Once-weekly Kyprolis with Dexamethasone Approved in US for Relapsed or Refractory Multiple Myeloma

The U.S. Food and Drug Administration has approved a combination of once-weekly Kyprolis (carfilzomib), developed by Amgen, and dexamethasone for the treatment of multiple myeloma patients who failed prior therapies.

“In the fight against multiple myeloma, we are committed to continued evidence generation and innovation to serve patients. Kyprolis now offers patients with relapsed or refractory multiple myeloma the option of a more convenient dosing regimen that provides better outcomes with a comparable safety profile,” David M. Reese, MD, executive vice president of research and development at Amgen, said in a press release.

“We’re pleased that the FDA has recognized the importance of bringing more treatment options to cancer patients more quickly through its pilot programs and proud to participate with this Kyprolis data,” he said.

The application, which was granted priority review, was approved in just over a month under the FDA’s Oncology Center of Excellence Real-Time Oncology Review and Assessment Aid pilot programs, focusing on the early submission of the most relevant data for assessing the safety and effectiveness of a given therapy in order to make new treatments available to patients as soon as possible.

Kyprolis is a proteasome inhibitor. Proteasomes are barrel-shaped cellular structures that degrade misfolded, “used,” and nonfunctional proteins that have been molecularly tagged for destruction, acting as the cell’s protein garbage disposal.

Proteasome inhibitors are particularly useful for treating multiple myeloma because they stop the protein clearance process, leading to “bad” protein buildup, which causes malignant cells to blow up and die.

The FDA’s decision was based on data from Amgen’s Phase 3 ARROW trial (NCT02412878), aimed at comparing once-weekly and twice-weekly Kyprolis dosing, in combination with dexamethasone, in patients with multiple myeloma who had received between two and three prior lines of therapy, including Takeda‘s Velcade (bortezomib) and an immunomodulatory imide drug (IMiD).

Velcade is another proteasome inhibitor, while IMiD modulates the molecular interaction between myeloma cells and its surroundings, leading to decreased myeloma cell growth and survival.

A total of 478 subjects were randomized to receive a 30-minute infusion of Kyprolis (20 mg/m² on day 1 and 70 mg/m² thereafter) once a week plus dexamethasone (40 mg), or a 10-minute infusion twice weekly (20 mg/m² on day 1 and 27 mg/m² thereafter), also with dexamethasone.

The study’s primary goals were to determine the overall response rate and progression-free survival, which refers to the time from randomization to disease worsening or death due to any cause.

Results of the trial were published in The Lancet Oncology in the study, “Once weekly versus twice weekly carfilzomib dosing in patients with relapsed and refractory multiple myeloma (A.R.R.O.W.): interim analysis results of a randomised, phase 3 study.”

Findings were also presented by Amgen at the 54th Annual Meeting of the American Society of Clinical Oncology held in June in Chicago.

Researchers reported that patients treated with Kyprolis once a week lived significantly longer without disease progression than those receiving the biweekly treatment (11.2 months vs. 7.6 months).

Overall response rate was also higher in the once-weekly group than the biweekly one (62.9% vs. 40.8%).

Additionally, 7.1% of the participants in the once-weekly regimen had no evidence of disease after treatment, in contrast with only 1.7% of patients in the twice-weekly protocol.

In both groups, the most frequent side effects were anemia, diarrhea, fatigue, high blood pressure, insomnia, and fever.

“While great progress has been made in the last decade, multiple myeloma remains an incurable disease characterized by a recurring pattern of remission and relapse, and it is important that patients have treatment options that meet their individual needs,” said David S. Siegel, MD, PhD, chief of the Division of Multiple Myeloma at John Theuer Cancer Center at Hackensack University Medical Center.

“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,” he said.

Of note, Kyprolis is not approved for twice-weekly 27 mg/m² administration in combination with dexamethasone alone.