Table 2.
Efficacy of novel FDA-approved combination therapies for the treatment of RRMM that do not include carfilzomib
| Author | Phase Primary end point Regimen | Patient population with RRMM | Toxicities | Results |
|---|---|---|---|---|
| San Miguel et al27 | III Randomized PFS Pd vs HD dex |
302 Pd patients vs 153 HD dex patients | Increased rate of neutropenia and pneumonia in Pd | ORR 31% Pd vs 10% HD dex Median PFS 4.0 months Pd vs 1.9 months HD dex |
| San-Miguel et al29 | III Randomized PFS FVd vs placebo + Vd |
387 FVd patients vs 381 placebo + Vd patients | Increased rate of SAE, thrombocytopenia and diarrhea in FVd | ORR 60.7% FVd vs 54.6% placebo + Vd, P=0.09 CR or nCR FVd 27.6% vs 15.7% placebo + Vd Median PFS 12.0 months FVd vs 8.1 months placebo + Vd Median OS 33.6 months FVd vs 30.4 months placebo + Vd |
| Lonial et al53 | III Randomized PFS, ORR ERd vs Rd |
321 ERd patients vs 325 Rd patients | Increased rate of grade 3–4 lymphocytopenia in ERd, increased rate of neutropenia grade 3–4 in Rd | ORR 79% in ERd vs 66% in Rd Median PFS 19.4 months in ERd vs 14.9 months in Rd |
| Moreau et al55 | III Randomized PFS NRd vs placebo + Rd |
360 NRd patients vs 362 placebo + Rd patients | Similar rate of SAE in the two groups Higher rate of rash, neuropathy and grade 3–4 thrombocytopenia in NRd | ORR 78% in NRd vs 72% in Rd CR + VGPR 48% in NRd vs 39% in Rd Median PFS 20.6 months in NRd vs 14.7 months in Rd |
| Lonial et al49 | II Randomized ORR Dara 8 vs 16 mg/kg |
Part 1: 18 patients Dara 8 mg/kg vs 16 patients Dara 16 mg/kg Part 2: 106 patients Dara 16 mg/kg |
Fatigue, anemia | ORR Dara 16 mg/kg 29.2% Median PFS Dara 16 mg/kg 3.7 months Median OS Dara 16 mg/kg 17.5 months |
| Baz et al54 | II Randomized ORR PCd vs Pd |
33 patients PCd vs 35 Pd patients | Higher rate of grade 3–4 anemia, thrombocytopenia and neutropenia in PCd | ORR 64.7% in PCd vs 38.9% in Pd Median PFS 9.5 months in PCd vs 4.4 months in Pd |
| Kumar et al57 | II ORR NCd |
78 patients NCd | Diarrhea, nausea, anemia, neutropenia | ORR 49% 12-month PFS 57.5% |
| Krishnan et al56 | I/II MTD, efficacy NPd |
32 NPd patients | Neutropenia, lymphocytopenia, thrombocytopenia | ORR 45% NPd ORR 58% in high-risk cytogenetics |
| Pozzi et al58 | I/II MTD, response BRd |
Phase I: 15 patients BRd Phase II: 23 patients BRd |
Neutropenia, anemia, thrombocytopenia, rash | ORR 47% in BRd Median PFS 10 months in BRd 2-year OS 65% in BRd |
| Plesner et al73 | I/II Safety, efficacy DRd |
Part 1: 13 patients DRd Part 2: 32 patients DRd |
Neutropenia, anemia, thrombocytopenia | ORR 81% in DRd 18-month PFS 72% in DRd 18-month OS 90% in DRd |
Abbreviations: BRd, bendamustine lenalidomide dexamethasone; CR, complete remission; Dara, daratumumab; dex, dexamethasone; DRd, daratumumab lenalidomide dexamethasone; ERd, elotuzumab lenalidomide dexamethasone; FDA, Food and Drug Administration; FVd, panobinostat bortezomib dexamethasone; HD, high dose; Id, ixazomib dexamethasone; MTD, maximum tolerated dose; NCd, ixazomib cyclophosphamide dexamethasone; nCR, near-complete remission; NPd, ixazomib, pomalidomide dexamethasone; NRd, ixazomib lenalidomide dexamethasone; ORR, overall response rate; OS, overall survival; PCd, pomalidomide cyclophosphamide dexamethasone; Pd, pomalidomide low-dose dexamethasone; PFS, progression-free survival; Rd, lenalidomide dexamethasone; RRMM, relapsed and/or refractory multiple myeloma; SAE, serious adverse events; Vd, bortezomib dexamethasone; VGPR, very good partial response.