Selected published/ongoing/planned clinical trials specifically dedicated to patients with high-risk ND MM according to prespecified different definitions
| Trial . | Regimen . | Study design (primary endpoint) . | Study definition of HR . | Results . |
|---|---|---|---|---|
| OPTIMUM57,119 | Dara-CVRd vs VRd | Phase 2b, first-line TE and TNE NDMM (MRD 100 d post-ASCT and PFS) | Two or more of: t[4;14], or t[14;16], t(14;20), del(1p32) gain(1q) or del(17p), HR-GEP, PCL (>20% cPCs) | 93% ORR, 52% CRs, 35% VGPRs, 5% PR MRD 50% |
| UK-MRA Myeloma XV (RADAR) (EudraCT: 2019- 001258-25) | Cy-PI-RD + ASCT followed by len ± PI ± Isa/12-mo Isa* | Phase 2, first-line TE and TNE NDMM (MRD and response) | t(4;14), t(14;16), t(14;20), del(17p), gain(1q) | Ongoing study |
| GMMG-CONCEPT90 | Isa-KRd in induction, consolidation, and maintenance ± ASCT | Phase 2, TE (arm A) and TNE (arm B) NDMM (MRD− 10−5 postconsolidation) | del17p or t(4;14) or t(14;16) or >3 copies 1q21 and ISS 2 or 3 stage disease | Interim analysis on 50 pts: 46 (A), 4 (B) ORR, ≥PR: 100%, ≥VGPR: 90%, CR/sCR: 46% MRD+: 20/33 (61%), MRD−: 11/33 (33%) |
| IRD Study (Nordic Myeloma Study Group) (HR-Maintenance Arm)120 | IRd induction and consolidation followed by IR maintenance (HR arm) | Phase 2, TE NDMM (MRD <0.01%) | t(4;14), del(17p) (60%), t(14;16), t(14;20), gain(1q) | Ongoing study |
| ANTARES EMN19 (NCT04166565) | CyBorD ± ASCT | Phase 2, NDMM or first relapse MM with EMD (≥CR) | EMD associated with high LDH level, del(17p) and HR-GEP | Ongoing study |
| SWOG 12119 | VRd vs VRd-Elo | Phase 2, TNE NDMM (PSF) | HR-GEP, t(14;16), t(14;20), del (17p), amp(1q21), primary PCL, or elevated serum LDH (≥2 × ULN) | Median FU 53 mo PFS 33.6 vs 31.5 mo (P = .449) OS NR vs 68 mo (P = .239) ORR 88% (44) vs 83% (39) ≥CR 6 vs 2.1% |
| EMN12121 | KRd ± ASCT followed by KR maintenance | Phase 2, no-randomized, TE and TNE pPCL patients (PFS) | (del(17p), t(4;14), t(14;16), del(1p), ampl(1q), ISS stage 3; elevated LDH | 14/15 pts ≤65 y received the planned 4 cycled of induction (1/15 off protocol for PD) ORR ≥ PR 93% ORR ≥ VGPR 80% (≥ CR 33%) (13% PR, 47% VGPR, 20% CR, 13% sCR) 0% mortality during induction No discontinuation due to toxicity AEs only first cycle KRd (decreased thereafter) |
| Intergroupe Francophone du Myelome 2018-04 (NCT03606577) | Dara-KRd for induction and consolidation + double ASCT | Phase 2, nonrandomized, NDMM TE | del(17p), or t(14;16) or t(4;14) | Ongoing study |
| Trial . | Regimen . | Study design (primary endpoint) . | Study definition of HR . | Results . |
|---|---|---|---|---|
| OPTIMUM57,119 | Dara-CVRd vs VRd | Phase 2b, first-line TE and TNE NDMM (MRD 100 d post-ASCT and PFS) | Two or more of: t[4;14], or t[14;16], t(14;20), del(1p32) gain(1q) or del(17p), HR-GEP, PCL (>20% cPCs) | 93% ORR, 52% CRs, 35% VGPRs, 5% PR MRD 50% |
