Table 1.
Monoclonal Antibodies.
| Biologicals and Drugs | Disease Type | Recruited (Evaluable) | Efficacy Data | AE Grade 3–4 [SAE] | Trial Registration (Phase) | Reference |
|---|---|---|---|---|---|---|
| Daratumumab (Anti-CD38) | ||||||
| Daratumumab, Bortezomib, Dexamethasone vs. Bortezomib, Dexamethasone (CASTOR) | RRMM | N = 498 | ORR: 83.8% vs. 63.2% ≥VGPR: 62% vs. 29% mPFS 16.7 vs. 7.1 mo (DVd vs. Vd) |
45.7% vs. 32.9% (DVd vs. Vd) |
NCT02136134 (3) | [65,66] |
| Daratumumab, Lenalidomide, Dexamethasone vs. Lenalidomide, Dexamethasone (POLLUX) | RRMM | N = 569 | ORR: 92.9% vs. 76.4% ≥CR: 51.2% vs. 21% mPFS NR vs. 17.4 mo (DRd vs. Rd) |
88.7% vs. 76.9% (DRd vs. Rd) |
NCT02076009 (3) | [29,83] |
| Daratumumab, Carfilzomib, Dexamethasone | RRMM | N = 85 | ORR: 84%, ≥VGPR 71% | 77% [45%] | NCT01998971 (1b) | [84] |
| Daratumumab, Pomalidomide, Dexamethasone | RRMM | N = 103 | ORR: 60% mPFS 8.8 mo mOS 17.5 mo |
78% | NCT01998971 (1b) | [85] |
| Atezolizumab (PD-L1), Daratumumab, Lenalidomide/Pomalidomide | RRMM | N = 24 | ≥VGPR: 53% | 49% (0–100%) | NCT02431208 (1b) | [85] |
| Selinexor, Daratumumab, and Dexamethasome | RRMM | N = 30 (28) | ORR: 77%, ≥VGPR: 32.1% | 66% [NA] | (1b) | [86] |
| Daratumumab, Bortezomib, Cyclophosphamide, Dexamethasone (LYRA) | NDMM, RRMM | N = 101 | ORR 79% (ND), 71% (RR) VGPR: 44% (ND) 57% (RR) 12 mo PFS (87%), 12 mo OS (99%) | 56% [21%] | NCT02951819 (2) | [87] |
| Daratumumab, Bortezomib, Melphalan, Prednisone vs. Bortezomib, Melphalan, Prednisone (ALCYONE) | NDMM | N = 737 | ORR: 90.9% vs. 73.9%, ≥VGPR 72.9% vs. 49.7%, mPFS NR vs. 19.1 (DVMP vs. VMP) | 39.9% vs. 38.7% (D-VMP vs. VMP) [NR] | NCT02195479 (3) | [67] |
| Daratumumab, Bortezomib, Thalidomide, Dexamethasone vs. Bortezomib, Thalidomide, Dexamethasone (CASSEOPEIA) | NDMM | N = 1085 | CR: 39% vs. 26% (DVTd vs. VTd) | 28% vs. 15% [NA] | NCT02541383 (3) | [68] |
| Ixazomib, Lenalidomide, Dexamethasone, Daratumumab | NDMM | N = 40 (38) | ORR: 95%, ≥VGPR: 58% | 42% | NCT03012880 (2) | [88] |
| Daratumumab, Lenalidomide, Bortezomib, Dexamethasone vs. Lenalidomide, Bortezomib, Dexamethasone (GRIFFIN) | NDMM | N = 222 (16) | ORR: 100%, ≥VGPR: 100% | 88% | NCT02874742 (2) | [89] |
| Ixazomib, Daratumumab, Dexamethasone | NDMM | N = 32 (10) | ORR: 70%, VGPR: 20% | NA, 82% (unfit) 88% (frail) | NTR6297 | [90] |
| Daratumumab plus Lenalidomide and Dexamethasone for Untreated Myeloma (MAIA) | NDMM | N = 737 | ORR: 92.9% vs. 81.3%, CR; 47.6% vs. 24.9% (DRd vs. Rd) | 50% vs. 35.3% (62.9% vs. 62.7%) (DRd vs. Rd) | NCT02252172 (3) | [28] |
| Isatuximab (anti-CD38) | ||||||
| Isatuximab | RRMM | N = 84 | ORR: 23.8% | 58% (43%) | NCT02514668 | [91] |
| Isatuximab, Pomalidomide, Dexamethasone vs. Pomalidomide, Dexamethasone | RRMM | N = 307 | ORR: 60.4% vs. 35.3%, ≥VGPR: 31.8% vs. 8.5%, mPFS 11.5 vs. 6.5 mo (IsaPd vs. Pd) | 86.8% vs. 70.5% [NR} | NCT02990338 (3) | [92] |
| Isatuximab, Pomalidomide, Dexamethasone | RRMM | N = 34 | NA | 39.4% (8.8%) | NCT02283775 (1b) | [93] |
| Isatuximab, Bortezomib, Lenalidomide, Dexamethasone | NDMM | N = 22 (14) | ORR: 93% | 46%, 18% | NCT02513186 | [94] |
