Table 2.
List of phase III trials exploring naked mAbs in multiple myeloma (MM)
| Molecule (Target) | Study | Treatment Schema | Setting | Toxicities (≥G3) | ORR (MRD Negativity Rate, NGS, Sensitivity 10−5) | PFS | OS |
|---|---|---|---|---|---|---|---|
| Daratumumab (anti-CD38) | CASTOR [48] NCT02136134 |
Dara-Vd vs. Vd | RRMM | Thrombocytopenia (45.7% vs. 32.9%); pneumonia (9.9% vs. 10.1%); hypertension (6.6% vs. 0.8%) | 83.8% vs. 63.2% (11.6% vs. 2.4%) | 16.7 vs. 7.1 | NA |
| Daratumumab (anti-CD38) | POLLUX [49] NCT02076009 |
Dara-Rd vs. Rd | RRMM | Neutropenia (55.5% vs. 41.6%); pneumonia (15.2% vs. 10%); diarrhea (9.9% vs. 3.9%); | 92.9% vs. 76.4% (30.4% vs. 5.3%) | 44.5 vs. 17.5 | 1-year OS 92.1% vs. 86.8% |
| Daratumumab (anti-CD38) | CANDOR [50] NCT03158688 |
Dara-Kd vs. Kd | RRMM | Thrombocytopenia (24% vs. 16%); respiratory tract infection (29% vs. 16%); hypertension (18% vs. 13%) |
84% vs. 75% (14% vs. 3%) | NR vs. 15.8 | NR vs. NR |
| Daratumumab (anti-CD38) | ALCYONE [51] NCT02195479 |
Dara-VMP vs. VMP |
NDMM | Neutropenia (39.9% vs. 38.7%); infections (23.1% vs. 14.7%); any infusion-related reaction (4.9% vs. na) | 90.9% vs. 73.9% (22.3% vs. 6.2%) | NR vs. 18.1 | 36-month rate: 78% vs. 67.9% |
| Daratumumab (anti-CD38) | MAIA [52] NCT02252172 |
Dara-Rd vs. Rd | NDMM | Neutropenia (50% vs. 35.3%); infections (32.1% vs. 23.3%); fatigue (8% vs. 3.8%) |
92.9% vs. 81.3% (24.2% vs. 7.3%) | NR vs. 31.9 | NA |
| Daratumumab (anti-CD38) | CASSIOPEIA [53] NCT02541383 |
Dara-VTd vs. VTd | NDMM | Neutropenia (28% vs. 15%); stomatitis (13% vs. 16%); peripheral sensory neuropathy (9% vs. 9%) | 92.6% vs. 89.9% (64% vs. 44%) * | NA | NA |
| Daratumumab (anti-CD38) | COLUMBA [54] NCT03277105 |
Subcutaneous vs. intravenous administration of daratumumab | RRMM | Thrombocytopenia (14% vs. 13%); hypertension (3% vs. 6%); febrile neutropenia (2% vs. 3%); back pain (2% vs. 3%) | 41% vs. 37% | 5.6 vs. 6.1 | NA |
| Isatuximab (anti-CD38) | ICARIA-MM [55] NCT02990338 |
Isa-Pd vs. Pd | RRMM | Neutropenia (85% vs. 70%); pneumonia (16% vs. 14%); dyspnea (4% vs. 1%) | 60% vs. 35% (5% vs. 0%) |
11.5 vs. 6.5 | NA |
| Isatuximab (anti-CD38) | IKEMA [56] NCT03275285 |
Isa-Kd vs. Kd | RRMM | Respiratory infections (32.2% vs. 23.8%); cardiac failure (4% vs. 4.1%); thrombocytopenia (29.9% vs. 23.8%); neutropenia (19.2% vs. 7.4%) kd, respectively. | 86.6% vs. 82.9% (29.6% vs. 13%) | NR vs. 19.2 | NA |
| Elotuzumab (anti-SLAMF7) | ELOQUENT-2 [57] NCT01239797 |
Elo-Rd vs. Rd | RRMM | Lymphocytopenia (79% vs. 49%); infections (33% vs. 26%); pneumonia (14% vs. 10%) | 79% vs. 66% | 19.4 vs. 14.9 | 48 vs. 40 |
* Flow. Abbreviations: G, grade; ORR, overall response rate; MRD, minimal residual disease; NGS, next-generation sequencing; PFS, progression-free survival; OS, overall survival; RRMM, relapsed/refractory multiple myeloma; NDMM, newly diagnosed multiple myeloma; Dara, daratumumab; d, dex, dexamethasone; V, bortezomib; R, lenalidomide; K, carfilzomib; VMP, bortezomib-melphalan-prednisone; T, thalidomide; P, Poma, pomalidomide; SLAMF7, signaling lymphocytic activation molecule family 7; Elo, elotuzumab; NR, not reached; NA, not available.