Phase 1/2 study of weekly carfilzomib, cyclophosphamide, dexamethasone in newly diagnosed transplant-ineligible myeloma

S Bringhen, M D'Agostino, L De Paoli, V Montefusco, A M Liberati, P Galieni, S Grammatico, V E Muccio, F Esma, C De Angelis, P Musto, S Ballanti, M Offidani, M T Petrucci, G Gaidano, P Corradini, A Palumbo, P Sonneveld, M Boccadoro

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Abstract

This multicentre, open-label phase 1/2 trial determined safety and efficacy of weekly carfilzomib plus cyclophosphamide-dexamethasone (wKCyd) in newly diagnosed multiple myeloma (NDMM) patients aged ⩾65 years or transplant ineligible. Patients received wKCyd for up to nine 28-day cycles, followed by maintenance with carfilzomib until progression/intolerance. The phase 1 portion used a 3+3 dose-escalation scheme to determine the maximum tolerated dose of weekly carfilzomib: 12 patients received wKCyd with carfilzomib doses of 45, 56 and 70 mg/m2. The recommended phase 2 dose was established at 70 mg/m2 and 54 patients (phase 1 and 2) received weekly carfilzomib 70 mg/m2: 85% of them achieved ⩾partial response (PR), 66% ⩾very good PR, 30%⩾near-complete response (CR) and 15% CR. Responses improved in 40 patients who started maintenance: 98% achieved ⩾PR, including 29% CR and 10% stringent CR. After a median follow-up of 18 months, the 2-year progression-free survival and overall survival rates were 53.2% and 81%, respectively. The most frequent grade 3-5 toxicities were neutropenia (22%) and cardiopulmonary adverse events (9%). This is the first study of weekly carfilzomib plus an alkylating agent in elderly patients with NDMM. wKCyd was effective, with an acceptable risk/benefit ratio, and thus can be a valid option in this setting.Leukemia advance online publication, 22 December 2017; doi:10.1038/leu.2017.327.

Original languageEnglish
JournalLeukemia
DOIs
Publication statusE-pub ahead of print - Nov 16 2017

Keywords

  • Journal Article

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    Bringhen, S., D'Agostino, M., De Paoli, L., Montefusco, V., Liberati, A. M., Galieni, P., Grammatico, S., Muccio, V. E., Esma, F., De Angelis, C., Musto, P., Ballanti, S., Offidani, M., Petrucci, M. T., Gaidano, G., Corradini, P., Palumbo, A., Sonneveld, P., & Boccadoro, M. (2017). Phase 1/2 study of weekly carfilzomib, cyclophosphamide, dexamethasone in newly diagnosed transplant-ineligible myeloma. Leukemia. https://doi.org/10.1038/leu.2017.327