The FDA has approved an expansion of the prescribing information for carfilzomib to include its use with daratumumab and dexamethasone for the treatment of relapsed or refractory multiple myeloma.
The FDA has approved an expansion of the prescribing information for carfilzomib (Kyprolis, Amgen) to include its use with daratumumab (Darzalex, Amgen) and dexamethasone in a regimen of once weekly or twice weekly doses for the treatment of relapsed or refractory multiple myeloma (R/R MM) in patients who have received 1 to 3 prior lines of therapy.
Since MM is a blood cancer marked by a pattern of remission and relapse, patient outcomes can become worse with each relapse occurrence. Currently, there is also an increase in the use of frontline immunomodulatory drug-based (IMiD) therapies through progression, leading to an increase in the number of patients who will progress with these therapies becoming more likely to occur. This then demonstrates the need for efficacious lMiD-free regimens to be available for relapse upon their occurrence.
"Now, we can provide health care professionals and patients with an efficacious regimen with two dosing options at a critical time in a patient's treatment journey: first relapse," said David M. Reese, MD, executive vice president of Research and Development at Amgen, in a press release.
In particular, the carfilzomib with daratumumab and dexamethasone regimen presents an opportunity for an important potent triplet option for relapse occurrence following IMiD combination frontline therapy, explained Brian G.M. Durie, MD, chairman, International Myeloma Foundation, in the press release.
In the first phase 3 Candor randomized trial that compared carfilzomib, daratumumab, and dexamethasone versus carfilzomib and dexamethasone alone in patients with R/R MM, the results demonstrated a 37% reduction in the risk of disease progression or death in patients receiving both daratumumab and dexamethasone compared with dexamethasone alone.
"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 Saad Z. Usmani, MD, director of clinical research in hematologic malignancies and director of plasma cell disorders; clinical professor of medicine, Atrium Health's Levine Cancer Institute, in the press release. "As a clinician, having the [carfilzomib, daratumumab, and dexamethasone] 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."
In the phase 3 Candor trial, the safety of carfilzomib, daratumumab, and dexamethasone was found to be consistent with the safety profiles of each individual agent. The adverse events (AEs) most frequently reported (≥ 20% of subjects in either treatment arm) included infusion-related reactions, anemia, diarrhea, fatigue, hypertension, pyrexia, upper respiratory tract infection, thrombocytopenia, neutropenia, lymphopenia, cough, dyspnea, and insomnia, headache, and back pain.
Incidence of serious or fatal AEs at grade 3 or higher was noted to be greater in the carfilzomib, daratumumab, and dexamethasone treatment regimen compared with the carfilzomib and dexamethasone treatment regimen, with arm infections being the most common reason for fatal treatment-emergent AEs.
In addition to the Candor trial, the open-label, multi-cohort phase 1b Equuleus trial supported the Candor trial’s findings to expand carfilzomib’s prescribing information to include once-weekly dosing of carfilzomib within the daratumumab and dexamethasone regimen. Additionally, the safety and efficacy of carfilzomib, daratumumab, and dexamethasone was assessed in the Equuleus trial among patients with R/R MM using a once-weekly dosing regimen for carfilzomib.
FDA Approves New carfilzomib Combination Regimen With daratumumab And Dexamethasone In Both Once- And Twice-Weekly Dosing Regimens. Thousand Oaks, CA: Amgen; August 20, 2020. Accessed August 21, 2020.