Results of selected prospective clinical trials for newly diagnosed non-transplant-eligible patients carrying high-risk features
| Trial . | Regimen . | Study design (primary endpoint) . | Study definition of HR . | No. HR patients (%) . | Outcomes in HR vs SR . | PFS rates . | MRD− (%) . |
|---|---|---|---|---|---|---|---|
| SWOG-12118 | elo-VRd vs VRd | Phase 2, only HR patients, transplant ineligible (PSF) | HR-GEP, t(14;16), t(14;20), del (17p), amp(1q21), primary PCL, or elevated serum LDH (≥2 × ULN) | 100 (100) | Median FU 53 mo: no difference in median PFS | Median PFS: 31.47 mo (elo-VRd) vs 33.64 mo (VRd) P = .45 | — |
| SWOG S077786 | VRd vs Rd | Phase 3, transplant ineligible (PSF) | t(4;14), t(14;16), or del (17p) | 104 (33) | Median PFS in HR pts: 38 (VRd) vs 16 (Rd) mo*P = .19 34 (VRd) vs 17 (Rd) mo†P = .96 (median overall FU 55 mo) | Unstratified median PFS: 43 mo (VRd) vs 30 mo (Rd) | — |
| ALCYONE88,94 | D-VMp vs VMp | Phase 3, transplant ineligible (PSF) | t(4;14), t(14;16), or del(17p) | 98 (14) | PFS in HR pts NR HzR (95% CI) 0.78 (0.4-1.43) CR rate (HR) and MRD (HR) NR | HR pts: NR vs NR ITT: 36.4 mo (D-VMp) vs 19.3 mo (VMp) | HR pts: NR vs NR ITT: 28% (D-VMp) vs 7% (VMp) |
| MAIA87,92 | D-Rd vs Rd | Phase 3, transplant ineligible (PSF) | t(4;14), t(14;16), or del(17p) | 92 (12) | PFS in HR pts: NR (D-Rd) vs 29.6 mo (Rd) HzR: (95% CI) 0.57 (0.32-1.04) CR rate (HR) and MRD (HR) NR | HR pts: 45.3 (D-Rd) vs 29.6 mo (Rd) ITT: NR (D-Rd) vs 38.8 mo (Rd) | HR pts: NR vs NR ITT: 29% (D-Rd) vs 9% (Rd) |
| Trial . | Regimen . | Study design (primary endpoint) . | Study definition of HR . | No. HR patients (%) . | Outcomes in HR vs SR . | PFS rates . | MRD− (%) . |
|---|---|---|---|---|---|---|---|
| SWOG-12118 | elo-VRd vs VRd | Phase 2, only HR patients, transplant ineligible (PSF) | HR-GEP, t(14;16), t(14;20), del (17p), amp(1q21), primary PCL, or elevated serum LDH (≥2 × ULN) | 100 (100) | Median FU 53 mo: no difference in median PFS | Median PFS: 31.47 mo (elo-VRd) vs 33.64 mo (VRd) P = .45 | — |
| SWOG S077786 | VRd vs Rd | Phase 3, transplant ineligible (PSF) | t(4;14), t(14;16), or del (17p) | 104 (33) | Median PFS in HR pts: 38 (VRd) vs 16 (Rd) mo*P = .19 34 (VRd) vs 17 (Rd) mo†P = .96 (median overall FU 55 mo) | Unstratified median PFS: 43 mo (VRd) vs 30 mo (Rd) | — |
| ALCYONE88,94 | D-VMp vs VMp | Phase 3, transplant ineligible (PSF) | t(4;14), t(14;16), or del(17p) | 98 (14) | PFS in HR pts NR HzR (95% CI) 0.78 (0.4-1.43) CR rate (HR) and MRD (HR) NR | HR pts: NR vs NR ITT: 36.4 mo (D-VMp) vs 19.3 mo (VMp) | HR pts: NR vs NR ITT: 28% (D-VMp) vs 7% (VMp) |
| MAIA87,92 | D-Rd vs Rd | Phase 3, transplant ineligible (PSF) | t(4;14), t(14;16), or del(17p) | 92 (12) | PFS in HR pts: NR (D-Rd) vs 29.6 mo (Rd) HzR: (95% CI) 0.57 (0.32-1.04) CR rate (HR) and MRD (HR) NR | HR pts: 45.3 (D-Rd) vs 29.6 mo (Rd) ITT: NR (D-Rd) vs 38.8 mo (Rd) | HR pts: NR vs NR ITT: 29% (D-Rd) vs 9% (Rd) |
CI, confidence interval; CR, complete response; D-, daratumumab; elo, elotuzumab; GEP, gene expressing profiling; HR, high-risk; HzR, hazard ratio; ITT, intention-to-treat; LDH, lactate dehydrogenase; NE, not estimable; NR, not reported; NS, not significant; Rd, lenalidomide, dexamethasone; PCL, plasma cell leukemia; PFS, progression-free survival; pts, points; SR, standard risk; ULN, upper limit of normal; VMp, bortezomib, melphalan, prednisone; VRd, bortezomib, lenalidomide, dexamethasone.
In the 44 pts HR by FISH.
In the 17 pts with t(4;14) by FISH.