Darzalex (daratumumab)

Adding Darzalex (daratumumab) to the treatment of multiple myeloma with Velcade (bortezomib) and Decadron (dexamethasone) significantly improved progression-free survival in a clinical trial of patients who had relapsed or did not respond to standard treatment.

The study, “Daratumumab, Bortezomib, and Dexamethasone for Multiple Myeloma,” published in the New England Journal of Medicine, shows that the combination’s superiority in extending survival, however, comes at a cost, as side effects in patients receiving the combination were more common.

Darzalex, an antibody targeting the CD38 molecule on cancer cells, was approved by the U.S. Food and Drug Administration (FDA) for the treatment of relapsing multiple myeloma in November 2015. The study provided additional support for the effectiveness of the drug.

The Phase 3 clinical trial (NCT02136134) randomized 498 patients to receive either 1.3 mg of Velcade per square meter of body surface area and 20 mg of Decadron, given to 247 patients; or the two drugs together with an add-on of 16 mg per kg body weight Darzalex to 251 patients.

Patients in the Darzalex group received the drug once weekly during the first three 21-day study cycles, then once every three weeks during cycles 4-9, and then once every four weeks until disease progression, unacceptable side effects, or the patient wished to leave the study.

Researchers from the University of Turin in Italy report that at 12 months, patients in the Darzalex combination group had a progression-free survival rate of 60.7 percent, while the control group on Velcade and Decadron reached only 26.9 percent.

Following the patients for a median of 7.4 months, the control group had a median progression-free survival of 7.2 months, while it was not possible to calculate the median for the Darzalex patients, since so few had disease progression.

Also, the rate of overall response was higher among patients treated with Darzalex, (82.9 versus 63.2 percent), and more patients had at least a partial (59.2 versus 29.1 percent), or complete (19.2 versus 9 percent) response.

Patients in both groups had equally frequent side effects, but a greater proportion of severe side effects were seen in the Darzalex group, including loss of blood platelets, red blood cells, or white blood cells called neutrophils,

Nearly half of patients in this group also got reactions linked to the infusion of Darzalex, 98.2 percent of which occurred during the first infusion. These reactions were mostly mild or moderate, however.

“In the [Darzalex] group, deep, rapid, and durable responses were reported, with the rates of very good partial response or better and complete response or better approximately double those in the control group,” the researchers wrote.