Table 2.
Activity of Isa/Dara-KRd drug combination therapies in patients with NDMM receiving ASCT
| Study | Median follow-up, mo | ORR, % | Best response, % | MRD–, % | MRD– by cytogenetics, % | |||||
|---|---|---|---|---|---|---|---|---|---|---|
| High risk | Standard risk | Median (95% CI) PFS, mo |
PFS rate (95% CI), % |
Median (95% CI) OS, mo |
OS rate (95% CI), % |
|||||
| Isa-KRd | ||||||||||
| IsKia[40] | 20 (IQR, 18–23) | NR |
Isa-KRd: • ≥ VGPR: 94 • ≥ CR: 74 KRd: • ≥ VGPR: 94 • ≥ CR: 72 (post-consolidation) |
• Isa-KRd: 77 (10–5), 67 (10–6) • KRd: 67 (10–5), 48 (10–6) • 10–5: OR 1.67; P = 0.049 • 10–6: OR 2.29; P < 0.001 |
1 HRCA: • Isa-KRd: 76 (10–5), 72 (10–6) • KRd: 58 (10–5) ≥ 2 HRCAs: • Isa-KRd: 77 (10–5), 77 (10–6) • KRd: 53 (10–5) |
• Isa-KRd: 79 (10–5), 67 (10–6) • KRd: 70 (10–5) |
NR |
1-y: • Isa-KRd: 95 • KRd: 95 |
NR | NR |
| GMMG-CONCEPTa[41] | 44 | 95 |
• ≥ VGPR: 91 • ≥ CR: 73 (95% CI, 63–81) (post-consolidation) |
68 (10–5) (95% CI, 0.589–1) post-consolidation 82 (10–5) at any time point 73/63 (≥ 6/ ≥ 12 mo sustained MRD–) |
68 (10–5) | N/A | Not reached |
• 1-y: 86 (81–93) • 2-y: 78 (71–86) • 3-y: 69 (61–78) |
Not reached |
• 1-y: 92 (87–97) • 2-y: 84 (78–91) |
| Dara-KRd | ||||||||||
| MASTER[43, 52] | 42.2 (IQR, 34.5–46.0) |
98 • 0 HRCA: 98 • 1 HRCA: 100 • ≥ 2 HRCAs: 96 |
≥ CR: 86 • 0 HRCA: 91 • 1 HRCA: 89 • ≥ 2 HRCAs: 71 (post-consolidation) |
81 (10–5) (95% CI, 73–88) 71 (10–6) 84 (71% [95% CI, 62–79]) patients reached MRD-SURE with treatment cessation |
(10–5) • 1 HRCA: 86 (95% CI, 73–95) • ≥ 2 HRCAs: 79 (95% CI, 58–93) (10–6) • 1 HRCA: 80 • ≥ 2 HRCAs: 63 1-y sustained MRD– • 1 HRCA: 73 • ≥ 2 HRCAs: 46 |
78 (10–5) 68 (10–6) 64 (1-y sustained MRD–) |
NR |
2-y: 87 • 0 HRCA: 91 • 1 HRCA: 97 • ≥ 2 HRCAs: 58 (P < 0.001) 3-y: • 0 HRCA: 88 (78–95) • 1 HRCA: 79 (67–88) • ≥ 2 HRCAs: 50 (30–70) |
NR |
2-y: 94 • 0 HRCA: 96 • 1 HRCA: 100 • ≥ 2 HRCAs: 76 (P = 0.003) 3-y: • 0 HRCA: 94 (88–98) • 1 HRCA: 92 (86–96) • ≥ 2 HRCAs: 75 (63–85) |
| LCI-HEM-MYE-KRDD-001[44–46] | 26 (95% CI, 17–27) | 95 |
≥ VGPR: 36 ≥ CR: 56 (90% CI, 42–79) sCR: 44 (post-induction) |
62 (10–5) 41 (10–6) |
NR | NR | Not reached | 2-y: 85 (72–99) | NR | NR |
| IFM 2018–04[47, 53] | 33 |
Per-protocol population: 95 (end of induction) |
Per-protocol population: VGPR; 60 CR/sCR: 31 (end of induction) CR/sCR: 48 (before consolidation) 70 (end of early consolidation) 81 (before maintenance) |
Per-protocol population: 53 (10–5); 43 (10–6) (after induction) 97 (10–5); 94 (10–6) (before maintenance) Intention-to-treat population: 64 (10–5); 62 (10–6) (before maintenance) |
Per-protocol population: 97 (10–5); 94 (10–6) (before maintenance) |
N/A | Not reached |
• 2-y: 87 (78–87) • 30-mo: 80 (68–94) |
NR |
• 2-y: 94 (87–100) • 30-mo: 91 (82–100) |
ASCT, autologous stem cell transplant; CR, complete response; d, dexamethasone; Dara, daratumumab; HRCA, high-risk cytogenetic abnormalities; IQR, interquartile range; Isa, isatuximab; K, carfilzomib; MRD, minimal residual disease; MRD-SURE, minimal residual disease surveillance; N/A, not applicable; NDMM, newly diagnosed multiple myeloma; NR, not reported; OR, odds ratio; ORR, overall response rate; OS, overall survival; PFS, progression-free survival; R, lenalidomide; sCR, stringent complete response; VGPR, very good partial response
a99 patients were transplant eligible