Elotuzumab in combination with pomalidomide, bortezomib, and dexamethasone in relapsed and refractory multiple myeloma.

Abstract

Elotuzumab is an approved monoclonal antibody targeting SLAMF7 on plasma and NK cells that enhances the activity of lenalidomide, pomalidomide, and bortezomib in multiple myeloma (MM). The OPTIMISMM study showed improved outcomes with the combination of pomalidomide, bortezomib, and dexamethasone (PVd) in relapsed/refractory MM. We therefore studied adding elotuzumab to PVd (elo-PVd) in relapsed/refractory MM in a multicenter phase 2 trial. The primary objective was to determine the overall response rate (ORR). Patients with relapsed/refractory disease and ≥1 prior line of treatment (including lenalidomide and a proteasome inhibitor) were eligible. For each 28 day cycle, elotuzumab was weekly for the first 2 cycles and then every other week; pomalidomide was on days 1-21; bortezomib was on days 1, 8, 15; and dexamethasone was weekly. The trial completed accrual in September 2018 with 48 patients receiving treatment. The median age was 64 (range 40-80) and the median number of prior lines was 3 (range 1-9); 25% had high risk FISH. Prior therapies included: pomalidomide (33%), daratumumab (25%), and isatuximab (4%). Best ORR was 56.3% and median PFS was 10 months. In patients with 1 prior line of therapy, ORR was 73.7% and median PFS was 23.4 months. Common grade ≥3 adverse events were neutropenia (33%); infections, any (33%); lung infection (27%); hypophosphatemia (19%); and thrombocytopenia (15%). Elo-PVd is one of the first trials of a quadruplet regimen in relapsed/refractory MM incorporating a monoclonal antibody to show efficacy across diverse prior treatments, including triple class exposed with prior anti-CD38 monoclonal antibody.