Quadruplet regimens in randomized trials of newly diagnosed multiple myelomaa
| Trial . | Regimen . | Duration of treatment . | N . | ORR . | > = VGPR . | > = CR . | Median PFS (months) . | Median OS (months) . | Median follow up (months) . |
|---|---|---|---|---|---|---|---|---|---|
| CASSIOPEIA NCT0254138318 NDMM, age <65 y | VTd + ASCT + VTd consolidation + Dara vs no maintenance | 4 cycles induction + ASCT +2 cycles consolidation + maintenance × 2 years | 542 | 89.9% (100 days post ASCT) | 78% (100 days post ASCT) | 26% (100 days post ASCT) | NR (85% at 18 months) | NR | 18.8 |
| Dara-VTd + ASCT + Dara-VTd consolidation + Dara vs no maintenance | 543 | 92.6% (100 days post ASCT) | 83% (100 days post ASCT) | 39% (100 days post ASCT) | NR (93% at 18 months) | NR | |||
| Myeloma XI+ ISRCTN4940785238 NDMM | KRdc + ASCT + R/no maintenance | Minimum 4 cycles induction + ASCT + maintenance until progression/ tolerated | 526 | 97.7% | 91.9% | 31% | NR | - | 34.5 |
| Rdc/Tdc + ASCT + R/no maintenance | 530 | 95.3% | 79.3% | 24% | 36.2 | - | |||
| GMMG-HD7 NCT0361773139 NDMM, age <70 y | VRd + ASCT | 3 cycles + ASCT | 329 | 83.6% after induction | 60.5% after induction | 21.6% after induction | - | - | - |
| Isa-VRd + ASCT | 331 | 90% after induction | 77.3% after induction | 24.2% after induction | - | - | |||
| PERSEUS19 NCT03710603 NDMM, age <70 y | VRd + ASCT + VRd consolidation + R maintenance | 4 cycles induction + ASCT +2 cycles consolidation + maintenance until progression/ tolerated | 354 | 93.8% | 89.3% | 70.1% | NR, 67.7% at 4 years | NR | 47.5 |
| Dara-VRd + ASCT +Dara-VRd consolidation+ Dara R maintenance | 4 cycles induction + ASCT +2 cycles consolidation + maintenance until progression/ tolerated (Dara stopped if MRD− at 2 years) | 355 | 96.6% | 95.2% | 87.9% | NR, 84.3% at 4 y | NR | ||
| IMROZ21 NCT03319667 NDMM ≤80 y | VRd with R maintenance | 4 (6-week) cycles of VRd followed by 4-week cycles of Rd until disease progression | 181 | 92.3 | 82.9% | 64.1% | 45.2% at 5 y | NR | |
| Isatuximab VRd with Isa-R maintenance | 4 (6-week) cycles of Isa-VRd followed by 4-week cycles of Isa-Rd until disease progression | 264 | 91.3 | 89.1% | 74.7% | 63.2% at 5 y | NR | ||
| BENEFIT22 NCT04751877 NDMM ≤80 y | Isatuximab-Rd with Isa-R maintenance | Isa-Rd (cycle 1-12), Isa-R (cycle 13-18), Isa (cycle 19 to progression) | 135 | 78% (18 mo) | 70% (18 mo) | 31% (18 mo) | 80% at 2 y | NR | |
| Isatuximab VRd with Isa-R maintenance | Isa-Rd Bortezomib (cycle 1-12), Isa-R-bortezomib (cycle 13-18), Isa (cycle 19 to progression) | 135 | 85% (18 mo) | 82% (18 mo) | 58% (18 mo) | 91.5% at 2 y | NR |
| Trial . | Regimen . | Duration of treatment . | N . | ORR . | > = VGPR . | > = CR . | Median PFS (months) . | Median OS (months) . | Median follow up (months) . |
|---|---|---|---|---|---|---|---|---|---|
