Early reports from ongoing phase 1b clinical trials suggest that monoclonal antibodies that bind to the CD38 protein on multiple myeloma cells yield responses in patients.

Monoclonal antibodies have become a mainstay of cancer treatment. The FDA has approved 17 for various malignancies, but none so far for multiple myeloma, which is notoriously difficult to treat. However, early reports from ongoing phase 1b clinical trials suggest monoclonal antibodies that bind to CD38 on tumor cells can produce strong responses in patients.

“There is an unmet medical need in myeloma treatment,” says Thomas G. Martin, MD, of the University of California, San Francisco, the principal investigator for a phase 1b trial of SAR650984 (Sanofi), an anti-CD38 drug. Martin presented his group's early findings in December at the 2014 annual meeting of the American Society of Hematology (ASH) in San Francisco. He says monoclonal antibodies such as those that target CD38 are poised to be the blockbuster drugs needed to improve treatment for patients with the disease.

In the SAR650984 trial, 31 patients with relapsed or refractory multiple myeloma received one of three doses of the drug every 2 weeks, in addition to lenalidomide, an immunomodulatory drug, and dexamethasone, a steroid. Martin and his team observed responses at every dose level, with the highest response rate in the group receiving the highest dose. After a median follow-up of 6 months, the overall response rate was 58% (18 patients), and the median progression-free survival was 6.2 months.

Daratumumab (Genmab/Janssen), another anti-CD38 drug, also “holds up a flag” to trigger an immune response, says Maria-Victoria Mateos, MD, of the University Hospital of Salamanca in Spain. It was designated a breakthrough therapy by the FDA in May 2013 for patients with multiple myeloma who have received at least three prior lines of therapy. The designation expedites the review process for drugs that treat serious conditions with an unmet need.

Mateos leads one of four arms of an ongoing phase 1b trial to test the safety of daratumumab in newly diagnosed patients as well as those with relapsed or refractory disease. Early results from that trial were presented at ASH by the study's principal investigator, Philippe Moreau, MD, of University Hospital of Nantes in France. Patients are treated with daratumumab combined with one of four treatment regimens: bortezomib and dexamethasone; bortezomib, thalidomide, and dexamethasone; bortezomib, melphalan, and prednisone; or pomalidomide and dexamethasone.

Mateos says that although the study is small and it's too early to draw definitive conclusions from the data, the drug can be safely combined with existing regimens. The overall response rate among the 17 patients who received a regimen containing bortezomib was 100%. Half of the patients in the group that didn't receive bortezomib also responded to treatment. Mateos and her colleagues are now planning a randomized phase III trial.

The promising data from these trials have been a long time coming, says Martin, but they suggest that monoclonal antibodies may finally find a place in treatment regimens for myeloma, which remains incurable. “In multiple myeloma, we're about 10 years behind lymphoma in the use of these antibodies,” he says, “but we finally have some that work.”