FDA Approves Kyprolis in Combination with Darzalex and Dexamethasone for Relapsed/Refractory Multiple Myeloma

The Food and Drug Administration (FDA) has approved the expansion of Kyprolis (carfilzomib) in combination to with Darzalex (daratumumab) plus dexamethasone in once- and twice-weekly dosing regimens for the treatment of patients with relapsed or refractory multiple myeloma who have received a maximum of three prior lines of therapy, according to the agent’s manufacturer Amgen.

“This expanded approval for Kyprolis demonstrates a leap forward in the treatment paradigm for this complex disease by combining two potent agents in their respective drug classes indicated for patients with relapsed or refractory multiple myeloma," said Amgen’s executive vice president of research and development Dr. David M. Reese, in a company-issued press release.

The agency based its approval on data from the phase 3 CANDOR trial, as well as the phase 1b EQUULEUS trial.

Results from the CANDOR trial showed that the addition of Kyprolis to Darzalex and Dexamethasone demonstrated a 37% reduction in the risk of disease progression or death. At a median follow-up of 17 months, a median progression-free survival was not yet reached in the triple therapy arm (312 patients) versus 15.8 months in the Darzalex and dexamethasone alone group (154 patients). However, a median overall survival was not reached in either treatment arm.

Patients who received the triple therapy reached an overall response rate of 84.3% versus 74.7% of patients who received Darzalex and dexamethasone alone.

A total of 308 patients in the triple therapy arm and 153 patients in the Darzalex and dexamethasone arm were evaluated for safety.

The overall toxicity profile with both regimens was comparable to what has been previously reported with the agents as single agents, according to the release. Patients who received the triple therapy were on treatment for a median of 70.1 weeks vs. 40.3 weeks for those who received Darzalex and dexamethasone.

Serious or severe side effects were reported in 56.2% of patients who received the triple therapy vs. 45.8% in the Darzalex and dexamethasone group.

The combination regimen has been approved in two Kyprolis dosing regimens: 70 mg/m2 once weekly and 56 mg/m2 twice weekly.

“Despite ongoing advances in the treatment of multiple myeloma, the disease remains incurable and is especially challenging for patients who relapse or become refractory to established therapies,” said Dr. Saad Z. Usmani, director of clinical research in hematologic malignancies at Atrium Health's Levine Cancer Institute, in the release. “As a clinician, having the (triple therapy) regimen as an option means we can now combine two efficacious, targeted agents in a new, immunomodulatory drug-free triplet regimen that has demonstrated deep and durable responses for patients upon relapse.”