ASH 2014: Strong Showing for Anti-CD38 Monoclonal Antibodies in Myeloma
An investigational new class of drugs, the anti-CD38 monoclonal antibodies, could be the next blockbuster agents in multiple myeloma, experts in this malignancy predicted at the 56th American Society of Hematology (ASH) Annual Meeting and Exposition.
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. Although the data reported at an ASH press briefing came only from phase Ib studies, it was considered impressive.
“These anti-CD38 monoclonal antibodies, I believe, will be blockbuster drugs and will be an important component to multiple myeloma treatment,” Thomas Martin, MD, of the University of California, San Francisco, predicted.
SAR650948 Study
Dr. Martin presented results for SAR650948, which was evaluated in a dose-escalation study in combination with a standard regimen of lenalidomide (Revlimid)/dexamethasone in 31 patients with relapsed/refractory disease (Abstract 83). There was no upper limit on number of prior lines of therapy.
“These were very heavily pretreated patients,” he noted. “More than 90% had prior lenalidomide, 90% had prior bortezomib [Velcade], about 30% had prior pomalidomide [Pomalyst], and 50% prior carfilzomib [Kyprolis]. Many were double-refractory.”
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 with immunomodulators.
Referring to the robust reduction in M protein, a marker of disease, Dr. Martin observed the waterfall plot to be “dramatic.” The majority of patients had some response, he said.
Median progression-free survival was 6.2 months, but had not been reached in patients who had received less than three previous treatments.
“SAR650984 in combination with lenalidomide and dexamethasone showed encouraging activity in this heavily pretreated population,” he said.
The addition of SAR650984 did not increase toxicity. The most common adverse events were mild fatigue, nausea, diarrhea, neutropenia, and upper respiratory infection. Two patients discontinued the drug due to infusion-related reactions, but most such reactions resolved after cycle one.
Daratumumab Study
Preliminary data for a second anti-CD38 antibody, daratumumab, were reported by Maria-Victoria Mateos, MD, PhD, of the University Hospital of Salamanca in Spain (Abstract 176). The presentation at the meeting will be given by Philippe Moreau, MD, of University Hospital of Nantes, France.
Daratumumab, which had shown single-agent activity, was combined with one of four standard regimens in the treatment of 18 newly diagnosed patients and 7 relapsed/refractory patients in the MMY1001 study. Regimens included bortezomib/dexamethasone, bortezomib/thalidomide (Thalidomide)/dexamethasone, bortezomib/melphalan/prednisone, and, for previously treated patients, pomalidomide/dexamethasone.
Fully 100% of newly diagnosed patients responded to daratumumab plus a standard regimen. The response rate was 50% in the relapsed group, Dr. Mateos reported.
“The addition of 16 mg/kg of daratumumab to the various backbones was well tolerated in all evaluable patients and did not result in significant additional toxicity,” she said. “There were some serious adverse events, but most were related to the backbone therapy.”
After a median treatment duration of 44 days, no additional toxicity was observed with the addition of daratumumab to these regimens. Four patients had infusion reactions, but these did not interrupt treatment. All other adverse events were consistent with those previously reported with the standard regimens, said Dr. Mateos.
Dr. Martin reported research funding from Sanofi and membership on a speakers bureau for Novartis. Drs. Moreau and Mateos reported honoraria from Janssen and membership of a board of directors or advisory committee for Janssen. For full disclosures of the study authors, view the study abstracts.
The content in this post has not been reviewed by the American Society of Clinical Oncology, Inc. (ASCO®) and does not necessarily reflect the ideas and opinions of ASCO®.
