Darzalex Combo Therapy Extends Survival in Multiple Myeloma Treatment

The anti-CD38 monoclonal antibody daratumumab (Darzalex) was found to improve overall survival (OS) in patients with multiple myeloma who received 1 to 3 prior therapies (≥3), according to a study published in American Health & Drug Benefits.

In a phase 1/2 GEN503 trial that enrolled 31 patients with relapsed or refractory myeloma, participants were administered a combination therapy of Darzalex, lenalidomide (Revlimid), and dexamethasone, which showed a positive effect on the disease.

“It is very effective when given with other core treatments, with no added toxicity,” Torben Plesner, MD, said in the study.

The overall response rate (ORR) was 81%, with 34% of patients who achieved a complete response or better and 63% achieving a very good partial response (VGPR) or better. The median response duration was not met, while 91% of patients were free of disease progression at 12 months.

The OS data was immature, but it was reported that 90% of patients were alive and 72% were progression free at 18 months.

Common toxicity events included cough, diarrhea, muscle spasms, and neutropenia.

During the phase 1b MMY1001 trial, researchers evaluated the efficacy of Darzalex in combination with pomalidomide (Pomalyst) and dexamethasone in 98 patients with relapsed or refractory multiple myeloma who had at least 2 prior treatments. Most patients were refractory to a proteasome inhibitor and an immunomodulating drug.

The results of the study showed that the ORR was 71%, and was 67% in patients with double-refractory disease. Additionally, 43% of patients achieved VGPR or better and 73% of patients showed clinical benefit. There were 42% of patients who experienced serious adverse events.

“At a median follow-up of 4.2 months, 47 of 53 (89%) responders had not progressed,” said Ajai Chari, MD, in the study. “Daratumumab can be safely combined with pom/dex (pomalidomide plus dexamethasone). We observed no new safety signals.”

In another analysis that took data from 148 patients who received Darzalex in the GEN501 and SIRIUS trials, Darzalex monotherapy was found to be very active.

“Daratumumab induced rapid, deep, and durable responses in a heavily pretreated/highly refractory population,” said Saad Z. Usmani, MD in the study. “A remarkable depth of response was observed in patients who were refractory to newer agents, including pomalidomide and carfilzomib (Kyprolis).”

The ORR was 31% with 13% of patients achieving a VGPR or better. The median OS was 19.9 months with a 1-year survival rate of 69%. The median OS was not reached.

“(The daratumumab monotherapy) demonstrated significant activity, and not only this, but very prolonged duration of remission and overall survival in patients, even beyond the time when their response to anti-CD38 antibody is gone,” said Sagar Lonial, MD said in the study. “This suggests that immunomodulation may be an important part of the long-term outcome of patients.”