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

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, 87%), cyclophosphamide (n=20, 29%), carfilzomib (n=14, 21%), and autologous stem cell transplantation (n=38, 56%). At analysis, pts had received a median of 9 cycles of EPd and 13 (19%) were still on treatment. The most common reasons for discontinuation were disease progression (n=26, 38%) and maximum clinical benefit (n=10, 15%). Median PFS was 11.1 mo (Figure) and ORR was 51%. Overall, 9 pts (13%) achieved very good partial response or better, 26 (38%) achieved partial response, and 12 (18%) achieved minimal response. Median (95% CI) duration of response was 16.7 (11.3, not estimable [NE]) mo. Median time to first response was 1 mo, and to best response was 2.8 mo. Median (95% CI) OS was 22.4 (21.8, NE) mo. Pts with ≥2 prior therapies had a median (95% CI) PFS of 11.1 (5.6, 15.0) mo and an ORR of 46%. The most frequent all-cause non-hematologic adverse events (AEs) were fatigue (n=37, 54%), diarrhea (n=23, 34%), and upper respiratory tract infection (n=23, 34%); all-cause infections were reported in 47 pts (69%). No second primary malignancies were reported. The most common all-cause hematologic AE was neutropenia, reported in 24 pts (35%) and grade 3-4 in 11 (16%). Anemia was reported in 15 pts (22%) and was grade 3-4 in 4 (6%). Infusion reactions were reported in 5 pts (7%), all grade 1-2. In total, 7 pts (10%) experienced grade 5 AEs, 1 of which (pulmonary sepsis) was considered related to treatment. Overall, 11 pts (16%) experienced AEs leading to discontinuation.

Conclusions: EPd was associated with a median PFS of 11.1 mo and ORR of 51% in pts with RRMM. Safety was consistent with prior reports of elotuzumab and pom, with no new safety signals. These data, coupled with findings from the randomized ELOQUENT-3 study, support EPd as a new, effective treatment option for pts with RRMM.

Study support: BMS. Medical writing: Adam Gill, Caudex, funded by BMS

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