Selected studies with elotuzumab and CD38-targeting antibodies as single agent in relapsed/refractory MM
| Study . | Type of study . | Regimen . | Schedule . | N . | Prior treatment . | Response . | TTE . | Key toxicities . |
|---|---|---|---|---|---|---|---|---|
| Zonder et al29 | Phase 1 | Elotuzumab | MTD not reached; highest dose-level: elotuzumab 20 mg/kg iv; administered once every 2 weeks for 8 weeks; patients without PD or relapse at week 8 had the option to receive a second 8-week treatment course | 34 | Median: 4.5 Range: 2-10 Thal: 79.4% Len: 82.4% Bort: 82.4% | ≥PR: 0% SD: 26.5% | Not reported | IRR before institution of infusion prophylaxis: 52% |
| Lokhorst et al30 (GEN501) | Phase 1/2 | Daratumumab | MTD not reached; highest dose level: daratumumab 24 mg/kg iv; in part 2, daratumumab 8 or 16 mg/kg iv was administered once-weekly for 8 times (schedules D and E: 3-week wash out period after infusion 1), and then twice-monthly for 14-16 weeks, followed by monthly infusions until PD/unacceptable toxicity | Phase 2 with daratumumab 16 mg/kg: 42 | Phase 2 with daratumumab 16 mg/kg; Median: 4 Range: 2-12 Thal-refractory: 29% Len-refractory: 74% Bort-refractory: 71% Carf-refractory: 17% Pom-refractory: 36% | Phase 2 with daratumumab 16 mg/kg; ≥PR: 36% VGPR: 5% CR: 5% | Phase 2 with daratumumab 16 mg/kg; Median PFS: 5.6 months 1-year OS: 77% | Phase 2 with daratumumab 16 mg/kg; IRR: 74%; mostly grade 1/2 (grade 3 in 2%) |
| Lonial et al31 (Sirius) | Phase 2 | Daratumumab | Initially daratumumab 8 or 16 mg/kg; 16 mg/kg was established as the recommended dose for further study. Daratumumab 16 mg/kg was given weekly for 8 weeks, every 2 weeks for 16 weeks, followed by monthly infusions | Daratumumab 16 mg/kg: 106 | Daratumumab 16 mg/kg; Median: 5 Range: 2-14 Thal: 44% Len-refractory: 88% Bort-refractory: 90% Carf-refractory: 48% Pom-refractory: 63% | Daratumumab 16 mg/kg; ≥PR: 29% VGPR: 9% CR: 3% | Daratumumab 16 mg/kg; Median PFS: 3.7 months 1-year OS: 65% | Daratumumab 16 mg/kg; IRR: 43%; mostly grade 1/2 (grade 3 in 5%) |
| Martin et al32,33 | Phase 1 | Isatuximab | MTD not reached; highest dose-level: isatuximab 20 mg/kg iv; isatuximab was administered every 2 weeks or weekly | Total patients with CD38+ hematological malignancies: 39MM patients: 35 | MM patients; Median: 6 Range: 2-14 IMiD and PI: 97% Carf and/or pom: 57% | MM patients treated with isatuximab ≥ 10 mg/kg (n=18); ≥PR: 33% CR: 11% | MM patients; Not reported | MM patients treated with isatuximab ≥10 mg/kg; IRR: 43% (mostly grade 1/2) |
| Raab et al34 | Phase 1/2a | MOR202 | MTD not reached; highest dose-level: MOR202 16 mg/kg iv; MOR202 was administered every 2 weeks or weekly | 45 | Median: 4 Range: not reported Thal: 36% Len: 98% Bort: 100% Carf: 7% Pom: 16% | MOR202 ≥ 1.5 mg/kg (n = 24); ≥PR: 8.3% VGPR: 4.2% | Not reported | IRR: 40% in patients without dexamethasone as premedication, mostly grade 1/2 (grade 3 in 3%) IRR: 10% in patients with dexamethasone as premedication |
| Study . | Type of study . | Regimen . | Schedule . | N . | Prior treatment . | Response . | TTE . | Key toxicities . |
