Once-Weekly Carfilzomib Superior to Twice-Weekly Regimen in Relapsed/Refractory Multiple Myeloma

The interim analysis of the phase 3 A.R.R.O.W. trial found that once-weekly carfilzomib at 70 mg/m2 had superior progression-free survival and overall response rates compared with twice-weekly carfilzomib at 27 mg/m2.

Patients with relapsed or refractory multiple myeloma who were treated with 70 mg/m2 once-weekly carfilzomib (Kyprolis, Amgen) with once-weekly dexamethasone achieved superior progression-free survival (PFS) and overall response rates (ORR) compared with twice-weekly carfilzomib at 27 mg/m2 with twice-weekly dexamethasone.

The interim results of the phase 3 A.R.R.O.W. trial were presented at the American Society of Clinical Oncology Annual Meeting in Chicago, Illinois, and simultaneously published in The Lancet Oncology. The drug is currently approved by the FDA for the treatment of relapsed or refractory multiple myeloma at 27 mg/m2.

The study recruited 578 patients from 118 sites who had previously been treated with 2 or 3 treatments. They were randomly assigned 1:1 to receive carfilzomib either once a week (70 mg/m2) or twice a week (27 mg/m2). The researchers sought to compare PFS between the 2 groups.

The once-weekly group received carfilzomib on days 1, 8, and 15 of all cycles. The twice-weekly group received carfilzomib on days 1, 2, 8, 9, 15, and 16. Treatment continued until disease progression, unacceptable toxicity, or withdrawal of consent.

The investigators found that patients on the once-weekly treatment had a higher median PFS (11.2 months) compared with the twice-weekly group (7.6 months). There was a slightly higher incidence of grade 3 or higher adverse events in the once-weekly group (68%) compared with the twice-weekly group (62%), but, overall, safety was comparable between the 2 groups. According to the study, 95% of patients in the once-weekly group experienced any grade adverse event compared with 97% in the twice-weekly group. Common adverse events included anemia, pyrexia, diarrhea, fatigue, insomnia, and hypertension.

"Through our patient-centric approach, we strive to improve outcomes and experience for patients with multiple myeloma," said David M. Reese, MD, senior vice president of Translational Sciences and Oncology at Amgen. "Results from A.R.R.O.W. show patients can benefit from receiving Kyprolis with a once-weekly dosing schedule. We have engaged with regulatory agencies and look forward to filing as soon as possible to potentially expand our label to include this option for patients with relapsed and refractory multiple myeloma."

The researchers also performed an efficacy analysis in the intention-to-treat population (consisting of randomly assigned patients; 240 in the once-weekly group and 238 in the twice-weekly group). Significantly more patients in the once-weekly group (62.9%) achieved an overall response compared with 40.8% in the twice-weekly group.

Since this was an interim analysis, overall survival data were not yet mature, and the patients will continue to be followed for mortality. However, overall survival at 12 months was 76.6% in the once-weekly group and 71.9% in the twice-weekly group.

The authors wrote that the results of the interim analysis were encouraging, and that once-weekly carfilzomib in combination with lenalidomide and dexamethasone should be investigated in future studies.

“Overall, in comparison with twice-weekly carfilzomib treatment, once-weekly carfilzomib treatment showed a favorable benefit—risk profile with a more convenient dosing regimen for the treatment of patients with relapsed and refractory multiple myeloma,” the authors concluded.

Reference

Moreau P, Mateos M-V, Berenson JR, et al. Once weekly versus twice weekly carfilzomib dosing in patients with relapsed and refractory multiple myeloma (A.R.R.O.W.): interim analysis results of a randomised, phase 3 study. [published online June 1, 2018]. Lancet. doi: 10.1016/S1470-2045(18)30354-1.