PFS and OS data for studies in patients with NDMM included in the meta-analysis
| Study/sponsor . | Treatment, n (%) . | N . | Median follow-up,∗ mo . | Median PFS, mo . | Median OS, mo . | MRD assay† . |
|---|---|---|---|---|---|---|
| TE NDMM | ||||||
| Randomized phase 3 trial for previously untreated MM to evaluate 2 regimens of bortezomib–based induction therapy and lenalidomide consolidation followed by lenalidomide maintenance treatment (MM5)/University Hospital Heidelberg21 https://www.clinicaltrialsregister.eu/ctr-search/trial/2010-019173-16/DE | A1‡: 149 (24.8%) A2‡: 151 (25.1%) B1‡: 150 (25%) B2‡: 151 (25.1%) | 601 | 57.1 (IQR, 44.4-64) | 40.5 (95% CI, 36.5-43.2) | NR | MFC |
| Phase 2, randomized, open-label study comparing D-RVd vs RVd in subjects with NDMM eligible for high-dose chemotherapy and autologous stem cell transplantation (GRIFFIN-MMY2004)/Janssen R&D23 NCT02874742 | D-RVd: 120 (53.8%) RVd: 103 (46.2%) | 223 | 25.4 (IQR, 22.1-28.3) | NR (95% CI, 34.1-NR) | NR | NGS |
| Study of daratumumab in combination with bortezomib (Velcade), VTD in the first line treatment of TE subjects with NDMM (CASSIOPEIA-MMY3006)/Intergroupe Francophone du Myelome24,25 NCT02541383 | D-VTd: 543 (50%) VTd: 542 (50%) | 1085 | 18.2 (IQR, 13.7-24) | NR | NR | NGS |
| TIE NDMM | ||||||
| A randomized, open-label phase 3 study of KMP vs VMP in TIE patients with NDMM (CLARION)/Amgen15 NCT01818752 | KMP: 428 (50.2%) VMP: 425 (49.8%) | 853 | 22.3 (IQR, 19.1-27.6) | 22.2 (95% CI, 21-24.2) | NR | MFC |
| A phase 3, randomized, controlled, open-label study of Velcade VMP compared with daratumumab in combination with VMP (D-VMP) in subjects with previously untreated MM who are ineligible for high-dose therapy (ALCYONE-MMY3007) Janssen R&D26,27 NCT02195479 | D-VMP: 350 (49.6%) VMP: 356 (50.4%) | 706 | 39.9 (IQR, 37.4-42.9) | 24 (95% CI, 21.6-27.4) | NR | NGS |
| A phase 3, randomized, double-blind, multicenter study comparing oral MLN9708 plus Rd vs placebo plus Rd in adult patients with NDMM (TOURMALINE-MM2)/Takeda18 NCT01850524 | IRd: 351 (49.8%) Rd: 354 (50.2%) | 705 | 54.6 (IQR, 22-60.7) | 27.9 (95% CI, 23.9-35.8) | NR | MFC |
| A phase 3 study comparing DRd vs Rd in subjects with previously untreated MM who are ineligible for high-dose therapy (MAIA-MMY3008)/Janssen R&D16,17 NCT02252172 | DRd: 368 (49.9%) Rd: 369 (50.1%) | 737 | 62.4 (IQR, 57.9-66.8) | 44.8 (95% CI, 40.9-52.4) | 73.7 (95% CI, 69.7-NA) | NGS |
| A phase 3, multicenter, randomized, controlled, open-label study of Velcade VMP compared to daratumumab in combination with VMP (D-VMP), in subjects with previously untreated MM who are ineligible for high-dose therapy (Asia-Pacific region-OCTANS-MMY3011)/Janssen R&D NCT03217812 | D-VMP: 146 (66.4%) VMP: 74 (33.6%) | 220 | 22.9 (IQR, 19-30) | 28.2 (95% CI, 24.4-NR) | 41.6 (95% CI, 41.6-NA) | MFC |
| Study/sponsor . | Treatment, n (%) . | N . | Median follow-up,∗ mo . | Median PFS, mo . | Median OS, mo . | MRD assay† . |
|---|---|---|---|---|---|---|
| TE NDMM | ||||||
| Randomized phase 3 trial for previously untreated MM to evaluate 2 regimens of bortezomib–based induction therapy and lenalidomide consolidation followed by lenalidomide maintenance treatment (MM5)/University Hospital Heidelberg21 https://www.clinicaltrialsregister.eu/ctr-search/trial/2010-019173-16/DE | A1‡: 149 (24.8%) A2‡: 151 (25.1%) B1‡: 150 (25%) B2‡: 151 (25.1%) | 601 | 57.1 (IQR, 44.4-64) | 40.5 (95% CI, 36.5-43.2) | NR | MFC |
