A randomized phase II study of elotuzumab with lenalidomide and low-dose dexamethasone in patients with relapsed/refractory multiple myeloma.

8020 Background: Elotuzumab (Elo) is a humanized monoclonal IgG1 antibody targeting CS1, a cell surface glycoprotein. CS1 is highly expressed on >95% of multiple myeloma (MM) cells, with lower expression on natural killer cells and little to no expression on normal tissues. A phase 1 trial of Elo plus lenalidomide and low-dose dexamethasone (Elo/Len/Dex) demonstrated an 82% objective response rate (ORR) in patients (pts) with relapsed/refractory (RR) MM (Lonial et al. J Clin Oncol, in press). Methods: In this phase 2 study, previously treated pts with MM were randomized to Elo 10 or 20 mg/kg IV (days 1, 8, 15, and 22 every 28-days in first 2 cycles and days 1 and 15 of subsequent cycles), Len 25 mg PO (days 1-21) and Dex 40 mg PO weekly. Prophylaxis for infusion-related reactions (IRs) was administered prior to each Elo infusion. Treatment continued until disease progression or unacceptable toxicity. The primary objective was to assess efficacy (ORR ≥partial response [PR]) according to IMWG criteria. Results: Among73 pts (median age 63 years; range, 39-82), 55% had received ≥2 prior therapies, 60% had received prior bortezomib, and 62% prior thalidomide. ORR was 82% for all pts including 48% ≥ very good PR (VGPR). The ORRs were 92% in the 10 mg/kg group (n=36) and 73% in the 20 mg/kg group (n=37). Median time to best response was 2.2 months (range, 0.7-17.5). After a median follow-up of 14.1 months, median progression-free survival (PFS) has not been reached, with PFS rates of 75% (10 mg/kg) and 65% (20 mg/kg). Elo/Len/Dex also showed encouraging activity in pts with high-risk cytogenetics (ORR 80%) and/or Stage 2-3 MM (ORR 81%). The most common grade 3/4 toxicities were neutropenia (16%), lymphopenia (16%), and thrombocytopenia (16%). Investigator-designated IRs were reported in 12% of pts (all grades); 1 pt (1.4%) had grade 3 IR (rash). Conclusions: Elo/Len/Dex was generally well tolerated and resulted in a high ORR, and PFS not reached after 14.1 months of median follow-up in pts with RR MM. Updated results will be presented at the meeting. Two phase 3 trials of 10 mg/kg Elo/Len/Dex are ongoing in newly diagnosed MM (ELOQUENT1; CA204-006; NCT01335399) and RR MM (ELOQUENT2; CA204-004; NCT01239797).