Results from clinical trials exploring early treatment in high-risk SMM
| Clinical trial . | Phase . | Treatment . | Follow-up, median (range), mo . | Results . | Safety profile (grade ≥3 AE) . |
|---|---|---|---|---|---|
| QuiRedex (NCT00480363)17 | 3 | Rd vs observation. Induction: 9 × 28-d cycles R 25 mg/d on d 1-21 + Dex 20 mg/d on d 1-4, 12-15. Maintenance: 2 y 28-d cycles with R 10 mg/d on d 1-21. | 73 (66-84) | n = 119. Median TTP: NR (95% CI, 47 mo to NR) vs 23 mo (95% CI, 16-31 mo); HR, 0.24 (95% CI, 0.14-0.41); P < .0001). Median OS: NR in both arms (HR, 0.43; 95% CI, 0.21-0.92; P = .02. | Infection (8%; 1 death), asthenia (6%), neutropenia (5%), and skin rash (3%) |
| NCT0116933721 | 2/3 | R vs observation. R alone at 25 mg d 1-21 every 28 d. | 17 | Preliminary ASH 2013 meeting; n = 44; PR, 33%, SD, 58% | Neutropenia and fatigue (25%) |
| NCT0227939423 | 2 | Elotuzumab + Rd. Elotuzumab 10 mg/kg IV d 1, 8, 15, and 22. Cycles 1 and 2, 10 mg/kg IV d 1 and 15; cycles 3-8, lenalidomide 25 mg d 1-21; cycles 1-24, Dex 40 mg oral d 1, 8, 15, and 22; cycles 1 and 2, 40 mg oral d 1, 8, and 15 in cycles 3-8. | — | n = 31. ORR: 84%; CR: 7%; VGPR: 36%; PR: 42%; clinical benefit rate: 100%. | Hypophosphatemia (30%), neutropenia (14%), infection (12%), anemia (2%), pulmonary embolism (2%), rash (4%), and diarrhea (2%) |
| NCT0144197326 | 2 | Elotuzumab. Cohort 20 mg/kg IV: cycle 1, d 1 and 8; monthly thereafter; cohort 10 mg/kg: cycles 1 and 2 weekly; every 2 wk thereafter. | 28 | n = 31. ORR (90% CI) 10%; 2-y PFS: 69% (52-81%). | 7 (47%) in the 20 mg/kg cohort and 6 (38%) in 10 mg/kg cohort; no grade 3 infusion reactions |
| NCT0148427524 | 2 | Siltuximab vs placebo.15 mg/kg siltuximab or placebo 1-h IV infusion every 4 wk until disease progression to MM. | 29.2 | n = 85. 1-y PFS: 84.5% (95% CI, 68.6-92.8) vs 74.4% (95% CI, 57.3-85.5). | Infections and renal and urinary disorders (1 patient in the siltuximab group and 3 patients in the placebo group); 7 patients died (3 in the siltuximab group [pneumonia (n = 1)] and unknown (n = 2)]) |
| CENTAURUS (NCT02316106)25 | 2 | Daratumumab. 16 mg/kg IV in 8-wk cycles. Long: every wk in cycle 1, every other wk in cycles 2 and 3, every 4 wk in cycles 4-7, and every 8 wk up to cycle 20. Intermediate: every wk in cycle 1 and every 8 wk up to cycle 20. Short: every wk for 1 cycle. | 15.8 (0.0-23.9) | n = 41 in each arm; ORR: 56%/54%/38%; 12-mo PFS, 95%/88%/81% | Infection (<5% in all arms) |
| NCT0157248022 | 2 | Carfilzomib + Rd. Eight 28-d cycles of carfilzomib 20/36 mg/m2 on d 1, 2, 8, 9, 15, and 16; lenalidomide 25 mg on d 1-21; and Dex 20/10 mg (cycles 1-4/5-8) on days 1, 2, 8, 9, 15, 16, 22, and 23 + 2-y R maintenance. | 15.9 | n = 12; CR, 100%; MRD (flow), 92% | Skin (33%), neutropenia (17%), anemia (17%), infection (8%), and cardiac (8%) |
| CESAR (NCT02415413)19 | 2 | Induction: KRd × 6 cycles (carfilzomib IV 20/36 mg/m2 d 1, 2, 8, 9, 15, and 16/lenalidomide 25 mg d 1-21/Dex 40 mg d 1, 8, 15, and 22). ASCT: consolidation, KRd × 2 cycles; maintenance, Rd × 2 cycles. | 17 (5-36) | n = 90; efficacy after ASCT (+100); ORR, 100%; ≥CR, 63%; VGPR, 23%; MRD-ve rate (flow), 55% | Neutropenia (6%), thrombocytopenia (11%), infections (18%), and skin rash (9%) |
| ASCENT (NCT03289299) | 2 | Induction: 6 cycles, KRd + daratumumab. Consolidation: 6 cycles, KRd + daratumumab vs ASCT maintenance: 12 cycles, R + daratumumab. | — | Ongoing | Not yet available |
| Clinical trial . | Phase . | Treatment . | Follow-up, median (range), mo . | Results . | Safety profile (grade ≥3 AE) . |
|---|---|---|---|---|---|
