Elotuzumab in combination with bortezomib in patients with relapsed/refractory multiple myeloma: A phase I study.

Abstract

8003 Background: Elotuzumab is a humanized antibody against a cell surface glycoprotein, CS1, which is highly expressed in multiple myeloma (MM). This phase I study was designed to determine MTD, safety, PK and response of elotuzumab in combination with bortezomib in relapsed/refractory MM patients (pts) following 1-3 prior therapies. Methods: Four escalating doses of elotuzumab (2.5 mg/kg to 20 mg/kg) were administered on D 1 and 11 and bortezomib (1.3 mg/m2) on D 1, 4, 8 and 11 of a 21-day cycle. Pts with ≥ stable disease after 4 cycles continued treatment until progression. Key entry criteria included age ≥ 18 years; confirmed MM diagnosis with 1 to 3 prior therapies including prior bortezomib and refractory MM; measurable M-protein in serum and/or urine. Results: In this fully enrolled study, 28 MM pts were treated; 3 each at 2.5, 5 and 10 mg/kg and 19 at 20 mg/kg elotuzumab. The 26 pts with completed analysis had a median of 3.4 years from initial MM diagnosis and a median of 2 prior lines of therapy. Eight pts (31%) had previously been treated with bortezomib and nine (35%) were refractory to the last MM therapy. No DLT was observed during the first treatment cycle and the MTD was not reached. Twelve SAEs were reported in 9 pts; two G3 events, chest pain and gastroenteritis, were assessed as elotuzumab- related. Unrelated SAEs included G4 hypercalcemia, G3 myocardial infarction, sepsis, vomiting, pneumonia (2 pts), G2 dehydration, G1 ileus and G1 incoherence. Most common AEs included fatigue, diarrhea, nausea, thrombocytopenia, constipation, anemia, peripheral neuropathy, lymphopenia, neutropenia, and leukopenia. Best response (≥ MR) by combined EBMT and uniform criteria in 20 evaluable pts with ≥ 2 treatment cycles was 60% including 40% ≥ PR. Median time to progression (TTP) is currently 9.6 months. Preliminary analysis of bone marrow plasma cells indicated that ≥ PR correlate well with complete or near complete saturation of CS1 sites by elotuzumab. Conclusions: The combination of elotuzumab with bortezomib has a manageable safety profile and shows encouraging activity in relapsed and refractory MM with ≥MR in 60% pts and a median TTP of 9.6 months. Updated safety and efficacy data will be presented at the meeting. Author Disclosure Employment or Leadership Position Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Facet Biotech Bristol-Myers Squibb, Celgene, Centocor Ortho Biotech, Exelixis, Millennium, Novartis, PDL BioPharma Facet Biotech Bristol-Myers Squibb, Celgene, Centocor Ortho Biotech, Exelixis, Millennium Celgene, Facet Biotech, Millennium, Novartis