| UK-MRA Myeloma XV (RADAR) (EudraCT: 2019- 001258-25) | Cy-PI-RD + ASCT followed by len ± PI ± Isa/12-mo Isa* | Phase 2, first-line TE and TNE NDMM (MRD and response) | t(4;14), t(14;16), t(14;20), del(17p), gain(1q) | Ongoing study |
| GMMG-CONCEPT90 | Isa-KRd in induction, consolidation, and maintenance ± ASCT | Phase 2, TE (arm A) and TNE (arm B) NDMM (MRD− 10−5 postconsolidation) | del17p or t(4;14) or t(14;16) or >3 copies 1q21 and ISS 2 or 3 stage disease | Interim analysis on 50 pts: 46 (A), 4 (B) ORR, ≥PR: 100%, ≥VGPR: 90%, CR/sCR: 46% MRD+: 20/33 (61%), MRD−: 11/33 (33%) |
| IRD Study (Nordic Myeloma Study Group) (HR-Maintenance Arm)120 | IRd induction and consolidation followed by IR maintenance (HR arm) | Phase 2, TE NDMM (MRD <0.01%) | t(4;14), del(17p) (60%), t(14;16), t(14;20), gain(1q) | Ongoing study |
| ANTARES EMN19 (NCT04166565) | CyBorD ± ASCT | Phase 2, NDMM or first relapse MM with EMD (≥CR) | EMD associated with high LDH level, del(17p) and HR-GEP | Ongoing study |
| SWOG 12119 | VRd vs VRd-Elo | Phase 2, TNE NDMM (PSF) | HR-GEP, t(14;16), t(14;20), del (17p), amp(1q21), primary PCL, or elevated serum LDH (≥2 × ULN) | Median FU 53 mo PFS 33.6 vs 31.5 mo (P = .449) OS NR vs 68 mo (P = .239) ORR 88% (44) vs 83% (39) ≥CR 6 vs 2.1% |
| EMN12121 | KRd ± ASCT followed by KR maintenance | Phase 2, no-randomized, TE and TNE pPCL patients (PFS) | (del(17p), t(4;14), t(14;16), del(1p), ampl(1q), ISS stage 3; elevated LDH | 14/15 pts ≤65 y received the planned 4 cycled of induction (1/15 off protocol for PD) ORR ≥ PR 93% ORR ≥ VGPR 80% (≥ CR 33%) (13% PR, 47% VGPR, 20% CR, 13% sCR) 0% mortality during induction No discontinuation due to toxicity AEs only first cycle KRd (decreased thereafter) |
| Intergroupe Francophone du Myelome 2018-04 (NCT03606577) | Dara-KRd for induction and consolidation + double ASCT | Phase 2, nonrandomized, NDMM TE | del(17p), or t(14;16) or t(4;14) | Ongoing study |
MRD− only.
AEs, adverse events; ASCT, autologous stem-cells transplantation; CR, complete response; CyBorD, cyclophosphamide, bortezomib and dexamethasone; Cy-PI-RD, cyclophosphamide, pomalidomide, lenalidomide, and dexamethasone; CVRd, bortezomib, lenalidomide, cyclophosphamide, and dexamethasone; Dara, daratumumab; DSMM, Deutsche Studiengruppe MM; Elo, elotuzumab; EMD, extra-medullary disease; GEP, gene expressing profile; HR, high-risk; IRd, isatuximab, lenalidomide, and dexamethasone; Isa, isatuximab; KRd, carfilzomib, lenalidomide, and dexamethasone; LDH, lactate dehydrogenase; len, lenalidomide; MRD, minimal residual disease; NR, not reported; ORR, overall response rate; OS, overall survival; PCL, plasma cell leukemia; Pd, pomalidomide and dexamethasone; PFS, progression-free survival; PR, partial response; sCR, stringent complete response; TE, transplant eligible; TNE, transplant noneligible; TPP, time to progression; ULN, upper limit of normal; VGPR, very good partial response; VRd, bortezomib, lenalidomide and dexamethasone.