FDA OKs Darzalex as Combination Therapy for Relapsed or Refractory Myeloma Patients

The U.S. Food and Drug Administration (FDA) has approved Darzalex (daratumumab), in combination with Revlimid (lenalidomide) and dexamethasone, or Velcade (bortezomib) and dexamethasone, for multiple myeloma patients who have received at least one prior therapy.

Clinical studies have revealed that adding Darzalex to Revlimid and dexamethasome in myeloma patients with a median of one prior therapy reduced the risk of disease progression or death by 63%. Adding Darzalex to Velcade and dexamethasone in patients who received a median of two prior therapies reduced the risk by 61%.

The recent approval comes just three months after the submission of a supplemental Biologics License Application (BLA) to the FDA in August. It was based on data from two Phase 3 clinical studies; the POLLUX (MMY3003) trial, and the CASTOR (MMY3004) study.

The open-label POLLUX trial (NCT02076009) was designed to compare the efficacy of the Darzalex, Revlimid, and dexamethasome triple combo, with that of Revlimid plus dexamethasone in patients with relapsed or refractory multiple myeloma. After a median follow-up of 13.5 months, median progression-free survival (PFS) was 18.4 months in the control arm, and not reached in the Darzalex arm. Overall response rate (ORR) also was increased in the Darzalex group (91% vs. 71%), with both higher rates of complete response (25% vs. 12%) and very good partial responses (32% vs. 24%).

The open-label CASTOR trial (NCT02136134) assessed the triple combination of Darzalex, Velcade, and dexamethasone, versus Velcade and dexamethasone alone in patients with relapsed or refractory multiple myeloma. After a median follow-up of 7.4 months, the median PFS was 7.2 months in the control arm and not reached in the Darzalex arm. Similar to what was seen in the POLLUX trial, ORR also was increased in the Darzalex group (79% vs. 60%), with twice as many complete responses (14% vs. 7%) and very good partial responses (38% vs. 19%) than the control group.

“While tremendous progress in the treatment of multiple myeloma has been made in the past decade, patients and their physicians continue to need new treatment options,” said Meletios A. Dimopoulos, MD, in a press release. Meletios is in the Department of Clinical Therapeutics, National and Kapodistrian University of Athens School of Medicine, Alexandra General Hospital, Athens, Greece and a Darzalex clinical trial investigator.

“With Darzalex, we have a potential new backbone therapy, which has shown pronounced efficacy as either a single agent or in combination with standard of care regimens. The addition of Darzalex also significantly improved progression-free survival in combination with two of the most widely used treatment classes, making it a versatile option for patients who have received at least one prior therapy,” he said.

In November 2015, Darzalex became the first CD38-targeting antibody to be approved anywhere in the world. It was approved as a monotherapy for myeloma patients who have received at least three prior lines of therapy, including a proteasome inhibitor, such as Velcade, and an immunomodulatory agent, such as Revlimid.