Table 2 Selected studies with elotuzumab... | American Society of Hematology

Table 2

Selected studies with elotuzumab and CD38-targeting antibodies in combination with other agents in relapsed/refractory MM

Study	Type of study	Regimen	Schedule	N	Prior treatment	Response	TTE	Key toxicities
Lonial et al⁴²	Phase 3	Elotuzumab plus len-dex Len-dex	Elotuzumab: 10 mg/kg iv on days 1, 8, 15, and 22 during first 2 cycles and then on days 1 and 15 starting with third cycle Len: 25 mg by mouth on days 1-21 of 28-day cycle Dex: once weekly, on elotuzumab days 8 mg iv and 28 mg by mouth, on other days 40 mg by mouth Len: 25 mg on days 1-21 of 28-day cycle Dex: 40 mg once weekly	646	Median: 2 Range: 1-4 Thal: 48% Len (not refractory): 6% Bort: 70%	≥PR: 79% VGPR: 28% CR: 4% ≥PR: 66% VGPR: 21% CR: 7%	Median PFS: 19.4 months Median PFS: 14.9 months	Grade 3/4 lymphopenia: 77% Herpes zoster: 4.1 per 100 patient-years IRR: 10% (mostly grade 1/2) Grade 3/4 lymphopenia: 49% Herpes zoster: 2.2 per 100 patient-years
Jakubowiak et al⁴³	Randomized phase 2	Elotuzumab plus bort-dex Bort-dex	Elotuzumab: 10 mg/kg iv on days 1, 8, and 15 during cycles 1-2; on days 1 and 11 during cycles 3-8; cycle 9+: on days 1 and 15 Bort: 1.3 mg/m² iv or sc on days 1, 4, 8, and 11 of 21-day cycle, during cycles 1-8; cycle 9+: on days 1, 8, and 15 of 28-d cycle Dex: 20 mg by mouth (8 mg iv and 8 mg by mouth on elotuzumab dosing days) Bort: 1.3 mg/m² iv or sc on days 1, 4, 8, and 11 of 21-day cycle, during cycles 1-8; cycle 9+: on days 1, 8, and 15 of 28-day cycle Dex: 20 mg by mouth	152	Median: 1 Range: 1-3 Prior IMiD: 74% Prior PI (not refractory): 52%	≥PR: 65% VGPR: 30% CR: 4% ≥PR: 63% VGPR: 23% CR: 4%	Median PFS: 9.7 months 1-year OS: 85% Median PFS: 6.9 months 1-year OS: 74%	IRR in elotuzumab group: 7% (all grade 1/2); no additional events in elotuzumab group compared with control group
Plesner et al^44,45 (GEN503)	Phase 1/2	Daratumumab plus len-dex	MTD not reached; highest dose-level: Daratumumab 16 mg/kg iv weekly during the first 2 cycles, every other week during cycles 3-6, and monthly in cycle 7 and beyond until PD or unacceptable toxicity Len: 25 mg by mouth on days 1-21 of 28-day cycle Dex: 40 mg weekly	Phase 2 with daratumumab 16 mg/kg: 32	Phase 2 with daratumumab 16 mg/kg; Median: 2 Range: 1-3 Thal: not reported Len (not refractory): 34% Bort: not reported	Phase 2 with daratumumab 16 mg/kg; ≥PR: 88% VGPR: 28% CR: 25%	Phase 2 with daratumumab 16 mg/kg Not reported	Phase 2 with daratumumab 16 mg/kg; IRR: 56%, mostly grade 1/2 (grade 3 in 6%)
Chari et al⁴⁶	Phase 1b	Daratumumab plus pom-dex	Daratumumab 16 mg/kg iv weekly during the first 2 cycles, every other week during cycles 3-6, and monthly in cycle 7 and beyond until PD or unacceptable toxicity Pom: 4 mg by mouth on days 1-21 of 28-day cycle Dex: 40 mg weekly (20 mg for patients >75 years of age)	77	Median: 3.5 Range: 2-10 Thal-refractory: not reported: Len-refractory: 88% Bort-refractory: 65% Carf-refractory: 30% PI and IMID-refractory: 65%	53 patients with > 1 post-baseline assessment; ≥ PR: 59% VGPR: 23% CR: 8% Double-refractory patients (n=40); ≥ PR: 58%	Not reported	IRR: 61%; little additional toxicity when daratumumab was added to pom-dex
Martin et al⁴⁷	Phase 1b	Isatuximab plus len-dex	MTD not reached; highest dose-level: Isatuximab 10 mg/kg iv on days 1 and 15 of each 28-day cycle Len: 25 mg by mouth on days 1-21 of 28-d cycle Dex: 40 mg weekly	Isatuximab 10 mg/kg: 24Whole group: 31	Isatuximab 10 mg/kg; Median: 4 Range: 1-9 Thal-refractory: NA Len-refractory: ∼80% Bort-refractory: ∼60% Carf-refractory: ∼50% Pom-refractory: ∼30%	Isatuximab 10 mg/kg; ≥PR: 63% VGPR: 29% CR: 8%	Whole group Median PFS: 6.2 months	Whole group; IRR: 39% (grade 3 in 6%)

