Table 1 Select trials of doublet and triplet regimens in patients with transplant-ineligible NDMM and high-risk cytogenetic abnormalities
Trial | Patient population | Regimens | N | Median age (range), y | High-risk cytogenetics | Response by cytogenetics | PFS and OS by cytogenetics |
|---|---|---|---|---|---|---|---|
Retrospective study [10] | NDMM | Rd vs RD | 100 | HR: 67 (48–78) SR: 63 (32–78) | HR (n = 16): hypodiploidy, del(13q), del(17p), t(4;14), t(14;16), or plasma cell labeling index ≥3% | ORR: HR vs SR, 81 vs 89%; P = 0.56 ≥ VGPR: HR vs SR, 38 vs 45%; P = 0.36 | Median PFS: HR vs SR, 18.5 vs 36.5 mo; P < 0.001 |
NDMM | Rd vs RD | 445 | HR: 62 SR: 66 | 126 pts with FISH; HR (n = 21): t(4;14), t(14;16), or del(17p) deletions | ORR: HR vs SR, 75% vs 77% ≥ VGPR: HR vs SR, 30 vs 46% | Median PFS: HR vs SR, 11 vs 29 mo; P = 0.047 OS: HR vs SR hazard ratio, 3.48 [95% CI, 1.42–8.53]; P = 0.004 | |
NDMM TI | Rd continuous vs Rd18 vs MPT | 1623 | 73 [94% ≥ 65 y] | 762 pts with FISH; 19% HR [t(4;14), t(14;16), or del(17p)] | ORR: HR patients: 77% (Rd continuous) vs 67% (Rd18) vs 68% (MPT) SR patients: 81% (Rd continuous) vs 80% (Rd18) vs 71% (MPT) ≥ VGPR: HR patients: 30% (Rd continuous) vs 35% (Rd18) vs 11% (MPT) SR patients: 49% (Rd continuous) vs 47% (Rd18) vs 39% (MPT) | Median PFS: HR: Rd continuous, 8.4 mo Rd18, 17.5 mo MPT, 14.6 mo SR: Rd continuous, 31.1 mo Rd18, 21.2 mo MPT, 24.9 mo Median OS: HR: Rd continuous, 29.3 mo Rd18, 24.3 mo MPT, 35.5 mo SR: Rd continuous, 69.9 mo Rd18, 68.7 mo MPT, 53.6 mo | |
Ph III, SWOG S0777 [28] | NDMM without intent for immediate ASCT | RVd vs Rd | 471 | 63 [43% ≥ 65 y] | 316 pts with FISH; 33% HR [t(4;14), t(14;16), or del(17p)]a | NR | Median PFS: HR: RVd, 38 mo Rd, 16 mo P = 0.19 t(4;14): RVd, 34 mo Rd, 15 mo P = 0.96 |
NDMM TI | VMP vs MP | 682 | 71 [97% ≥ 65 y] | 168 pts in VMP with cytogenetics data; 15% HR [t(4;14), t (14;16), or del(17p)] | NR | Median OS in VMP arm only: HR vs SR cytogenetics: 40.0 mo vs not reached; P = 0.399 | |
Elderly NDMM | VMP vs VTP | 260 | HR: 72 SR: 72 [100% ≥ 65 y] | 232 pts with cytogenetics data; HR (n = 44): t(4;14), t (14;16), and/or del(17p) SR (n = 188) | ORR after induction: HR, 79% SR, 82% | Median PFS: HR vs SR, 24 vs 33 mo; P = 0.04 Median OS: HR vs SR, 38 mo vs not reached; P = 0.001 | |
Ph III GIMEMA [31] | NDMM TI | VMPT → VT vs VMP | 511 | 71 [96% ≥ 65 y] | 376 pts with cytogenetics data; 16% t(4;14), 4% t(14;16), 15% del(17p) | NR | PFS: VMP → VT vs VMP in pts with HR CAs hazard ratio, 0.98 [95% CI, 0.58–2.10]; P = 0.215 |
Elderly NDMM | Sequential or alternating VMP and Rd | 242 | NR [100% ≥ 65 y] | 174 pts with FISH; HR (n = 32): t(4;14), t (14;16), and/or del(17p) SR (n = 142) | ORR: Sequential (HR vs SR) 74 vs 79% Alternating (HR vs SR) 69 vs 86% | Median PFS: sequential (HR vs SR) 29.5 vs 31.5 mo; P = 0.9 Alternating (HR vs SR) 24 vs 33 mo; P = 0.03 Median OS: sequential (HR vs SR) 46 vs 63 mo; P = 0.1 Alternating (HR vs SR) 38.4 mo vs not reached; P = 0.002 | |
Ph III [34] | NDMM TI | MPT-T vs MPR-R | 668 | MPT-T: 72 (33% ≥ 76 y) MPR-R: 73 (34% ≥ 76 y) | 367 pts with FISH; HR (n = 174): del(17p), t(4;14), gain(1q21) | NR | PFS and OS: no significant difference in treatment with MPT-T vs MPR-R for all analyzed subgroups (HR CAs) Median PFS: gain(1q21) (MPT-T vs MPR-R) 17 vs 19 mo del(17p) (MPT-T vs MPR-R) 15 vs 15 mo t(4;14) (MPT-T vs MPR-R) 12 vs 14 mo Median OS: gain(1q21) (MPT-T vs MPR-R) 39 vs 50 mo del(17p) (MPT-T vs MPR-R) 41 vs 35 mo t(4;14) (MPT-T vs MPR-R) 23 mo vs not reached |
Retrospective institutional study [20] | NDMM TI | CyBorD vs VMP vs Vd | 122 | CyBorD: 76 VMP: 73 Vd: 77 | t(4;14), t(14;16), and p53 del, 21 pts (17%) | NR | Median PFS: HR vs SR, 11.8 vs 15.9 mo; P = 0.002 Median OS: HR vs SR, 22.4 vs 39.7 mo; P = 0.029 |
