Blood cancers

Switch to once-weekly carfilzomib looks promising in multiple myeloma


Once-weekly carfilzomib appears to be more effective than the standard twice-weekly regimen for patients with relapsed or refractory multiple myeloma.

The findings from the ARROW study, presented at ASCO 2018 and published concurrently in The Lancet Oncology, support a change to a more convenient, sustainable dosing schedule for patients.

The open label, phase 3 trial compared a weekly dose of carfilzomib at 70 mg/m2 with what was the most common twice-weekly regimen of 27 mg/m2 of carfilzomib. Patients in both arms also received dexamethasone.

The trial comprised almost 500 patients from 118 sites in North America, Europe and Asia. Patients had received two to three prior therapies and had prior exposure to a proteasome inhibitor and an immunomodulatory drug.

Patients receiving the proteasome inhibitor once a week had a progression-free survival of 11.2 months compared to 7.6 months with the twice-weekly regimen.

Progression-free survival was also longer with once-weekly treatment in pre-specified sub-groups of patients including those with high-risk cytogenetics.

The overall response rate was 62.9% with once-weekly treatment compared to 40.8% with twice-weekly treatment.

“Furthermore, best responses, including complete response or better and very good partial response or better were higher in the once weekly group. These results are encouraging as a positive relationship between depth of response and improved survival has been shown in several phase 3 studies,” the Lancet Oncology article said.

Co-lead author Dr Maria-Victoria Mateos, from Hospital Clinico Universitario de Salamanca-IBSAL in Spain, told ASCO 2018 that the safety findings ‘were consistent with the known safety profile of carfilzomib’ and that ‘no new risks were identified’.

The rate of grade 3 or higher adverse events was 67.6% in the once-weekly group versus 61.7% in the twice-weekly arm; treatment-related grade 5 adverse events were 2.1% in the once-weekly group and 0.9% in the twice-weekly group.

A Comment article in the journal said consecutive-day, twice-weekly intravenous infusions of carfilzomib were a substantial burden for patients and healthcare providers.

However further studies were needed to establish standard carfilzomib doses and administration schedules including multi-agent protocols.

“Meanwhile, physicians will need to rely on careful scrutiny of adverse event profiles in patient sub-groups, as well as reports of real-world experiences.”

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