Research suggests that adding a new drug – an anti-CD38 monoclonal antibody – to the standard therapy for multiple myeloma may be a viable and effective approach. This drug binds the CD38 antigen (expressed in myeloma cells) and then causes immune cells to attack the myeloma cells. The antibody binds to the surface of the cell and blocks the marker, saying “immune system, come attack me,” said Dr. Thomas Martin of the University of California. He presented early data from a trial of the monoclonal antibody SAR650984 in combination with lenalidomide and dexamethasone for relapsed/refractory multiple myeloma. This combination therapy had an overall remission rate of 58% in the Phase 1b dose escalation trial, which Dr. Martin described as a “pretty exciting response” given that 31 patients had received four prior therapies. Progression-free survival was 6.2 months. A total of 15 patients had progression-free survival events (1 non-treatment related death and 14 disease progression) with a median follow-up of 6 months. Very significantly, this combination therapy had an overall remission rate of 62.5% in patients who relapsed or were last refractory to treatment with lenalidomide therapy. Dr. Martin believes that anti-CD38 monoclonal antibodies are a good add-on drug to treat this cancer. He said, “I think the CD38 drug is a highly effective drug.” Another clinical doctor wasn’t so sure about that. Dr. Brad Kahl of the University of Wisconsin says it’s too early to call it a success. Dr. Martin says there is still an unmet medical need in myeloma, by which he means the therapy has significant efficacy for relapsed/refractory patients. According to Dr. Martin, this therapy is very effective in immune-mediated inflammatory diseases (thalidomide, lenalidomide, pomalidomide) and proteasome inhibitors (bortezomib and carfilzomib), extending survival from 3 to 7 or even 10 years. However, for relapsed/refractory patients who had extensive pretreatment, the average survival was about 9 months. In this study, patients with relapsed/refractory myeloma received one of three dose levels (3, 5 and 10 mg/kg) of SAR650984 every two weeks in combination with lenalidomide and dexamethasone. Patients receive intravenous SAR650984 on days 1,15 in increasing doses for a course of 28 days. Days 1-21 received lenalidomide 25 mg, with a dose adjustment to 10 mg if baseline creatinine clearance was ≤60 mL/min, and days 1,8,15 and 22 received dexamethasone 40 mg. Eighteen patients received the maximum tolerated dose of SAR650984 (10 mg/kg). As reported by Dr. Martin, approximately one-third (38%) of patients had infusion reactions during the first course, but as a result only 3% of patients discontinued treatment. The most common treatment-related adverse reactions (either grade) were fatigue (41.9%), nausea (38.7%), upper respiratory tract infection (38.7%), and diarrhea (35.5%).