Phase I trial of elotuzumab, lenalidomide, and low-dose dexamethasone in patients with relapsed or refractory multiple myeloma.

Abstract

8076 Background: Elotuzumab is a humanized monoclonal IgG1 antibody targeting human CS1, a cell surface glycoprotein that is highly and uniformly expressed on multiple myeloma (MM) cells with limited expression in normal tissues. In preclinical studies lenalidomide enhanced the antitumor activity of elotuzumab. Methods: This phase I study assessed the maximum tolerated dose (MTD), safety, and efficacy of elotuzumab with lenalidomide plus low-dose dexamethasone in patients with relapsed/refractory MM. Three patient cohorts were treated with escalating doses of elotuzumab (5, 10, and 20 mg/kg IV on days 1, 8, 15, and 22 every 28 days in the first 2 cycles, and days 1 and 15 of subsequent cycles), lenalidomide (25 mg PO days 1–21), and dexamethasone (40 mg PO weekly). After the first 5 patients received up to 6 cycles of therapy, the protocol was amended to permit treatment until disease progression. Results: Twenty-nine patients were enrolled with a median age of 60 years (range, 41–83) and a median of 3 prior therapies (range, 1–10). At the time of analysis patients had received a median of 10.5 treatment cycles and 25 doses of elotuzumab, and 11 patients continued to receive treatment. During the dose escalation phase, there were no DLTs and the MTD was not reached. Among 28 treated patients, the most frequent grade 3/4 treatment emergent toxicities were neutropenia (36%) and thrombocytopenia (21%); 2 patients experienced 3 serious infusion-related reactions (1 patient with a grade 4 hypersensitivity reaction and 1 with two grade 3 stridor events) during the first treatment cycle. A partial response or better was achieved by 82% of all patients, 95% of lenalidomide-naïve patients (n=22), 94% of those with prior thalidomide (n=16), and 83% of those refractory to the most recent MM therapy (n=12). The median time to response was 7 weeks. For the 20 mg/kg cohort, the median time to progression has not been reached at a median 12.7 months follow-up. Updated results will be presented at the meeting. Conclusions: A phase II trial of elotuzumab (10 vs 20 mg/kg) with lenalidomide/dexamethasone is ongoing.