An investigational new class of drugs, the anti-CD38 monoclonal antibodies, could be the next major advance in the treatment of multiple myeloma. These findings were presented at the 56th American Hematological Society Annual Meeting and Exposition, December 6–9, 2014, in San Francisco, California.
Multiple myeloma is a cancer of plasma cells, which are a special type of white blood cell that are part of the body’s immune system. In the U.S., approximately 70,000 people are living with multiple myeloma and approximately 24,000 new individuals are diagnosed annually. Patients with multiple myeloma have increased numbers of abnormal plasma cells that may produce increased quantities of dysfunctional antibodies detectable in the blood and/or urine. Patients with multiple myeloma who have become refractory—or resistant—to the drugs Revlimid® (lenalidomide) and Velcade® (bortezomib) have limited treatment options. There is no standard treatment for these patients and they typically have a poor prognosis.
Daratumumab is a novel anti-CD38 monoclonal antibody that had previously demonstrated single-agent activity in the treatment of multiple myeloma. Anti-CD38 antibodies target multiple myeloma cells by binding to the CD38 antigen expressed on the cell surface and then signaling the patient’s immune system to attack the tumor. In the current study, daratumumab was combined with one of four standard regimens and evaluated for the treatment of 18 newly diagnosed patients and 7 relapsed/refractory patients. Overall 100% of newly diagnosed patients and 50% of those with relapsed or refractory disease responded to treatment. Importantly, the addition of daratumumab was well tolerated in all evaluable patients and did not appear to result in significant additional side effects.1
The results of a second clinical trial evaluating a novel anti-CD38 monoclonal antibody SAR650948 were also reported at ASH. SAR650948 was evaluated in a phase 1b dose-escalation study in combination with a standard regimen of Revlimid® and dexamethasone in 31 patients with relapsed/refractory myeloma.2
The combination produced responses in 58% of patients overall, rising to 63% in patients receiving the highest dose, 10 mg/kg every 2 weeks. A 50% response rate was observed in patients who had relapsed on or were refractory to previous treatment.
Both Daratumumab and SAR650984 showed encouraging activity in the management of multiple myeloma. These anti-CD38 antibodies that target multiple myeloma cells by binding to the CD38 antigen expressed on the cell surface and then signaling the patient’s immune system to attack the tumor may represent the next advance in myeloma treatment and will continue evaluation in ongoing clinical trials.
1. Moreau P, Mateos M-V, Blade J, et al. 176 An Open-Label, Multicenter, Phase 1b Study of Daratumumab in Combination with Backbone Regimens in Patients with Multiple Myeloma. Presented at the 56th Annual Meeting of the American Society of Hematology. December 6-9, 2014. Abstract 176.
2. An G, Jiang H, Acharya C, et al. 4729 SAR 650984, a Therapeutic Anti-CD38 Monoclonal Antibody, Blocks CD38-CD31 Interaction in Multiple Myeloma. Presented at the 56th Annual Meeting of the American Society of Hematology. December 6-9, 2014. Abstract 83.
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