FDA Approves Once-Weekly Carfilzomib for Myeloma

October 15, 2018

FDA approves once-weekly carfilzomib/dexamethasone combo for relapsed or refractory multiple myeloma.

The US Food and Drug Administration (FDA) has expanded the approval of carfilzomib (Kyprolis, Amgen) to include a once-weekly dosing option when combined with dexamethasone for patients with relapsed or refractory multiple myeloma.

Carfilzomib was previously approved as a twice-weekly monotherapy in patients with relapsed or refractory disease.

The expanded approval is based on interim data from the phase III ARROW trial presented earlier this year at the 2018 American Society of Clinical Oncology (ASCO) annual meeting and published in Lancet Oncology. Results showed that once-weekly carfilzomib resulted in a superior progression-free survival (PFS) and overall response rate compared with the twice-weekly regimen.

The study compared once-weekly carfilzomib with twice-weekly carfilzomib in 478 patients with heavily pretreated disease including exposure to a proteasome inhibitor and immunomodulatory agent. Carfilzomib was given in combination with dexamethasone.

The median PFS in the once-weekly group was 11.2 months compared with 7.6 months for the twice-weekly regimen, a 3.7 month improvement (hazard ratio [HR], 0.69; 95% CI, 0.54–0.88; P < .0001). Complete responses occurred in 7.1% of patients assigned to the once-weekly arm compared with only 1.7% in the twice-weekly arm.

Despite a longer mediation duration of treatment in the once-weekly arm, rates of any-grade, grade III or worse, or serious adverse events were only slightly higher in the once-weekly arm compared with twice- weekly.

Commenting on the approval, Maria-Victoria Mateos, MD, PhD, of Hospital Clinico Universitario de Salamanca-IBSAL, Salamanca, Spain, said that carfilzomib showed a favorable risk/benefit profile for patients with relapsed or refractory disease, with an improved response rate and PFS with no additional toxicity.

“[This] provides a more convenient schedule and can improve access to an efficacious therapy for patients unable to make twice-weekly visits to the clinic,” Mateos told Cancer Network.

Carfilzomib/dexamethasone is also under investigation in combination with daratumumab in patients with lenalidomide refractory multiple myeloma. Results presented at the 2018 ASCO Annual Meeting showed that the combination had promising efficacy in the MMY1001 trial, with a median PFS of 9.9 months and a 66% response rate.