|---|---|---|---|---|---|---|---|---|
| Zonder et al29 | Phase 1 | Elotuzumab | MTD not reached; highest dose-level: elotuzumab 20 mg/kg iv; administered once every 2 weeks for 8 weeks; patients without PD or relapse at week 8 had the option to receive a second 8-week treatment course | 34 | Median: 4.5 Range: 2-10 Thal: 79.4% Len: 82.4% Bort: 82.4% | ≥PR: 0% SD: 26.5% | Not reported | IRR before institution of infusion prophylaxis: 52% |
| Lokhorst et al30 (GEN501) | Phase 1/2 | Daratumumab | MTD not reached; highest dose level: daratumumab 24 mg/kg iv; in part 2, daratumumab 8 or 16 mg/kg iv was administered once-weekly for 8 times (schedules D and E: 3-week wash out period after infusion 1), and then twice-monthly for 14-16 weeks, followed by monthly infusions until PD/unacceptable toxicity | Phase 2 with daratumumab 16 mg/kg: 42 | Phase 2 with daratumumab 16 mg/kg; Median: 4 Range: 2-12 Thal-refractory: 29% Len-refractory: 74% Bort-refractory: 71% Carf-refractory: 17% Pom-refractory: 36% | Phase 2 with daratumumab 16 mg/kg; ≥PR: 36% VGPR: 5% CR: 5% | Phase 2 with daratumumab 16 mg/kg; Median PFS: 5.6 months 1-year OS: 77% | Phase 2 with daratumumab 16 mg/kg; IRR: 74%; mostly grade 1/2 (grade 3 in 2%) |
| Lonial et al31 (Sirius) | Phase 2 | Daratumumab | Initially daratumumab 8 or 16 mg/kg; 16 mg/kg was established as the recommended dose for further study. Daratumumab 16 mg/kg was given weekly for 8 weeks, every 2 weeks for 16 weeks, followed by monthly infusions | Daratumumab 16 mg/kg: 106 | Daratumumab 16 mg/kg; Median: 5 Range: 2-14 Thal: 44% Len-refractory: 88% Bort-refractory: 90% Carf-refractory: 48% Pom-refractory: 63% | Daratumumab 16 mg/kg; ≥PR: 29% VGPR: 9% CR: 3% | Daratumumab 16 mg/kg; Median PFS: 3.7 months 1-year OS: 65% | Daratumumab 16 mg/kg; IRR: 43%; mostly grade 1/2 (grade 3 in 5%) |
| Martin et al32,33 | Phase 1 | Isatuximab | MTD not reached; highest dose-level: isatuximab 20 mg/kg iv; isatuximab was administered every 2 weeks or weekly | Total patients with CD38+ hematological malignancies: 39MM patients: 35 | MM patients; Median: 6 Range: 2-14 IMiD and PI: 97% Carf and/or pom: 57% | MM patients treated with isatuximab ≥ 10 mg/kg (n=18); ≥PR: 33% CR: 11% | MM patients; Not reported | MM patients treated with isatuximab ≥10 mg/kg; IRR: 43% (mostly grade 1/2) |
| Raab et al34 | Phase 1/2a | MOR202 | MTD not reached; highest dose-level: MOR202 16 mg/kg iv; MOR202 was administered every 2 weeks or weekly | 45 | Median: 4 Range: not reported Thal: 36% Len: 98% Bort: 100% Carf: 7% Pom: 16% | MOR202 ≥ 1.5 mg/kg (n = 24); ≥PR: 8.3% VGPR: 4.2% | Not reported | IRR: 40% in patients without dexamethasone as premedication, mostly grade 1/2 (grade 3 in 3%) IRR: 10% in patients with dexamethasone as premedication |
bort, bortezomib; carf, carfilzomib; CR, complete response; dex, dexamethasone; IRR, infusion-related reaction; len, lenalidomide; PD, progressive disease; PFS, progression-free survival; PI, proteasome inhibitor; pom, pomalidomide; PR, partial response; thal, thalidomide; TTE, time to events; VGPR, very good partial response.