27 August 2015. An early-stage clinical trial shows some patients receiving an engineered antibody to attack multiple myeloma cancer cells experienced at least a partial remission of their disease. Results of the study, led by oncologist Paul Richardson of Dana-Farber Cancer Institute and Harvard Medical School, appeared yesterday in New England Journal of Medicine.
Multiple myeloma is a cancer of plasma cells, white blood cells helping fight infections by making antibodies that recognize invading germs. The disorder causes cancerous cells to accumulate in the bone marrow, crowding out healthy plasma cells. Instead of antibodies, the malfunctioning cancer cells produce abnormal proteins that cause kidney problems and other disorders. American Cancer Society expects nearly 27,000 new cases of multiple myeloma to occur in the U.S. this year, causing more than 11,000 deaths.
The clinical trial tested daratumumab, an antibody designed to specifically target CD38, an enzyme over-expressed and appearing on the surface of multiple myeloma cancer cells. Daratumumab, developed by the biotechnology company Genmab A/S in Copenhagen, Denmark, binds to and attacks the cancer cells through various mechanisms. Genmab reports in preclinical tests daratumumab killed multiple myeloma cells both on its own and with other therapies. Janssen Biotech, a division of Johnson & Johnson, licensed daratumumab from Genmab in 2012, and sponsored the clinical trial with Genmab.
The trial enrolled participants with multiple myeloma that either relapsed or failed to respond to earlier treatments. Of the 104 participants, a group of 32 patients tested daratumumab given as an infusion at gradually larger dosage levels to determine the therapy’s safety. Another 72 individuals were tested with daratumumab at two dosage levels — 8 and 16 milligrams per kilogram of weight — and different intervals, from weekly to monthly, for up to two years. All patients were first treated with anti-inflammatory drugs to reduce adverse reactions to the infusions.
The study’s primary objective was to evaluate daratumumab’s safety, but the researchers also looked at participants’ clinical responses to the treatments. Of the 42 participants in the group receiving the highest dosage levels of daratumumab, 16 milligrams per kilogram, 36 percent reported at least a partial response to the drug, defined as some tumor size reduction. Median progression-free survival time for this group of participants was 5.6 months. Of those receiving the lower dosage, 10 percent experienced at least a partial response. Of the patients in either group reporting a response, about two-thirds (65%) experienced no progression of their disease after one year.
The study team reported that daratumumab was generally well tolerated by participants. Of those experiencing a reaction, 7 in 10 (71%) characterized the reactions as mild — generally fatigue, nasal congestion, and fever — with 1 percent (less than 5% overall) reporting severe reactions, including pneumonia and low blood platelet count.
“As a single-agent therapy, daratumumab showed significant promise against difficult-to-treat disease in our patients with advanced myeloma and who have few other therapeutic options,” says Richardson in a Dana-Farber statement. “Because it targets a key receptor and works through different mechanisms than other available agents, it clearly has merited comprehensive testing in larger clinical trials.”
Genmab says daratumumab is being tested in late-stage clinical trials among larger numbers of participants having multiple myeloma, with studies of the drug to treat non-Hodgkin’s lymphoma also planned. Daratumumab received fast-track and breakthrough designations from the U.S. Food and Drug Administration, and orphan drug status from FDA and European Medicines Agency.
Read more:
- Early Trial Results Targeting Cancer Mutations Promising
- Trial Shows Engineered T-Cells Act on Multiple Myeloma
- FDA Clears Biotech Cancer Therapies for Early Trials
- Antibody Improves Lung Cancer Survival Time in Trial
- Astellas Getting First Access to Leukemia Antibody
Disclosure: The author owns shares in Johnson & Johnson.
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