Table 4.
Activity of Isa/Dara-KRd in patients with NDMM not receiving ASCT
| Study | Median follow-up, mo | ORR, % | Best response, % | MRD–, % | MRD– by cytogenetics, % | Median (95% CI) PFS, mo | PFS rate (95% CI), % |
Median (95% CI) OS, mo | OS rate (95% CI), % |
|
|---|---|---|---|---|---|---|---|---|---|---|
| High risk | Standard risk | |||||||||
| Isa-KRd | ||||||||||
| GMMG-CONCEPTa[41] | 33 |
89 (post-consolidation) |
• ≥ VGPR: 89 • ≥ CR: 58 |
54 (10–5) 69 (10–5) at any time point 54/46 (≥ 6/ ≥ 12 mo sustained MRD–) |
54 (10–5) | N/A | Not reached |
• 1-y: 75 (60–95) • 2-y: 63 (46–85) • 3-y: 58 (42–82) |
Not reached |
• 1-y: 84 (70–100) • 2-y: 71 (55–92) |
| SKylaRkb[[42,54]] | 26 | 100 |
C8: • ≥ VGPR: 98 • ≥ CR: 65 (post-consolidation) |
C8: 72 (10–5) 19 (10–6) |
NR | NR | NR |
• 1-y: 98 (86–100) • 2-y: 91 (83–100) |
NR |
• 1-y: 98 (86–100) • 2-y: 96 (90–100) |
| Dara-KRd | ||||||||||
| GEM2017FIT[48] | 33 |
VMP-Rd: 87 (P < 0.0001) Dara-KRd: 89 (P < 0.0001) KRd: 89 (P < 0.0001) (end of induction) |
≥ CR: • VMP-Rd: 40 (P < 0.0001) • Dara-KRd: 61 (P < 0.0001) • KRd: 59 (P < 0.0001) |
(10–5) • VMP-Rd: 32 (P < 0.0001) • Dara-KRd: 79 (P < 0.0001) • KRd: 69 (P < 0.0001) (10–6) • VMP-Rd: 24 (P < 0.0001) • Dara-KRd: 75 (P < 0.0001) • KRd: 59 (P < 0.0001) |
NR | NR | NR |
18 mo: • VMP-Rd: 79 • Dara-KRd: 87 • KRd: 87 |
NR |
18 mo: • VMP-Rd: 91 • Dara-KRd: 90 • KRd: 95 |
| MANHATTAN[49] | 20.3 (95% CI, 19–22) |
100 (end of C8) |
• ≥ VGPR: 95 • ≥ CR: 95 |
71 (54–83) (10–5) 88 (1-y sustained MRD–)c |
OR, 1.7 (95% CI, 0.36–8.6); P = 0.50 vs standard risk | N/A | NR |
1-y: 98 (93–100) |
NR | 1-y: 100 |
| UC-IRB17-1097[50] | 27 |
95 (end of C8 induction) sCR and/or MRD–: 75 (95% CI, 61–89) |
• ≥ VGPR: 95 • sCR: 68 |
59 (10–5) 35 (10–6) Best MRD– 65 (10–5), 53 (10–6) 40 (1-y sustained MRD–)d |
NR | NR | NR |
3-y: 85 • 0 HRCA: 100 • 1 HRCA: 92 • ≥ 2 HRCAs: 60 |
NR | 3-y: 95 |
| MMY1001[51] | 23.3 (6.9–27.7) |
100 (end of C13) |
• ≥ VGPR: 86 • ≥ CR: 67 |
75 (10–5) (for 6 of 8 patients who achieved ≥ CR) |
NR | NR | Not reached |
1-y: 95 (71–99) |
NR | NR |
ASCT, autologous stem cell transplant; C, cycle; CR, complete response; d, dexamethasone; Dara, daratumumab; HRCA, high-risk cytogenetic abnormalities; Isa, isatuximab; ITT, intention-to-treat; K, carfilzomib; MRD, minimal residual disease; 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; SCT, stem cell transplant; VGPR, very good partial response; VMP, bortezomib, melphalan, and prednisone
a26 patients were transplant ineligible
bThe SKylaRk trial included transplant-eligible patients, but SCT was deferred in most patients (89%; 40/45 patients who were evaluable after induction and consolidation). A total of 36 patients completed C8 of therapy and were evaluable for MRD measurement. PFS and OS were evaluated in the ITT population (N = 50)
cPatients who were assessed for MRD at 1-y follow-up
dMRD < 10–5 on two or more instances ≥ 1 y apart. The denominator includes patients with trackable MRD and ≥ 1 y of MRD follow-up if they had at least one MRD negative result