Author(s): S. Lonial, R. Vij, J. Harousseau, T. Facon, P. Moreau, X. Leleu, C. Westland, A. K. Singhal, S. Jagannath

ABSTRACT:

Background: Elotuzumab is a humanized antibody against CS1, a cell surface glycoprotein, which is highly expressed in multiple myeloma (MM). In mouse xenograft MM model, elotuzumab demonstrated significantly enhanced anti-tumor activity when combined with lenalidomide (len) compared to len alone. The study objectives were to evaluate the MTD, safety, PK and efficacy of elotuzumab in combination with len and low dose dexamethasone (dex).

Methods: Len (25 mg PO) was given on Days 1-21 of a 28-day cycle. Elotuzumab (IV infusion) in 3 escalating dose cohorts (5, 10 and 20 mg/kg) was given weekly for the first two cycles and then every other week of subsequent cycles. Dex was given weekly at 40 mg PO. First 5 patients were treated for 6 months before a protocol amendment to continue treatment until progression.

Results: A total of 29 patients (pts) with a median age of 60 years were enrolled; 28 pts received study drug. Pts had a median of 3 prior MM treatments including thalidomide (59%), bortezomib (69%) or len (21%) with 41% pts refractory to their last MM therapy. Three pts each were treated at 5 and 10 mg/kg and 22 pts at 20 mg/kg elotuzumab. No DLT was observed during dose-escalation and no MTD was established. Two pts in the 20 mg/kg cohort discontinued due to infusion reactions, one G 4 allergic reaction and another G 3 stridor. Additional SAEs (1 each) included G 2 atrial fibrillation (related to len/dex) and unrelated G 4 ruptured diverticulum, G 3 neutropenic fever, sepsis, enteritis and diarrhea. Other common AEs included fatigue, diarrhea, constipation, anemia, neutropenia, nausea, muscle spasm, pyrexia, asthenia and dyspnoea. The ORR by IMWG criteria in 28 treated pts was 82% (64% PR; 18% VGPR). Pts-naïve to prior len (22 pts) demonstrated ORR of 95% (73% PR; 23% VGPR). Median time to progression (TTP) following a median of 4.5 cycles is not yet reached. Phase 2 expansion has been initiated to further examine the efficacy and identify the optimal dose of elotuzumab.

Conclusions: The combination of elotuzumab with len/dex has a manageable safety profile and the ORR of 82% including 95% in len-naïve pts is encouraging. Updated safety and efficacy data including TTP will be submitted at a later date.