| QuiRedex (NCT00480363)17 | 3 | Rd vs observation. Induction: 9 × 28-d cycles R 25 mg/d on d 1-21 + Dex 20 mg/d on d 1-4, 12-15. Maintenance: 2 y 28-d cycles with R 10 mg/d on d 1-21. | 73 (66-84) | n = 119. Median TTP: NR (95% CI, 47 mo to NR) vs 23 mo (95% CI, 16-31 mo); HR, 0.24 (95% CI, 0.14-0.41); P < .0001). Median OS: NR in both arms (HR, 0.43; 95% CI, 0.21-0.92; P = .02. | Infection (8%; 1 death), asthenia (6%), neutropenia (5%), and skin rash (3%) |
| NCT0116933721 | 2/3 | R vs observation. R alone at 25 mg d 1-21 every 28 d. | 17 | Preliminary ASH 2013 meeting; n = 44; PR, 33%, SD, 58% | Neutropenia and fatigue (25%) |
| NCT0227939423 | 2 | Elotuzumab + Rd. Elotuzumab 10 mg/kg IV d 1, 8, 15, and 22. Cycles 1 and 2, 10 mg/kg IV d 1 and 15; cycles 3-8, lenalidomide 25 mg d 1-21; cycles 1-24, Dex 40 mg oral d 1, 8, 15, and 22; cycles 1 and 2, 40 mg oral d 1, 8, and 15 in cycles 3-8. | — | n = 31. ORR: 84%; CR: 7%; VGPR: 36%; PR: 42%; clinical benefit rate: 100%. | Hypophosphatemia (30%), neutropenia (14%), infection (12%), anemia (2%), pulmonary embolism (2%), rash (4%), and diarrhea (2%) |
| NCT0144197326 | 2 | Elotuzumab. Cohort 20 mg/kg IV: cycle 1, d 1 and 8; monthly thereafter; cohort 10 mg/kg: cycles 1 and 2 weekly; every 2 wk thereafter. | 28 | n = 31. ORR (90% CI) 10%; 2-y PFS: 69% (52-81%). | 7 (47%) in the 20 mg/kg cohort and 6 (38%) in 10 mg/kg cohort; no grade 3 infusion reactions |
| NCT0148427524 | 2 | Siltuximab vs placebo.15 mg/kg siltuximab or placebo 1-h IV infusion every 4 wk until disease progression to MM. | 29.2 | n = 85. 1-y PFS: 84.5% (95% CI, 68.6-92.8) vs 74.4% (95% CI, 57.3-85.5). | Infections and renal and urinary disorders (1 patient in the siltuximab group and 3 patients in the placebo group); 7 patients died (3 in the siltuximab group [pneumonia (n = 1)] and unknown (n = 2)]) |
| CENTAURUS (NCT02316106)25 | 2 | Daratumumab. 16 mg/kg IV in 8-wk cycles. Long: every wk in cycle 1, every other wk in cycles 2 and 3, every 4 wk in cycles 4-7, and every 8 wk up to cycle 20. Intermediate: every wk in cycle 1 and every 8 wk up to cycle 20. Short: every wk for 1 cycle. | 15.8 (0.0-23.9) | n = 41 in each arm; ORR: 56%/54%/38%; 12-mo PFS, 95%/88%/81% | Infection (<5% in all arms) |
| NCT0157248022 | 2 | Carfilzomib + Rd. Eight 28-d cycles of carfilzomib 20/36 mg/m2 on d 1, 2, 8, 9, 15, and 16; lenalidomide 25 mg on d 1-21; and Dex 20/10 mg (cycles 1-4/5-8) on days 1, 2, 8, 9, 15, 16, 22, and 23 + 2-y R maintenance. | 15.9 | n = 12; CR, 100%; MRD (flow), 92% | Skin (33%), neutropenia (17%), anemia (17%), infection (8%), and cardiac (8%) |
| CESAR (NCT02415413)19 | 2 | Induction: KRd × 6 cycles (carfilzomib IV 20/36 mg/m2 d 1, 2, 8, 9, 15, and 16/lenalidomide 25 mg d 1-21/Dex 40 mg d 1, 8, 15, and 22). ASCT: consolidation, KRd × 2 cycles; maintenance, Rd × 2 cycles. | 17 (5-36) | n = 90; efficacy after ASCT (+100); ORR, 100%; ≥CR, 63%; VGPR, 23%; MRD-ve rate (flow), 55% | Neutropenia (6%), thrombocytopenia (11%), infections (18%), and skin rash (9%) |
| ASCENT (NCT03289299) | 2 | Induction: 6 cycles, KRd + daratumumab. Consolidation: 6 cycles, KRd + daratumumab vs ASCT maintenance: 12 cycles, R + daratumumab. | — | Ongoing | Not yet available |
AE, adverse event; ASCT, autologous stem cell transplantation; ASH, American Society of Hematology; CR, complete response; Dex, dexamethasone; flow, flow cytometry; MRD, minimal residual disease; MRD-ve, minimal residual disease negative; ORR, overall response rate; OS, overall survival; PFS, progression-free survival; PR, partial response; R, lenalidomide; SD, stable disease; VGPR, very good partial response.