| CASSIOPEIA NCT0254138318 NDMM, age <65 y | VTd + ASCT + VTd consolidation + Dara vs no maintenance | 4 cycles induction + ASCT +2 cycles consolidation + maintenance × 2 years | 542 | 89.9% (100 days post ASCT) | 78% (100 days post ASCT) | 26% (100 days post ASCT) | NR (85% at 18 months) | NR | 18.8 |
| Dara-VTd + ASCT + Dara-VTd consolidation + Dara vs no maintenance | 543 | 92.6% (100 days post ASCT) | 83% (100 days post ASCT) | 39% (100 days post ASCT) | NR (93% at 18 months) | NR | |||
| Myeloma XI+ ISRCTN4940785238 NDMM | KRdc + ASCT + R/no maintenance | Minimum 4 cycles induction + ASCT + maintenance until progression/ tolerated | 526 | 97.7% | 91.9% | 31% | NR | - | 34.5 |
| Rdc/Tdc + ASCT + R/no maintenance | 530 | 95.3% | 79.3% | 24% | 36.2 | - | |||
| GMMG-HD7 NCT0361773139 NDMM, age <70 y | VRd + ASCT | 3 cycles + ASCT | 329 | 83.6% after induction | 60.5% after induction | 21.6% after induction | - | - | - |
| Isa-VRd + ASCT | 331 | 90% after induction | 77.3% after induction | 24.2% after induction | - | - | |||
| PERSEUS19 NCT03710603 NDMM, age <70 y | VRd + ASCT + VRd consolidation + R maintenance | 4 cycles induction + ASCT +2 cycles consolidation + maintenance until progression/ tolerated | 354 | 93.8% | 89.3% | 70.1% | NR, 67.7% at 4 years | NR | 47.5 |
| Dara-VRd + ASCT +Dara-VRd consolidation+ Dara R maintenance | 4 cycles induction + ASCT +2 cycles consolidation + maintenance until progression/ tolerated (Dara stopped if MRD− at 2 years) | 355 | 96.6% | 95.2% | 87.9% | NR, 84.3% at 4 y | NR | ||
| IMROZ21 NCT03319667 NDMM ≤80 y | VRd with R maintenance | 4 (6-week) cycles of VRd followed by 4-week cycles of Rd until disease progression | 181 | 92.3 | 82.9% | 64.1% | 45.2% at 5 y | NR | |
| Isatuximab VRd with Isa-R maintenance | 4 (6-week) cycles of Isa-VRd followed by 4-week cycles of Isa-Rd until disease progression | 264 | 91.3 | 89.1% | 74.7% | 63.2% at 5 y | NR | ||
| BENEFIT22 NCT04751877 NDMM ≤80 y | Isatuximab-Rd with Isa-R maintenance | Isa-Rd (cycle 1-12), Isa-R (cycle 13-18), Isa (cycle 19 to progression) | 135 | 78% (18 mo) | 70% (18 mo) | 31% (18 mo) | 80% at 2 y | NR | |
| Isatuximab VRd with Isa-R maintenance | Isa-Rd Bortezomib (cycle 1-12), Isa-R-bortezomib (cycle 13-18), Isa (cycle 19 to progression) | 135 | 85% (18 mo) | 82% (18 mo) | 58% (18 mo) | 91.5% at 2 y | NR |
Only regimens with any 3 of the PIs, IMiDs, or anti-CD38 MoAbs are included.
CR, complete response; Dara, daratumumab; Dara-VTd, daratumumab, bortezomib, thalidomide, dexamethasone; dex, dexamethasone; Isa, isatuximab; Isa-VRd, isatuximab, bortezomib, lenalidomide, dexamethasone; NDMM, newly diagnosed multiple myeloma; NR, not reached; ORR, overall response rate; R, lenalidomide; s/c, subcutaneous; V, bortezomib; VGPR, very good partial response; VRd, bortezomib, lenalidomide, dexamethasone.