New Drug Therapy Puts Multiple Myeloma in Remission

Daratumumab causes the targeted killing of CD38-carrying tumor cells.

Patients with multiple myeloma will be pleased to hear about the new drug, daratumumab, and its success in treating the disease in clinical trials.

The breakthrough antibody therapy produced at least partial remissions in a third of patients with multiple myeloma, according to the report published in the New England Journal of Medicine.

The drug’s safety and efficacy yielded positive results as patients experienced only mild side effects, even at the highest doses permissible. The results strongly support testing in a larger group of patients in both phase 2 and 3 trials, the authors say.

“The treatment of multiple myeloma has improved significantly in recent years with the introduction of therapies such as proteasome inhibitors [which interfere with tumor cells’ protein-disposal system] and potent immune-modulatory agents,” said the senior author and lead investigator Paul Richardson, MD. “Unfortunately, while these agents generally work for a considerable period of time, resistance inevitably emerges, and far fewer treatment options are available in this setting. Therefore there is a great need to develop new treatments for this patient population in particular.”

Daratumumab works to target CD38, a protein strewn over the surface of myeloma cells but less prevalent on normal cells. The protein can act as a receptor and transmit signals to the cell interior.

Daratumumab was proven in laboratory studies to cause the targeted killing of CD38-carrying tumor cells via several potent techniques, some of which involved the immune system.

The study evaluated 72 patients, all of whom had received at least 2 prior lines of therapy and whose disease had relapsed and was unresponsive to treatment. In the initial phase, patients were slowly administered the medication and the drug gradually increased over time.

In the second phase, patients were given 2 doses tested at different administration schedules, weekly, twice monthly, and monthly, for up to 2 years.

Of the patients who received the higher dosage of daratumumab, 36% experienced durable responses, with 2 having complete remissions and 2 more whose remissions were of high quality, meaning they were “very good” partial responses. In this group, the average period of time it took to get the disease under control was 5.6 months.

Additionally, two-thirds of patients who benefited from the drug had no increased activity in the disease for at least 12 months.

Mild side effects of the drug included fatigue, nasal congestion, and fever, while other more severe side effects included pneumonia, low blood platelets, low white blood cell counts, anemia, and excess blood sugar.

However, the more severe side effects were not thought to be a direct effect of the antibody itself.

“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,” Richardson said. “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. Preliminary results from these studies have been very encouraging.”