Phase 3 studies evaluating PI-based triplets in early RRMM
| . | CASTOR27,69 . | OPTMISSM19 . | PANORAMA 170,71 . | CANDOR34 . | IKEMA35 . | BOSTON72 . |
|---|---|---|---|---|---|---|
| No. of patients | 498 | 559 | 768 | 466 | 302 | 402 |
| Regimen | dara-Vd vs Vd | PVd vs Vd | Pano-Vd vs Vd | dara-Kd vs Kd | isa-Kd vs Kd | SVd vs Vd |
| Patient population | • At least 1 prior line of therapy; bort-refractory patients were excluded• Creatinine clearance ≥20 mL/min | • 1-3 prior lines, including ≥2 cycles of lenalidomide• Patients with severe renal impairment requiring dialysis were excluded | • 1-3 prior lines of therapy; PI-refractory patients were excluded• Creatinine clearance ≥60 mL/min | • 1-3 prior lines of therapy• Creatinine clearance ≥20 mL/min | • 1-3 prior lines of therapy• No prior therapy with carfilzomib• Creatinine clearance ≥15 mL/min | • 1-3 prior lines of therapy• At least a PR to a prior PI, if received• Creatinine clearance ≥20 mL/min |
| Prior len % / len-refractory % | 42.0 / NA | 100 / 69.9 | 20.4 / NA | 42.3 / 33.0 | NA / 32.8 | 38.3 / NA |
| Prior bort % / bort-refractory % | 65.5 / NA | 72.3 / 10.0 | 43.0 / NA | 90.3 / 29.0 | 89.7 / 33.1* | 69.4 / NA |
| CD38 antibody exposed % | 0? | 0? | 0? | 0? | 0? | 4.2 |
| Median follow-up, mo | 19.4 | 15.9 | For PFS: 6.5For OS: not reported | 16.9 | 20.7 | 13.2 and 16.5 mo in SVd and Vd arms, respectively |
| ≥PR % | 83.8 vs 63.2 | 82.2 vs 50.0 | 60.7 vs 54.6 | 84.3 vs 74.7 | 86.6 vs 82.9 | 76.4 vs 62.3 |
| (s)CR % | 28.8 vs 9.8 | 15.7 vs 4.0 | 11 vs 6 | 28.5 vs 10.4 | 39.7 vs 27.6 | 16.9 vs 10.6 |
| HR PFS (95% CI) | 0.31 (0.24-0.39);P < .0001 | 0.61 (0.49-0.77);P < .0001 | 0.63 (0.52-0.76);P < .0001 | 0.63 (0.46-0.85);P = .0014 | 0.53 (0.32-0.89);P = .007 | 0.70 (0.53-0.93);P = .0075 |
| HR OS (95% CI) | OS data immature | OS data immature; 0.98 (0.73-1.32);P = .89 | 0.94 (0.78-1.14);P = .54 | 0.75 (0.49-1.13);P = .084 | OS data immature | 0.84 (0.57-1.23);P = .19 |
| . | CASTOR27,69 . | OPTMISSM19 . | PANORAMA 170,71 . | CANDOR34 . | IKEMA35 . | BOSTON72 . |
|---|---|---|---|---|---|---|
| No. of patients | 498 | 559 | 768 | 466 | 302 | 402 |
| Regimen | dara-Vd vs Vd | PVd vs Vd | Pano-Vd vs Vd | dara-Kd vs Kd | isa-Kd vs Kd | SVd vs Vd |
| Patient population | • At least 1 prior line of therapy; bort-refractory patients were excluded• Creatinine clearance ≥20 mL/min | • 1-3 prior lines, including ≥2 cycles of lenalidomide• Patients with severe renal impairment requiring dialysis were excluded | • 1-3 prior lines of therapy; PI-refractory patients were excluded• Creatinine clearance ≥60 mL/min | • 1-3 prior lines of therapy• Creatinine clearance ≥20 mL/min | • 1-3 prior lines of therapy• No prior therapy with carfilzomib• Creatinine clearance ≥15 mL/min | • 1-3 prior lines of therapy• At least a PR to a prior PI, if received• Creatinine clearance ≥20 mL/min |
| Prior len % / len-refractory % | 42.0 / NA | 100 / 69.9 | 20.4 / NA | 42.3 / 33.0 | NA / 32.8 | 38.3 / NA |
| Prior bort % / bort-refractory % | 65.5 / NA | 72.3 / 10.0 | 43.0 / NA | 90.3 / 29.0 | 89.7 / 33.1* | 69.4 / NA |
| CD38 antibody exposed % | 0? | 0? | 0? | 0? | 0? | 4.2 |
| Median follow-up, mo | 19.4 | 15.9 | For PFS: 6.5For OS: not reported | 16.9 | 20.7 | 13.2 and 16.5 mo in SVd and Vd arms, respectively |
| ≥PR % | 83.8 vs 63.2 | 82.2 vs 50.0 | 60.7 vs 54.6 | 84.3 vs 74.7 | 86.6 vs 82.9 | 76.4 vs 62.3 |
| (s)CR % | 28.8 vs 9.8 | 15.7 vs 4.0 | 11 vs 6 | 28.5 vs 10.4 | 39.7 vs 27.6 | 16.9 vs 10.6 |
| HR PFS (95% CI) | 0.31 (0.24-0.39);P < .0001 | 0.61 (0.49-0.77);P < .0001 | 0.63 (0.52-0.76);P < .0001 | 0.63 (0.46-0.85);P = .0014 | 0.53 (0.32-0.89);P = .007 | 0.70 (0.53-0.93);P = .0075 |
| HR OS (95% CI) | OS data immature | OS data immature; 0.98 (0.73-1.32);P = .89 | 0.94 (0.78-1.14);P = .54 | 0.75 (0.49-1.13);P = .084 | OS data immature | 0.84 (0.57-1.23);P = .19 |
bort, bortezomib; CI, confidence interval; CR, complete response; dara-Kd, daratumumab-carfilzomib-dexamethasone; dara-Vd, daratumumab-bortezomib-dexamethasone; HR, hazard ratio; isa-Kd, isatuximab-carfilzomib-dexamethasone; Kd, carfilzomib-dexamethasone; NA, not available; Pano-Vd, panobinostat-bortezomib-dexamethasone; PI, proteasome inhibitor; PR, partial response; PVd, pomalidomide-bortezomib-dexamethasone; SVd, selinexor-bortezomib-dexamethasone; Vd, bortezomib-dexamethasone.
Prior PIs/PI-refractory.