Elotuzumab Plus Pomalidomide and Dexamethasone for Relapsed/Refractory Multiple Myeloma: Initial Data from a Phase 2, Non-Comparative Study

• Published in: Blood 2018-11, Vol.132 (Supplement 1), p.1991-1991
• Main Authors: Jagannath, Sundar, Berdeja, Jesus G., Rifkin, Robert M, Cole, Craig E., Thompson, Michael Alan, Vij, Ravi, Popa-McKiver, Mihaela, Saleem, Rao, Sy, Oumar, Bensinger, William
• Format: Article
• Language: English
• ISSN: 0006-4971; 1528-0020
• DOI: 10.1182/blood-2018-99-112077

Introduction: Despite therapeutic advances, most patients (pts) with multiple myeloma (MM) eventually develop relapsed/refractory (RR) disease, and observational studies of pts refractory to immunomodulatory drugs and proteasome inhibitors have demonstrated a median overall survival (OS) of 13 mo (Kumar et al, Leukemia 2017;31:2443-8). Elotuzumab, an immunostimulatory monoclonal antibody targeted to SLAMF7, directly activates natural killer cells and mediates the killing of MM cells through antibody-dependent cellular cytotoxicity and antibody-dependent cellular phagocytosis. Elotuzumab, combined with lenalidomide (len) and dexamethasone (dex), is indicated in the USA and EU for RRMM in pts who have received ≥1 prior therapy. Pomalidomide (pom), a 2nd-generation immunomodulatory drug, appears to synergize with elotuzumab. The phase 2, randomized, international, exploratory ELOQUENT-3 study (NCT02654132) assessed elotuzumab combined with pom and dex (EPd) vs pom and dex (Pd); after a minimum follow-up of 9 mo, median progression-free survival (PFS) with EPd was 10.3 vs 4.7 mo with Pd (hazard ratio=0.54) and the overall response rate (ORR) was 53% vs 26% (Dimopoulos et al, EHA 2018 [LB2606]). In this supportive study, with a minimum follow-up of 16 mo, we present initial efficacy and safety data for EPd in pts with relapsed and/or refractory MM. Methods: This phase 2, multicenter, non-comparative study (NCT02612779) enrolled pts ≥18 y of age with MM who were relapsed, refractory, or intolerant to len (received for ≥2 consecutive cycles), 1-2 prior therapies, disease progression during or after their last therapy, and with an Eastern Cooperative Oncology Group performance status of ≤2. Prior pom was not permitted. Pts received elotuzumab 10 mg/kg IV weekly for the first two 28-d cycles and 20 mg/kg IV every 4 wk thereafter. Pom 4 mg orally was given on Days 1-21 of each cycle and dex 40 or 20 mg oral equivalent was given weekly for pts ≤75 or >75 y of age, respectively. Primary endpoint was PFS; additional endpoints included OS, ORR, and safety. Results: At database lock (Apr 4, 2018), 68 pts had received EPd. At baseline, median age was 67 y, 35 pts (51%) were male, and 21 (31%) had International Staging System stage II-III disease. Median (range) prior number of therapies was 2 (1-5) and 34 pts (50%) were relapsed and refractory to their most recent therapy; 6 pts had received ≥3 prior therapies. Prior therapies included len (n=68, 100%), bortezomib (n=59,