According to the results of a new study, therapeutic combinations containing carfilzomib are safe and effective for frail patients with relapsed/refractory (R/R) multiple myeloma.
"Frail patients with multiple myeloma can be challenging to treat, as they are potentially less able to tolerate therapy, are more vulnerable to side effects, and have compromised physiological function," write the study's investigators, led by first author Thierry Facon, MD, Professor of Hematology at Lille University Hospital in Lille, France. "These challenges may be further compounded in the setting of relapsed and/or refractory disease, where exposure to prior therapy and development of comorbidities may reduce tolerability of treatments, potentially diminishing efficacy."
In a post hoc analysis of three phase 3 clinical trials, Dr. Facon and colleagues investigated the efficacy and safety of carfilzomib-based regimens in a subgroup of frail patients with R/R disease. The ASPIRE trial enrolled 792 patients with R/R multiple myeloma who were randomized to receive carfilzomib/lenalidomide/dexamethasone or lenalidomide/dexamethasone alone; ENDEAVOR enrolled 929 patients to receive carfilzomib/dexamethasone or bortezomib/dexamethasone; and ARROW enrolled 478 patients to receive carfilzomib/dexamethasone in a dose of 70 mg/m2 once weekly or 27 mg/m2 twice weekly. A total of 25%, 36%, and 29% of patients were classified as frail in ASPIRE, ENDEAVOR, and ARROW, respectively. Progression-free survival was the primary end point of all three trials, with secondary end points of overall survival, response rates, and incidence of adverse events.
In ASPIRE, median progression-free survival was higher among frail patients receiving carfilzomib/lenalidomide/dexamethasone compared with lenalidomide/dexamethasone alone (24.1 vs 15.9 months). Median overall survival was also improved in patients receiving the carfilzomib combination (36.4 vs 26.2 months). A similar proportion of patients experienced grade 3 or higher treatment-related adverse events (93% vs 94%), with treatment discontinuation occurring in 37% and 43% of patients receiving the carfilzomib combination compared with control, respectively.
In ENDEAVOR, frail patients receiving carfilzomib/dexamethasone experienced a median progression-free survival of 18.7 months, compared with 6.6 months for those receiving bortezomib/dexamethasone. Patients in the carfilzomib group also experienced a higher median overall survival (33.6 vs 21.8 months). Grade 3 or higher treatment-related adverse events occurred in 85% of patients receiving carfilzomib/dexamethasone and in 79% of those in the control group, with treatment being discontinued in 33% and 30%. In ARROW, median progression-free survival was also increased among frail patients receiving the once-weekly higher dose of carfilzomib/dexamethasone compared with the twice-weekly lower dose (10.3 vs 6.6 months), as was the overall response rate (56% vs 41%). Grade 3 or higher adverse events occurred more frequently in patients receiving the higher dose compared with the lower dose (81% vs 70%), with similar rates of treatment discontinuation (20% vs 18%).
"In this first reported analysis employing a frailty algorithm in R/R multiple myeloma, our results continue to show that the efficacy and safety of carfilzomib-containing regimens observed in the primary ASPIRE, ENDEAVOR, and ARROW studies is consistently maintained across subgroups," conclude Dr. Facon and colleagues in their publication in Blood Advances. "Regardless of frailty status, carfilzomib-based regimens should be considered as viable treatment options for patients with R/R multiple myeloma."
For More Information
Facon T, Niesvizky R, Mateos MV, et al (2020). Efficacy and safety of carfilzomib-based regimens in frail patients with relapsed and/or refractory multiple myeloma. Blood Adv, 4(21):5449-5459. DOI:10.1182/bloodadvances.2020001965
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