Daratumumab-Based Combination Regimen Submitted for FDA Approval in Relapsed/Refractory Multiple Myeloma

Janssen announced yesterday the submission of a supplemental biologics license application to the FDA seeking approval of daratumumab (Darzalex, Janssen) in combination with carfilzomib (Kyprolis, Amgen) and dexamethasone for relapsed/refractory multiple myeloma (RRMM).

The submission is supported by findings from the phase 3 CANDOR study presented at the 2019 American Society of Hematology Annual Meeting, where the use daratumumab with carfilzomib and dexamethasone (KdD) was found to boost survival benefits for patients with RRMM, including those who have taken lenalidomide. Lenalidomide is an agent currently involved in 4 of the 6 treatment combinations approved for RRMM, but a majority of patients have exhibited disease progression on the agent or bortezomib, potentially due to the toxicity of both components.

In multiple myeloma (MM) cells, the surface protein CD38 presents in high numbers regardless of disease stage. Daratumumab, the first monoclonal antibody for MM, is the only CD38-directed antibody approved to treat MM, which binds to CD38 and inhibits tumor cell growth causing myeloma cell death. The agent began development in August 2012 and received its first approval in November 2015.

Craig Tendler, MD, vice president of Late Development and Global Medical Affairs for Janssen, highlighted the importance of increasing treatment options for patients with RRMM. “While we continue to make important strides in the treatment of multiple myeloma, unfortunately most patients will relapse at some point, so it is important that physicians have multiple treatment options and regimens for patients,” he said.

In the open-label, phase 3 CANDOR study, funded by Amgen, researchers compared the efficacy of KdD with that of carfilzomib and dexamethasone alone (Kd) among patients with RRMM on the primary endpoint of progression-free survival, characterized by time from randomization until disease progression or death from any cause. In the 446 participants randomized 2:1 to either KdD or Kd, those administered KdD exhibited a significant 37% reduction in the risk of disease progression or death.

Results from the secondary endpoints of the study, which were overall response rate (ORR), undetectable minimal residual disease (MRD) at 12 months, and overall survival (OS), additionally showed the effectiveness of KdD compared with Kd in ORR (84.3% vs 74.7%, respectively) and MRD (12.5% vs 1.3%). No differences in OS were shown based on the data analyzed to that point.

“The results from the CANDOR study support the potential benefit of this Darzalex-based combination regimen for patients with multiple myeloma who have relapsed from prior treatment,” said Tendler.