| MOR202 (anti-CD38) | ||||||
| MOR202 monotherapy | RRMM | N = 44 | ORR: 28% | 64% (0%) | (1/2) | [95] |
| MOR202, dexamethasone vs. MOR202, Pomalidomide, Dexamethasone vs. MOR202, Lenalidomide, Dexamethasone | RRMM | N = 56 | ORR: 28% (+dex), 65% (+len/dex), 48% (+pom/dex) |
NA | NCT01421186 (1/2a) | [96] |
| Anti-SLAMF7 antibody | ||||||
| Elotuzumab monotherapy | RRMM | N = 34 | ORR: 0% | (44.1%) | (1) | [76] |
| Elotuzumab, Lenalidomide, Dexamethasone | RRMM | N = 73 | ORR: 84% | 78% [NA] | NCT00742560 (1b/2) | [97] |
| Elotuzumab, Lenalidomide, Dexamethasone vs. Lenalidomide, Dexamethasone | RRMM | N = 646 | ORR: 79% vs. 66%, 3-year PFS 41% vs. 27%, mOS 43.7 vs. 39.6 mo (ERd vs. Rd) | 78% vs. 67% (ERd vs. Rd) | NCT01239797 (3) | [77] |
| Elotuzumab, Pomalidomide, Dexamethasone vs. Pomalidomide, Dexamethasone | RRMM | N = 117 | ORR: 53% vs. 26%, mPFS 10.3 vs. 4.7, mOS NR vs. 17.4 mo (EPd vs. Pd) | 57% vs. 60% (EPd vs. Pd) | NCT02654132 (3) | [79] |
| Elotuzumab, Thalidomide, Dexamethasone vs. Thalidomide, Dexamethasone | RRMM | N = 40 | ORR: 38%, mPFS 3.9 mo, mOS 16.3 mo | 63% [NR] | NCT01632150 (2) | [98] |
| Elotuzumab, Bortezomib, Dexamethasone vs. Bortezomib, Dexamethasone | RRMM | N = 152 (150) | ORR: 66% vs. 63% VGPR: 36% vs. 27%, mPFS 9.7 vs. 6.9 mo (EVd vs. Vd) | 71% vs. 60% [51% vs. 41] (EVd vs. Vd) | NCT01478048 (2) | [99] |
| Anti-IL6 antibody | ||||||
| Siltuximab (CNTO328), Bortezomib vs. Bortezomib | RRMM | N = 281 | ORR: 55% vs. 47% mOS 30.8 vs. 36.8 mo (SB vs. B), no efficacy | 49% vs. 29% (SB vs. B) | NCT00401843 (2) | [80] |
| Siltuximab, dexamethasone | RRMM | N = 55 (53) | ORR 19% | 36% [0] | Phase 2 | [81] |
| Siltuximab, Bortezomib, Melphalan, Prednisolone vs. Bortezomib, Melphalan, Prednisolone | NDMM | N = 106 | CR: 27% vs. 22% (SVMP vs. VMP), did not meet primary endpoint | 92% vs. 81% (SVMP vs. VMP) | NCT00911859 (2) | [100] |
| Siltuximab, Bortezomib, Lenalidomide, Dexamethasone | NDMM | N = 11 | ORR: 90.9%, ≥VGPR: 45.5% | 63.6% [9.1%] | NCT01531998 (1/2) | [101] |
| Anti-CD138 antibody | ||||||
| Indatuximab ravtansine (BT062) | RRMM | N = 29 (23) | ≥SD: 50% | Grade 1/2: 90% | (1/2) | [102] |
| Indatuximab ravtansine (BT062), lenalidomide | RRMM | N = 45 | ORR: 83% | Grade 1/2: 89% | NCT01638936 (1/2a) | [103] |
| Indatuzimab ravtansine, Lenalidomide or Pomalidomide, Dexamethasone | RRMM | N = 64 (43) | ORR: 77% | Grade 1/2: 90% | NCT01638936 (1/2a) | [104] |
| Anti-CD56 antibody | ||||||
| Lorvotuzumab Mertansine (IMGN901) monotherapy | RRMM | N = 37 (35) | ≥SD: 42.9%, PR: 5.7% | 5.4% [0] | NCT00346255 (1) | [105] |
| Lorvotuzumab mertansine, Lenalidomide, Dexamethasone | RRMM | N = 44 (41) | ORR: 59% | NA | NCT00991562 (1/2) | [106] |
| Others | ||||||
| ACTR087, SEA-BCMA | RRMM | N = 2 | 50% (1/2) | NCT03266692 (1) | [107] | |
| Tabalumab, Bortezomib, Dexamethasone | RRMM | N = 220 | ORR: 58.1% vs. 59.5% vs. 61.1%, mPFS 6.6,7.5 vs. 7.6 mo (tabalumab 100, tabalumab 300 vs. placebo) | 37% [9.1%] | NCT01602224 (2) | [82] |