild grade 1–2 IRRs predominantly occurring during the first infusion. Most prominent IRRs were rhinitis, cough, or dyspnea. |
|
SIRIUS Phase II daratumumab monotherapy (5) |
124 patients 18 patients: 8 mg/kg 106 patients: 16 mg/kg |
RRMM patients mostly refractory to bortezomib or lenalidomide with a median of five prior lines of treatment | 16 mg/kg cohort ORR of 29% and median PFS was 3.7 months with a 1-year OS of 65%. 8 mg/kg cohort ORR 11%. |
Similar to the GEN501 study, the most prominent side effects were IRRs of grade 1 or grade 2. |
|
GEN 503 Phase I/II daratumumab + lenalidomide + dexamethasone (13) |
13 patients in dose escalation 32 patients in cohort expansion (16 mg/kg) |
RRMM patients with a median of two prior lines of therapy | ORR was 84% in phase I and 81% in phase II with a total of 13 sCR, 3 CR, 13 VGPR, and 8 PR. In phase II, the 18-month PFS was 72% and OS was 90%. |
Grade 3–4 adverse events (≥5%) included neutropenia, thrombocytopenia, and anemia. IRRs occurred in 56% of patients after the first infusion. |
|
POLLUX Phase III Lenalidomide + dexamethasone ± daratumumab (9) |
569 patients. 286 in the DRd group and 283 in the control group |
RRMM patients with a median of one prior line of therapy. | Higher ORR in the DRd group than in the control group (92.9% versus 76.4%). The hazard ratio for disease progression or death in the daratumumab group versus the control group was 0.37. In the DRd group the MRD-negative rate at 10−5 was 22.4% versus 4.6% in the Rd group. |
Neutropenia grade 3 or 4 in 51.9% of the patients in the DRd group versus 37% in the control group. IRRs of grade 1 or 2 severity in 47.7% of the patients in the DRd group. |
|
CASTOR Phase III bortezomib + dexamethasone ± daratumumab (10) |
498 patients. 251 in the DVd group and 247 in the control group |
RRMM patients with a median of two prior lines of therapy. | Higher ORR in the DVd group than in the control group (82.9% versus 63.2%). The hazard ratio for disease progression or death in the DVd group versus the control group was 0.39. In the DVd group, the MRD-negative rate at 10−5 was 12 versus 2% in the control group. |
|Thrombocytopenia grade 3 or 4 in 45.3% of the patients in the DVd group versus 32.9% in the control group. Neutropenia grade 3–4 was 12.8% for DVd versus 4.2% for Vd. |Daratumumab-related IRRs (mostly of grade 1 or 2) occurred in 45.3% of the patients, with the majority occurring during the first infusion. |
|
EQUULEUS Phase Ib daratumumab + pomalidomide and dexamethasone (blood 130, Suppl. 1, 510) |
103 patients | RRMM patients with a median of four prior lines of therapy. | ORR was 60%, median PFS 8.8 months and median OS 17.5 months. Out of 17 patients with CR or sCR, 29% were MRD negative by NGS at 10−5. |
Neutropenia, anemia, fatigue, diarrhea, and thrombocytopenia were the most common side effects and considered to be mainly caused by pomalidomide. IRRs occurred in 50% of patients and mainly during the first infusion. One case of laryngeal edema occurred during the second infusion. |
|
ALCYONE Phase III melphalan + prednisolon + bortezomib ± daratumumab (11) |
706 patients 350 in the D-MPV group and 356 in the control group |
Newly diagnosed multiple myeloma patients who are ineligible for stem-cell transplantation. | ORR in the D-MPV group was 90.9 versus 73.9% in the control group. The hazard ratio for disease progression or death in the D-MPV group versus the control group was 0.5. In the D-MPV group, the MRD negative rate at 10−5 was 22.3 versus 6.2% in the MPV group. | Infections grade 3 or 4 in 23.1% of the patients in the D-MPV group versus 14.7% in the control group. Daratumumab-related IRRs (mostly of grade 1 or 2) occurred in 27.7% of the patients, with the majority during the first infusion. |
RRMM, relapsed/refractory multiple myeloma; ORR, overall response rate; PFS, progression-free survival; OS, overall survival; MTD, maximum tolerated dose; IRR, infusion-related reactions; MRD, minimal residual disease.