Post-marketing surveillance data further confirmed carfilzomib to be a well-tolerated and promising option among patients with relapsed/refractory multiple myeloma, although investigators emphasize the importance of watching for cardiac comorbidities.
Carfilzomib (Kyprolis)–based therapy demonstrated efficacy and acceptable safety in a population of Japanese patients with relapsed/refractory multiple myeloma, according to results from a post-marketing surveillance study published in Future Oncology.
Treatment with the agent resulted in a 46.5% overall response rate (ORR; n = 444/954). Rates of response were 42.3% (n = 243/574) and 52.9% (n = 201/380) among patients who received carfilzomib, lenalidomide (Revlimid), and dexamethasone (KRd) and Kd, respectively. Among unevaluable patients who were excluded from the sample, the ORR was 62.6% (n = 444/709) in the overall cohort, 57.3% (n = 243/424) in the KRd group, and 70.5% (n = 201/285) in the Kd group.
In terms of safety, 63.5% of patients experienced adverse effects (AEs) of any grade and 44.6% experienced grade 3 or higher AEs. The most common treatment-related AEs included decreased platelet count (19.7%), decreased neutrophil count (9.1%), anemia (7.1%), decreased white blood cell count (5.8%), and heart failure (5.1%). Grade 3 or higher cardiac disorders were observed in 66 patients (6.7%). The overall recovery or improvement rate for all AEs was 77.3% and the mortality rate was 3.1% with the most common cause of death being cardiac disorders.
Serious AEs were reported in 37.7% of the overall patient population. Moreover, 67.5% of patients discontinued treatment, most commonly due to progressive disease (24.3%), AEs (23.5%), and a lack of response to carfilzomib (19.6%).
“The findings of this study are expected to serve as a guide for the proper use of carfilzomib regimens in clinical settings. It is hoped that understanding the characteristics of carfilzomib-related AEs will aid in the early detection and management of AEs in a healthcare setting,” the study authors wrote.
The multicenter, non-intervention, post-marketing trial took place in from August 2016 to May 2021 in Japan. Anonymous data were collected from 591 centers and included patients who received KRd or Kd. Treatment regimen chosen was based on physician discretion.
Those in the KRd group received carfilzomib on days 1, 2, 8, 9, 15, and 16 at a starting dose of 20 mg/m2 on days 1 and 2 of cycle 1 and a target dose of 27 mg/m2 thereafter. Carfilzomib was administered on days 1, 2, 15, and 16 from cycle 13 thereafter and 25 mg of oral lenalidomide was given from days 1 to 21. Dexamethasone was given at a dose of 40 mg on days 1, 8, 15, and 22 of each 28-day cycle. Those in the KRd arm underwent a maximum of 18 cycles of treatment or until discontinuation due to disease progression or unacceptable toxicity. In the Kd arm, carfilzomib was administered on days 1, 2, 8, 9, 15, and 16 at a dose of 20 mg/m2 on days 1 and 2 of cycle 1 followed by 56 mg/m2 subsequently, and dexamethasone was given at 20 mg on days 1, 2, 8, 9, 15, 16, 22, and 23.
Investigators reported that 3280 patients were included in the study, of whom 1012 patients completed survey forms. A total of 583 patients were treated with KRd and 397 were treated with Kd. The safety analysis included 991 patients and 954 were included in the efficacy analysis.
The median time from diagnosis to start of treatment was 1174.5 days. A total of 33.8% of patients in the Kd group were 75 years or older vs 19.2% in the KRd group. It was reported that 22.3% of patients had an ECOG performance status of 3 or more in the overall patient population.
Kawasaki A, Murakami H, Chou T, et al. Post-marketing surveillance of carfilzomib in Japanese patients with relapsed or refractory multiple myeloma. Future Oncol. 2022;18(24):2661-2674. doi:10.2217/fon-2022-0259