Study	Type of study	Regimen	Schedule	N	Prior treatment	Response	TTE	Key toxicities
Lonial et al⁴²	Phase 3	Elotuzumab plus len-dex Len-dex	Elotuzumab: 10 mg/kg iv on days 1, 8, 15, and 22 during first 2 cycles and then on days 1 and 15 starting with third cycle Len: 25 mg by mouth on days 1-21 of 28-day cycle Dex: once weekly, on elotuzumab days 8 mg iv and 28 mg by mouth, on other days 40 mg by mouth Len: 25 mg on days 1-21 of 28-day cycle Dex: 40 mg once weekly	646	Median: 2 Range: 1-4 Thal: 48% Len (not refractory): 6% Bort: 70%	≥PR: 79% VGPR: 28% CR: 4% ≥PR: 66% VGPR: 21% CR: 7%	Median PFS: 19.4 months Median PFS: 14.9 months	Grade 3/4 lymphopenia: 77% Herpes zoster: 4.1 per 100 patient-years IRR: 10% (mostly grade 1/2) Grade 3/4 lymphopenia: 49% Herpes zoster: 2.2 per 100 patient-years
Jakubowiak et al⁴³	Randomized phase 2	Elotuzumab plus bort-dex Bort-dex	Elotuzumab: 10 mg/kg iv on days 1, 8, and 15 during cycles 1-2; on days 1 and 11 during cycles 3-8; cycle 9+: on days 1 and 15 Bort: 1.3 mg/m² iv or sc on days 1, 4, 8, and 11 of 21-day cycle, during cycles 1-8; cycle 9+: on days 1, 8, and 15 of 28-d cycle Dex: 20 mg by mouth (8 mg iv and 8 mg by mouth on elotuzumab dosing days) Bort: 1.3 mg/m² iv or sc on days 1, 4, 8, and 11 of 21-day cycle, during cycles 1-8; cycle 9+: on days 1, 8, and 15 of 28-day cycle Dex: 20 mg by mouth	152	Median: 1 Range: 1-3 Prior IMiD: 74% Prior PI (not refractory): 52%	≥PR: 65% VGPR: 30% CR: 4% ≥PR: 63% VGPR: 23% CR: 4%	Median PFS: 9.7 months 1-year OS: 85% Median PFS: 6.9 months 1-year OS: 74%	IRR in elotuzumab group: 7% (all grade 1/2); no additional events in elotuzumab group compared with control group
Plesner et al^44,45 (GEN503)	Phase 1/2	Daratumumab plus len-dex	MTD not reached; highest dose-level: Daratumumab 16 mg/kg iv weekly during the first 2 cycles, every other week during cycles 3-6, and monthly in cycle 7 and beyond until PD or unacceptable toxicity Len: 25 mg by mouth on days 1-21 of 28-day cycle Dex: 40 mg weekly	Phase 2 with daratumumab 16 mg/kg: 32	Phase 2 with daratumumab 16 mg/kg; Median: 2 Range: 1-3 Thal: not reported Len (not refractory): 34% Bort: not reported	Phase 2 with daratumumab 16 mg/kg; ≥PR: 88% VGPR: 28% CR: 25%	Phase 2 with daratumumab 16 mg/kg Not reported	Phase 2 with daratumumab 16 mg/kg; IRR: 56%, mostly grade 1/2 (grade 3 in 6%)
Chari et al⁴⁶	Phase 1b	Daratumumab plus pom-dex	Daratumumab 16 mg/kg iv weekly during the first 2 cycles, every other week during cycles 3-6, and monthly in cycle 7 and beyond until PD or unacceptable toxicity Pom: 4 mg by mouth on days 1-21 of 28-day cycle Dex: 40 mg weekly (20 mg for patients >75 years of age)	77	Median: 3.5 Range: 2-10 Thal-refractory: not reported: Len-refractory: 88% Bort-refractory: 65% Carf-refractory: 30% PI and IMID-refractory: 65%	53 patients with > 1 post-baseline assessment; ≥ PR: 59% VGPR: 23% CR: 8% Double-refractory patients (n=40); ≥ PR: 58%	Not reported	IRR: 61%; little additional toxicity when daratumumab was added to pom-dex
Martin et al⁴⁷	Phase 1b	Isatuximab plus len-dex	MTD not reached; highest dose-level: Isatuximab 10 mg/kg iv on days 1 and 15 of each 28-day cycle Len: 25 mg by mouth on days 1-21 of 28-d cycle Dex: 40 mg weekly	Isatuximab 10 mg/kg: 24Whole group: 31	Isatuximab 10 mg/kg; Median: 4 Range: 1-9 Thal-refractory: NA Len-refractory: ∼80% Bort-refractory: ∼60% Carf-refractory: ∼50% Pom-refractory: ∼30%	Isatuximab 10 mg/kg; ≥PR: 63% VGPR: 29% CR: 8%	Whole group Median PFS: 6.2 months	Whole group; IRR: 39% (grade 3 in 6%)