Study | Cohort | Design | ORR/ ≥ VGPR | PFS/OS | III/IV toxicity (> 10%) | Note |
---|---|---|---|---|---|---|
Phase I/II | ||||||
Kumar et al.[122] NCT01794520 | n = 66 R/R myeloma, median 5 prior lines of therapy 46% t(11;14) | Phase 1 dose escalation venetoclax monotherapy 300-1200 mg daily | ORR 21% ≥ VGPR 15% t(11;14): ORR 40% ≥ VGPR 27% | Median TTP 2.6 months t(11;14) median TTP 6.6 months | Thrombocytopenia 26% Neutropenia 21% Anemia 14% Lymphopenia 15% |  |
Kaufman et al. [123] NCT01794520 | Phase 1: n = 20 (median 3 prior lines of therapy) Phase 2: n = 31 (median 5 prior lines of therapy) RR myeloma with t(11;14) | Phase 1/2 study of venetoclax 800 mg daily plus 20-40 mg dexamethasone on D1, 8 and 15 | Phase 1: ORR 60% ≥ VGPR 30% Phase 2: ORR 48% ≥ VGPR 36% | Phase 1: Median TTP 12.4 months Phase 2: Median TTP 10.8 months | Lymphopenia 20% Anemia 12% Neutropenia 10% Thrombocytopenia 10% |  |
Moreau et al. [124] NCT01794507 | n = 66 R/R myeloma Median of 3 prior lines of therapy 14% t(11;14) | Phase 1b study of venetoclax 50-1200 mg daily plus bortezomib and dexamethasone | ORR 67% ≥ VGPR 42% | Median TTP 9.5 months | Thrombocytopenia 29% Anemia 15% Neutropenia 14% | RP2D in combination with bortezomib and dexamethasone 800 mg daily |
Bahlis et al. [126] NCT03314181 | Part 1: R/R myeloma with t(11;14), n = 24 Part 2: RR myeloma (cytogenetically unselected), n = 24 | Phase 1 study of venetoclax 400-800 mg daily plus: Part 1: Daratumumab plus dexamethasone Part 2: Daratumumab, bortezomib and dexamethasone | Part 1: ORR 96% ≥ VGPR 96% Part 2:ORR 92% ≥ VGPR 79% | Part 1: 18-month PFS 91% Part 2: 18-month PFS 67% | Part 1: Neutropenia (21%) Hypertension (17%) Part 2: Thrombocytopenia (17%) Lymphopenia (13%) Insomnia 25% | One death due to sepsis in part 2 (in context of progressive disease) |
Costa et al.[125] NCT02899052 | n = 49 R/R myeloma (median 1 prior line of therapy) | Phase 2 study of venetoclax 400 or 800 mg plus carfilzomib and dexamethasone | ORR 80% ≥ VGPR 65% t(11;14) ORR 92% ≥ VGPR 85% | Median PFS 27 months | Lymphopenia 31% Hypertension 16% Pneumonia 12% Neutropenia 12% Hypophosphatemia 10% Diarrhea 10% Insomnia 10% |  |
Phase III | ||||||
BELLINI NCT02755597 | R/R myeloma, 1–3 prior therapies n = 97 | Phase III randomized controlled trial of bortezomib and dexamethasone plus: Placebo | ORR 68% ≥ VGPR 36% t(11;14) ORR 47% ≥ VGPR 27% | Median PFS 12 months 36 (37%) deaths at median follow up 46 months | Diarrhea 11% Thrombocytopenia 30% Anemia 15% | Increased mortality in venetoclax arm, predominantly due to infections |
 | n = 194 | Venetoclax 800 mg daily | ORR 82% ≥ VGPR 59% t(11;14) ORR 90% ≥ VGPR 70% | Median PFS 23 months 78 (40%) deaths at median follow up 46 months | Pneumonia 16% Diarrhea 15% Thrombocytopenia 15% Anemia 15% Neutropenia 18% |  |