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Once-Weekly Carfilzomib Safe, Effective in All Age Groups of Patients With RRMM

Laura Joszt
Patients of all ages see benefits with once-weekly carfilzomib compared with a twice-weekly dose, according to an analysis of the phase 3 A.R.R.O.W. trial.
The interim analysis1 of the phase 3 A.R.R.O.W. trial showed once-weekly carfilzomib (Kyprolis) improved progression-free survival (PFS) and the overall response rate (ORR) compared with the twice-weekly dose, and a new abstract delved deeper into subgroups to analyze if the findings were the same. The abstract was presented at the 60th American Society of Hematology Annual Meeting and Exposition.

The study2 analyzed whether age had any impact on the efficacy and safety of the once-weekly dose versus the twice-weekly dose in patients with relapsed/refractory multiple myeloma (RRMM). The A.R.R.O.W. study included 478 patients with 208 patients younger than 65, 270 patients 65 or older, 400 patients younger than 75 years, and 78 patients 75 and older.

In the study, patients receiving once-weekly carfilzomib received the treatment for a longer duration than the twice-weekly group. In all age groups, median PFS was longer: 12.2 months versus 5.6 months in the under-65 group; 11.2 months versus 8.7 months in the 65 and older group; 11.1 months versus 7.4 months in the under-75 group; and 12.2 months versus 9.5 months in the 75 and older group.

In addition, the ORR outcomes were better for all age groups taking the once-weekly dose compared with the twice-weekly dose. ORR for patients under 65 was 64.4% compared with 34.6%; for patients age 65 and older, 61.8% versus 45.5%; for patients younger than 75 years, 62.4% versus 38.3%; and in the 75 and older group, 65.2% versus 56.3%.

The safety profile between the 2 doses was similar. In the under-65 age group, 92.2% receiving the once-weekly dose and 97.1% receiving the twice-weekly dose experienced at least 1 treatment-emergent adverse event (AE) of any grade. The other age groups were even closer:
  • 97.1% in the once weekly and 97.7% in the twice-weekly groups of those 65 and older
  • 94.3% in the once weekly and 97.1% in the twice-weekly groups of those 75 and younger
  • 100% for both doses in the 75 and older group.
The authors determined that patients younger than age 65 “experienced the maximum PFS benefit” with once-weekly carfilzomib and that there was also a benefit for patients older than age 75.

“Furthermore, the safety profile associated with once weekly [carfilzomib] was comparable to that of twice weekly [carfilzomib] across age groups, suggesting that once weekly carfilzomib dosing at 70 mg/m2 is an effective and convenient regimen for [patients] with RRMM irrespective of age,” the authors concluded.

References
  1. 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.
  2. Dimopoulos MA, Niesvizky R, Moreau P, et al. Once weekly versus twice weekly carfilzomib dosing in patients with relapsed and refractory multiple myeloma (A.R.R.O.W.): efficacy and safety analyzed by age group. Presented at the 60th American Society of Hematology Annual Meeting & Exposition; December 2, 2018. San Diego, CA. Abstract 3277.


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