Table 1.

Clinical studies with E alone or in combination with established MM therapies

Study/Phase	Patient population and treatment	Previous treatments	Key efficacy parameters	Key safety parameters	References
E single-agent therapy
NCT00425347 (Study 1701) Phase I	35 pts with RRMM E dose: 0.5–20 mg/kg  Enrolled: 35  Treated: 34	m: 4.5 (range 2–10) T: 79.4% L: 82.4% B: 82.4%	ORR: 0% SD: 26.5%	2 DLTs (increased serum creatinine, hypersensitivity) MTD not reached Infusion reactions: 52% (without premedication) Infections: 29.4% Most common related AEs: chills, pyrexia, flushing	28
E/L combination therapy
NCT00742560 (Study 1703) Phase I/II	102 pts with RRMM Phase I part: E–L/d E dose: 5–20 mg/kg  Enrolled: 29  Treated: 28 Phase II part: E–L/d E dose: 10 versus 20 mg/kg  Enrolled: 73  Treated: 73	m: na (range: 1–3) T: 62% L: na B: 60%	Phase I:  ORR: 82%  mPFS: 29 months Phase II:  ORR: 84%  mPFS: 28.6 months	No DLTs, MTD not reached Phase II: Infusion reactions: 11% Most frequent AEs: diarrhea, muscle spasms, and fatigue Most frequent grade 3/4 AEs: lymphopenia (21%), neutropenia (19%)	33,38
NCT01239797 (CA204-004; ELOQUENT-2) Phase III	646 pts with RRMM E dose: 10 mg/kg E–L/d: Enrolled: 321  Treated: 318 L/d: Enrolled: 325  Treated: 317	m: 2 (range: 1–4) T: 48% L: 6% B: 70%	ORR: 78.5% versus 66.5% mPFS: 19.4 versus 14.9 months (HR: 0.70) Prelim. mOS: 43.7 versus 39.6 months (HR: 0.77)	Infusion reactions: 10% Infections: 81% versus 74% (198 vs 192 events/100 patient-years) Most frequent grade 3/4 AEs: lymphopenia (77% vs 49%) neutropenia (34% vs 44%)	39,46
NCT01241292 (CA204-005) Japanese pts	Six Japanese pts with RRMM Treatment: E–L/d E dose: 10 or 20 mg/kg  Enrolled/treated: 6	na	ORR: 83% (5 of 6 pts)	Most frequent AEs: leukopenia, lymphopenia, neutropenia, dysgeusia, constipation, pyrexia, nasopharyngitis, and rash	(not published yet) For results, see www.ClinicalTrials.gov
NCT01393964 (CA204-007) Phase Ib	26 MM pts with different levels of renal impairment Treatment: E–L/d E dose: 10 mg/kg  Enrolled: 26  Treated: 26	m: 2 (range: 1–7) T: 42% L: 35% B: 81%	PK: E serum levels comparable across all treatment groups ORR: 75% in NRF, 67% in SRI, 56% in ESRD	Infusion reactions: 12% AEs comparable across all treatment groups Most common AEs: fatigue, diarrhea, back pain, constipation, and anemia Dose adjustments for renal dysfunction were not required	37
E/B combination therapy
NCT00726869 (Study 1702) Phase I	28 pts with RRMM Treatment: E–B E dose: 2.5–20 mg/kg  Enrolled: 28  Treated: 28	m: 2 (range: 1–3) T: na L: 46% B: 39%	ORR: 48%, including two (67%) of three pts refractory to B mTTP: 9.5 months	No DLTs, MTD not reached Infusion reactions: 71% Hypersensitivity: 7% (grade 3/4: 4%) Most frequent AEs: fatigue, anemia, diarrhea, thrombocytopenia Most frequent grade 3/4 AEs: lymphopenia (25%), fatigue (14%)	32
NCT01478048 (CA204-009) Phase II	152 pts with RRMM E dose: 10 mg/kg E–B/d  Enrolled: 77  Treated: 75 B/d:  Enrolled: 75  Treated: 75	m: na (range: 1–3) T: na L: na B: 51%	ORR: 66% versus 63% mPFS: 9.7 versus 6.9 months (HR: 0.72)	Infusion reactions: 5% Most frequent AEs: infections (67% vs 53%), diarrhea (44% vs 33%) Most frequent grade 3/4 AEs: infections (21% vs 13%), thrombocytopenia (9% vs 17%), peripheral neuropathy (9% vs 12%)	53,54

Abbreviations: AE, adverse event; B, bortezomib; d, dexamethasone; DLT, dose-limiting toxicity; E, elotuzumab; ESRD, end-stage renal disease; HR, hazard ratio; L, lenalidomide; m, median; mPFS, median progression-free survival; MTD, maximum tolerated dose; mTTP, median time to progression; na, not available; NRF, normal renal function; ORR, objective response rate; OS, overall survival; PFS, progression-free survival; PK, pharmacokinetic; pts, patients; RRMM, relapsed/refractory multiple myeloma; SD, stable disease; SRI, severe renal impairment; T, thalidomide; TTP, time to progression.