An open-label, single arm, phase IIa study of bortezomib, lenalidomide, dexamethasone, and elotuzumab in newly diagnosed multiple myeloma.

Abstract

8002 Background: Elotuzumab (elo) is approved for use in combination with lenalidomide (len) and dexamethasone (dex) for relapsed and refractory multiple myeloma (MM). This phase 2a study evaluated the efficacy and safety of elo in combination with len, subcutaneous bortezomib (bortez), and dex. Methods: The primary objective of this study was to determine the response rate of newly diagnosed, transplant-eligible MM patients (pts) after four cycles of therapy with elo plus len, bortez, and dex. Pts were newly diagnosed with MM by the revised IMWG criteria. Elo was administered days 1, 8, and 15 of the first two 28 day cycles and days 1 and 11 in cycles 3 and 4. Following cycle 4, pts underwent stem cell mobilization and could then proceed with either autologous stem cell transplant (ASCT) or defer transplant and receive four more cycles of induction therapy with elo plus len, bortez, and dex. Following either ASCT or 8 cycles of induction chemotherapy, pts transitioned to risk-adapted maintenance with elo, len, and dex plus every other week bortez (pts with high-risk cytogenetics, ISS stage II or III) or elo, len, dex (all others). Responses were assessed by the modified Uniform Response Criteria and toxicities graded based on NCI-CTCAE V4. Results: 41 patients with a median age of 60 were enrolled and this analysis encompasses response data from 29 patients. The overall response rate (ORR) after four cycles was 100%, with 24% achieving a complete response (CR), 47% achieving a very good partial response (VGPR), and 29% a partial response (PR). The rate of VGPR or better was 71%. The median number of CD34+ stem cells collected was 10.3 x 10^6. The most frequent grade 3 or higher toxicities included thrombocytopenia (15%) and hypophosphatemia (12%). The rate of grade 3 or higher peripheral neuropathy was 2%. Two pts died while on study, one due to complications of septicemia and the other due to respiratory failure. Conclusions: The combination of elo plus len, bortez, and dex was effective in newly diagnosed, ASCT-eligible patients. The rate of high-grade toxicities was low, although there were two grade 5 events (septicemia and respiratory failure). Clinical trial information: NCT02375555.