Once-Weekly Carfilzomib as Safe, Effective as Twice-Weekly Treatment in Newly Diagnosed MM

New research is indicating that patients newly diagnosed with multiple myeloma can be treated with carfilzomib (Kyprolis) once a week instead of twice. According to researchers, once-weekly 70 mg/m² of the proteasome inhibitor is as safe and effective as twice-weekly 36 mg/m² while also providing a more convenient treatment schedule.

Currently, carfilzomib is indicated for twice-weekly treatment of patients with relapsed and/or refractory multiple myeloma, but given its demonstrated efficacy, the treatment has been assessed as up-front therapy in combination with lenalidomide-dexamethasone or with alkylating agents, such as melphalan-prednisone, for newly diagnosed patients.

“Despite the great results yielded by the introduction of carfilzomib, treatment compliance and quality of life of young active patients, as well as the ones of elderly patients with reduced mobility, are burdened by the need for frequent visits to the outpatient clinic for carfilzomib dosing,” wrote the researchers. “In this view, a shift from the current-twice weekly to a once-weekly dosing schedule would decrease by 50% the patient visits to healthcare facilities, with a subsequent improvement in quality of life and a reduction in drug and healthcare costs.”

Pooling data from the phase 1/2 IST-CAR-561 and phase 2 IST-CAR-506 studies comparing once-weekly (70 mg/m²) and twice-weekly (36 mg/m²) treatment with carfilzomib plus cyclophosphamide and dexamethasone, the researchers identified transplant-ineligible patients with newly diagnosed multiple myeloma across 14 sites in Italy. The 199 patients received either once-weekly or twice-weekly treatment for 9 four-week induction cycles. Following the induction period, 90 patients received maintenance therapy with carfilzomib alone.

Data showed that there was no significant difference in progression-free survival (PFS) between the 2 treatment schedules, with a median PFS of 35.7 months among patients receiving once-weekly carfilzomib and a median PFS of 35.5 months among patients receiving twice-weekly treatment.

Following 3 years of follow-up, 47% and 49% of patients in the once-weekly and twice-weekly groups were alive and progression free, respectively. Median overall survival was not reached for either group, with 70% of patients in the once-weekly group and 72% of patients in the twice-weekly group being alive at 3 years.

Even when adjusting for age, frailty, and other factors, the researchers observed no significant differences in the risk of progression or death.

The most commonly reported adverse events included acute kidney injury and hypertension. These events led to a dose reduction of carfilzomib in 18 (29%) of patients receiving once-weekly treatment and in 17 (30%) patients receiving twice-weekly treatment. Meanwhile, 17 (27%) patients in the once-weekly group and 17 (30%) patients in the twice-weekly group had to discontinue therapy as a result of adverse events that included cardiac injury, infections, and thromboembolism.

“Of note, delivering 70 mg/m² of carfilzomib in a single dose did not increase the risk of grade 3-5 hematological (24% vs 30%) and non-hematological (38% vs 41%) adverse events, as compared to a twice-weekly administration of 36 mg/m² of carfilzomib,” explained the researchers, who added that no new cardiovascular safety risks were identified with the single dose.

Reference

Brighen S, Mina R, Petrucci M, et al. Once-weekly carfilzomib versus twice-weekly carfilzomib in patients with newly diagnosed multiple myeloma: a pooled analysis of two phase 1/2 studies [published online February 7, 2019]. Haematologica. doi: 10.3324/haematol.2018.208272.