Once-weekly Versus Twice-weekly Carfilzomib in Combination With Dexamethasone in Adults With Relapsed and Refractory Multiple Myeloma

Summary

The purpose of the study is to compare the progression-free survival (PFS) of once-weekly carfilzomib dosing in combination with dexamethasone to twice-weekly carfilzomib dosing in combination with dexamethasone in adults with relapsed and refractory multiple myeloma, previously treated with bortezomib and an immunomodulatory agent (IMiD).

Timeline

Start

2015-09-09

Primary completion

2017-06-15

Completion

2019-01-07

Outcome

Met primary endpoint

release “The A.R.R.O.W. trial showed that when given once per week at the higher dose of 70 mg/m 2 with dexamethasone, KYPROLIS achieved superior progression-free survival” amgen.com ↗

release “Patients in the trial treated with once-weekly Kyprolis achieved a statistically significant 3.6 month improvement in progression-free survival (PFS) compared with the twice-weekly regimen” ligand.com ↗

Publications

• Background Moreau P, Mateos MV, Berenson JR, Weisel K, Lazzaro A, Song K, Dimopoulos MA, Huang M, Zahlten-Kumeli A, Stewart AK. 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. Lancet Oncol. 2018 Jul;19(7):953-964. doi: 10.1016/S1470-2045(18)30354-1. Epub 2018 Jun 1.
• Background Facon T, Niesvizky R, Mateos MV, Siegel D, Rosenbaum C, Bringhen S, Weisel K, Ho PJ, Ludwig H, Kumar S, Wang K, Obreja M, Yang Z, Klippel Z, Mezzi K, Goldrick A, Tekle C, Dimopoulos MA. Efficacy and safety of carfilzomib-based regimens in frail patients with relapsed and/or refractory multiple myeloma. Blood Adv. 2020 Nov 10;4(21):5449-5459. doi: 10.1182/bloodadvances.2020001965.
• Background Dimopoulos MA, Niesvizky R, Weisel K, Siegel DS, Hajek R, Mateos MV, Cavo M, Huang M, Zahlten-Kumeli A, Moreau P. Once- versus twice-weekly carfilzomib in relapsed and refractory multiple myeloma by select patient characteristics: phase 3 A.R.R.O.W. study subgroup analysis. Blood Cancer J. 2020 Mar 9;10(3):35. doi: 10.1038/s41408-020-0300-y.
• Background Moreau P, Stewart KA, Dimopoulos M, Siegel D, Facon T, Berenson J, Raje N, Berdeja JG, Orlowski RZ, Yang H, Ma H, Klippel Z, Zahlten-Kumeli A, Mezzi K, Iskander K, Mateos MV. Once-weekly (70 mg/m2 ) vs twice-weekly (56 mg/m2 ) dosing of carfilzomib in patients with relapsed or refractory multiple myeloma: A post hoc analysis of the ENDEAVOR, A.R.R.O.W., and CHAMPION-1 trials. Cancer Med. 2020 May;9(9):2989-2996. doi: 10.1002/cam4.2945. Epub 2020 Feb 28.
• Background Moreau P, Kumar S, Boccia R, Iida S, Goldschmidt H, Cocks K, Trigg A, Zahlten-Kumeli A, Yucel E, Panjabi SS, Dimopoulos M. Convenience, satisfaction, health-related quality of life of once-weekly 70 mg/m2 vs. twice-weekly 27 mg/m2 carfilzomib (randomized A.R.R.O.W. study). Leukemia. 2019 Dec;33(12):2934-2946. doi: 10.1038/s41375-019-0480-2. Epub 2019 May 15.
• Background Kumar SK, Majer I, Panjabi S, Medhekar R, Campioni M, Dimopoulos MA. Cost-effectiveness of once weekly carfilzomib 70 mg/m2 plus dexamethasone in patients with relapsed and refractory multiple myeloma in the United States. Expert Rev Hematol. 2020 Jun;13(6):687-696. doi: 10.1080/17474086.2020.1746639. Epub 2020 Apr 6.
• Dimopoulos MA, Moreau P, Iida S, Huang SY, Takezako N, Chng WJ, Zahlten-Kumeli A, Sersch MA, Li J, Huang M, Lee JH. Outcomes for Asian patients with multiple myeloma receiving once- or twice-weekly carfilzomib-based therapy: a subgroup analysis of the randomized phase 3 ENDEAVOR and A.R.R.O.W. Trials. Int J Hematol. 2019 Oct;110(4):466-473. doi: 10.1007/s12185-019-02704-z. Epub 2019 Aug 6.

Drugs

Evaluation	Drug	Modality	Dose	Route
Subject	Carfilzomib	Other / unclassified	27 mg/m2	Intravenous
Subject	Carfilzomib	Other / unclassified	70 mg/m2	Intravenous
Background	Dexamethasone	Small molecule	40 mg	Intravenous

Indications