FDA Approves Once-Weekly Dosing Regimen for Multiple Myeloma Treatment

Officials with the FDA have approved a supplemental New Drug Application (sNDA) to expand the use of carfilzomib (Kyprolis, Amgen) to include a once-weekly dosing option in combination with dexamethasone for patients with relapsed or refractory multiple myeloma, according to a press release.

Specifically, the expanded use includes a once-weekly 70 mg/m² dose of carfilzomib in combination with dexamethasone (once-weekly Kd70), Amgen announced.

Multiple myeloma, which remains an incurable disease, is marked by a recurring pattern of remission and relapse. The sNDA approval offers patients an alternative, more convenient dosing regimen for their treatment.

The expanded approval is based on data from the phase 3 ARROW clinical trial, which evaluated the once-weekly dosing regimen for carfilzomib in combination with dexamethasone compared with a twice-weekly dosing regimen. The trial included 478 patients with relapsed or refractory multiple myeloma who have received at least 2 or 3 prior lines of therapy, including a proteasome inhibitor and an immunomodulatory agent.

Patients in the trial received either a 30-minute infusion of once-weekly carfilzomib (20 mg/m² on day 1 of cycle 1; 70 mg/m² on days 8 and 15 of cycle 1; and 70 mg/m² on days 1, 8 and 15 of subsequent cycles) with dexamethasone (40 mg) or a 10-minute infusion of twice-weekly carfilzomib (20 mg/m² on days 1 and 2 of cycle 1; 27 mg/m² on days 8, 9, 15 and 16 of cycle 1; and 27 mg/m² on days 1, 2, 8, 9, 15 and 16 of subsequent cycles) with dexamethasone (40 mg).

According to the trial results, patients treated with the once-weekly dosing regimen achieved a statistically significant 3.7-month improvement in progression-free survival (PFS) compared with the Kd27 twice-weekly regimen (median PFS 11.2 months for once-weekly Kd70 versus 7.6 months for twice-weekly Kd27; HR=0.69; 95% CI: 0.54-0.88; one-sided p=0.0014). The overall response rate in patients treated with once-weekly Kd70 was 62.9% versus 40.8% for those treated with twice-weekly Kd27. Additionally, 7.1% had complete responses or better in the once-weekly group versus 1.7% in the twice-weekly group in the refractory patient population.

The overall safety profiles of the 2 patient groups in the trial were comparable, with no new safety risks identified in the once-weekly arm, according to Amgen. The most frequently reported treatment-emergent adverse events in either treatment arm were anemia, diarrhea, fatigue, hypertension, insomnia, and pyrexia.

“The availability of a more convenient once-weekly dosing regimen, with superior efficacy, comparable safety, and longer duration of therapy versus the twice-weekly regimen studied in the trial could allow patients to spend more time outside of the infusion center,” David S. Siegel, MD, PhD, chief of the Division of Multiple Myeloma at John Theurer Cancer Center at Hackensack University Medical Center, said in a press release.

The sNDA was reviewed by the FDA under the agency’s Oncology Center of Excellence Real-Time Oncology Review and Assessment Aid pilot programs.

Reference

FDA Approves KYPROLIS (carfilzomib) Once-Weekly 70 mg/m2 In Combination With Dexamethasone (Kd70) For Patients With Relapsed Or Refractory Multiple Myeloma [news release]. https://bit.ly/2DKKjKf. Amgen’s website. Accessed October 1, 2018.