Longer Progression-Free Survival With Once-Weekly Carfilzomib for Multiple Myeloma

By Reuters Staff

NEW YORK (Reuters Health) - Progression-free survival (PFS) in patients with relapsed and refractory multiple myeloma is longer when carfilzomib is given once rather than twice a week, according to results from an interim analysis of the ongoing ARROW study.

Carfilzomib, an irreversible and selective epoxyketone proteasome inhibitor, is approved as monotherapy and as combination therapy with dexamethasone or lenalidomide and dexamethasone for treating refractory or relapsed and refractory multiple myeloma. The earlier CHAMPION-1 study established the maximum tolerated weekly dose of carfilzomib at 70 mg/m2 administered as a 30-minute infusion.

Dr. Philippe Moreau from the University Hospital of Nantes, in France, and colleagues from 118 sites across North America, Europe and Asia compared the efficacy and safety of carfilzomib once weekly at 70 mg/m2 versus twice-weekly carfilzomib at 27 mg/m2 (the approved dose at the time of the study), both combined with dexamethasone, in 478 patients with relapsed and refractory multiple myeloma.

Median PFS, the primary endpoint, was significantly longer in the once-weekly group (11.2 months) than in the twice-weekly group (7.6 months), the researchers report in The Lancet Oncology, online June 1. The publication coincided with a presentation at ASCO 2018, the annual meeting of the American Society of Clinical Oncology in Chicago.

PFS analyses favored the once-weekly treatment in all subgroups except patients with standard-risk cytogenetics, in which PFS was similar with both treatments.

Time to progression was significantly longer in the once-weekly group (12.4 months) than in the twice-weekly group (8.5 months), and significantly more patients in the once-weekly group (62.9%) than in the twice-weekly group (40.8%) achieved overall responses.

Overall survival data were not yet mature at the interim analysis. At 12 months, survival rates were 76.6% for the once-weekly group and 71.9% for the twice-weekly group.

The incidence of treatment-emergent grade 3 or higher adverse events was similar with once-weekly treatment (68%) and twice-weekly treatment (62%), as was the incidence of treatment-emergent serious adverse events (43% vs. 41%, respectively).

Serious adverse events related to treatment, however, were reported by more patients in the once-weekly group (21%) than in the twice-weekly group (13%).

"These results provide encouragement to investigate once-weekly carfilzomib at 70 mg/m2 in combination with lenalidomide and dexamethasone in future studies," the researchers conclude.

"Based on ENDEAVOR, the current standard dose for twice weekly carfilzomib with dexamethasone is 56 mg/m2, and it remains to be established how this compares with a dose of 70 mg/m2 once a week," write Dr. Holger W. Auner from Imperial College London and Dr. Kwee L. Yong from University College London in an accompanying editorial.

"Further studies are therefore still needed to establish standard carfilzomib doses and administration schedules for combinations therapies for relapsed multiple myeloma," they conclude. "Meanwhile, physicians will need to rely on careful scrutiny of adverse event profiles in patient subgroups, as well as reports of real-world experience. Undoubtedly, though, the results of the A.R.R.O.W. study usher in a new era in carfilzomib treatment."

Dr. Moreau did not respond to a request for comments.

Amgen, Inc., which markets carfilzomib as Kyprolis, funded the study, employed two of the authors and had various ties to the rest, including the editorialists.

SOURCE: https://bit.ly/2JJ9H4Y and https://bit.ly/2sP9q6A

Lancet Oncol 2018.



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