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Higher, Less Frequent Dose of Multiple Myeloma Therapy Improves PFS


A recent study confirmed that administering a higher dosage once-weekly of a common therapy for relapsed or refractory multiple myeloma improves progression-free survival (PFS) by 3.6 months, compared with twice-weekly administration of a lower dosage.

In the phase III trial, researchers sampled 478 patients with relapsed or refractory multiple myeloma and randomly assigned them to either of two treatment arms: carfilzomib (70 mg/m2) once weekly or carfilzomib (27 mg/m2) twice weekly. Patients in both treatment arms were also administered dexamethasone.

Enrollment criteria for the study included at least two, but no more than three, prior treatments that included bortezomib and an immunomodulatory agent. The primary outcome was PFS, while secondary outcomes included overall response rate, overall survival, safety, and tolerability.

The study (ARROW) was conducted and supported by Amgen ( Identifier: NCT02412878).

Results of the study showed that patients in the carfilzomib once weekly arm had a significantly superior PFS compared with those receiving the twice weekly dosage (11.2 months vs 7.6 months, respectively; HR, 0.69; 95% CI, 0.54-0.88). The variables in dosage amounts and administration schedules accounted for a 3.6-month advantage for patients receiving a higher dosage once-weekly.


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Additionally, the overall safety profile of the once-weekly regimen was comparable to that of the twice-weekly regimen. Among the most frequently reported treatment-related adverse events (at least 20%) in either treatment arm were anemia, diarrhea, fatigue, hypertension, insomnia, and pyrexia.

"[Carfilzomib] has been demonstrated to be the most effective proteosome inhibitor available to patients with multiple myeloma," said Sean E Harper, MD, executive vice president of Research and Development, Amgen, in a press release (October 23, 2017). "We are encouraged by the efficacy and safety profile of [carfilzomib] and dexamethasone administered once-weekly in the ARROW study."—Zachary Bessette