| Phase 2, randomized, open-label study comparing D-RVd vs RVd in subjects with NDMM eligible for high-dose chemotherapy and autologous stem cell transplantation (GRIFFIN-MMY2004)/Janssen R&D23 NCT02874742 | D-RVd: 120 (53.8%) RVd: 103 (46.2%) | 223 | 25.4 (IQR, 22.1-28.3) | NR (95% CI, 34.1-NR) | NR | NGS |
| Study of daratumumab in combination with bortezomib (Velcade), VTD in the first line treatment of TE subjects with NDMM (CASSIOPEIA-MMY3006)/Intergroupe Francophone du Myelome24,25 NCT02541383 | D-VTd: 543 (50%) VTd: 542 (50%) | 1085 | 18.2 (IQR, 13.7-24) | NR | NR | NGS |
| TIE NDMM | ||||||
| A randomized, open-label phase 3 study of KMP vs VMP in TIE patients with NDMM (CLARION)/Amgen15 NCT01818752 | KMP: 428 (50.2%) VMP: 425 (49.8%) | 853 | 22.3 (IQR, 19.1-27.6) | 22.2 (95% CI, 21-24.2) | NR | MFC |
| A phase 3, randomized, controlled, open-label study of Velcade VMP compared with daratumumab in combination with VMP (D-VMP) in subjects with previously untreated MM who are ineligible for high-dose therapy (ALCYONE-MMY3007) Janssen R&D26,27 NCT02195479 | D-VMP: 350 (49.6%) VMP: 356 (50.4%) | 706 | 39.9 (IQR, 37.4-42.9) | 24 (95% CI, 21.6-27.4) | NR | NGS |
| A phase 3, randomized, double-blind, multicenter study comparing oral MLN9708 plus Rd vs placebo plus Rd in adult patients with NDMM (TOURMALINE-MM2)/Takeda18 NCT01850524 | IRd: 351 (49.8%) Rd: 354 (50.2%) | 705 | 54.6 (IQR, 22-60.7) | 27.9 (95% CI, 23.9-35.8) | NR | MFC |
| A phase 3 study comparing DRd vs Rd in subjects with previously untreated MM who are ineligible for high-dose therapy (MAIA-MMY3008)/Janssen R&D16,17 NCT02252172 | DRd: 368 (49.9%) Rd: 369 (50.1%) | 737 | 62.4 (IQR, 57.9-66.8) | 44.8 (95% CI, 40.9-52.4) | 73.7 (95% CI, 69.7-NA) | NGS |
| A phase 3, multicenter, randomized, controlled, open-label study of Velcade VMP compared to daratumumab in combination with VMP (D-VMP), in subjects with previously untreated MM who are ineligible for high-dose therapy (Asia-Pacific region-OCTANS-MMY3011)/Janssen R&D NCT03217812 | D-VMP: 146 (66.4%) VMP: 74 (33.6%) | 220 | 22.9 (IQR, 19-30) | 28.2 (95% CI, 24.4-NR) | 41.6 (95% CI, 41.6-NA) | MFC |
DRd, daratumumab, lenalidomide, and dexamethasone; D-RVd, daratumumab, lenalidomide, bortezomib, and dexamethasone; D-VMP, daratumumab, bortezomib, melphalan, and prednisone; D-VTd, daratumumab, bortezomib, thalidomide, and dexamethasone; IRd, isatuximab, lenalidomide, and dexamethasone; Janssen R&D, Janssen Research and Development, LLC; KMP, carfilzomib, melphalan, and prednisone; MFC, multiparameter-flow cytometry; NA, not available; NGS, next-generation sequencing; NR, not reached; Rd, lenalidomide and dexamethasone; RVd, lenalidomide, bortezomib, and dexamethasone; VMP, bortezomib, melphalan, and prednisone.
Follow-up is calculated for the end point of PFS using the reverse Kaplan-Meier estimate.
MFC or NGS.
A1, bortezomib, doxorubicin, dexamethasone, high-dose melphalan, autologous blood stem cell transplantation, and lenalidomide consolidation followed by lenalidomide maintenance therapy for 2 years. B1, bortezomib, doxorubicin, dexamethasone, high-dose melphalan, autologous blood stem cell transplantation, and lenalidomide consolidation followed by lenalidomide maintenance until achievement of CR. A2, bortezomib, cyclophosphamide, dexamethasone, high-dose melphalan, autologous blood stem cell transplantation, and lenalidomide consolidation followed by lenalidomide maintenance therapy for 2 years. B2, bortezomib, cyclophosphamide, and dexamethasone, high-dose melphalan, autologous blood stem cell transplantation, and lenalidomide consolidation followed by lenalidomide maintenance until achievement of CR.