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Multiple myeloma, gammopathies

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

Leukemia volume 32, pages 979–985 (2018)Cite this article

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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.

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Acknowledgements

We thank all patients who took part in the study; the nurses Montanaro Vincenza and Puccio Loredana, and Federica Leotta, Marta Santoro and Giorgio Schirripa from the coordinating site in Torino for their assistance with the study.

Author contributions

All authors participated in the interpretation of data, and reviewed and approved all drafts of the manuscript, including the decision to submit for publication. SB, LDP, PS and MB contributed to the study design. SB conducted the data analyses. SB and MB wrote the first draft of the manuscript. All authors provided patients and/or study materials.

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  1. A Palumbo: This author is currently an employee of Takeda.

Authors and Affiliations

  1. Division of Hematology, Myeloma Unit, University of Torino, Azienda Ospedaliero-Universitaria Città della Salute e della Scienza di Torino, Torino, Italy

    S Bringhen, M D'Agostino, V E Muccio, F Esma, A Palumbo & M Boccadoro

  2. Division of Hematology, Department of Translational Medicine, Università del Piemonte Orientale and Azienda Ospedaliero-Universitaria Maggiore della Carità, Novara, Italy

    L De Paoli & G Gaidano

  3. Hematology Departement, Fondazione IRCCS Istituto Nazionale Tumori, Milano, Italy

    V Montefusco

  4. Department of Oncohematology, Hospital S. Maria, Terni, Italy

    A M Liberati & C De Angelis

  5. UOC di Ematologia e Terapia Cellulare, Ospedale C. e G. Mazzoni, Ascoli Piceno, Italy

    P Galieni

  6. Department of Cellular Biotechnologies and Hematology, Hematology, Sapienza University of Rome, Rome, Italy

    S Grammatico & M T Petrucci

  7. Scientific Direction, IRCCS-CROB, Referral Cancer Center of Basilicata, Rionero in Vulture (Pz), Italy,

    P Musto

  8. Sezione di Ematologia e Immunologia Clinica, Ospedale Santa Maria della Misericordia di Perugia, Perugia, Italy

    S Ballanti

  9. Clinica di Ematologia, AOU Ospedali Riuniti di Ancona, Ancona, Italy

    M Offidani

  10. Department of Oncology-Hematology, University of Milano, Italy

    P Corradini

  11. Department of Hematology, Erasmus Medical Center, Rotterdam, The Netherlands

    P Sonneveld

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  1. S Bringhen
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Corresponding author

Correspondence to S Bringhen.

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Competing interests

SB has received honoraria from BMS, Celgene and Janssen-Cilag, and served on the advisory board for Amgen, Mundipharma and Karyopharm. LDP has received honoraria from Amgen, Celgene, Abbvie and Janssen. VM has received speaker’s bureau and advisory board for Amgen. PG has served on the advisory board for Takeda. MO has received honoraria from Celgene. MTP has received honoraraia from Celgene, Janssen-Cilag, BMS, Takeda and Amgen. GG has served on the advisory board for Amgen, Janssen, Gilead, Abbvie, Morphosys and Roche. AP is currently a Takeda employee. PS has received research support from Amgen, Celgene, Janssen and Karyopharm, and honoraria from Amgen, Celgene, Janssen, Karyopharm and BMS. MB has received honoraria from Sanofi, Celgene, Amgen, Janssen, Novartis, Abbivie and BMS, and research funding from Celgene, Janssen, Amgen, BMS, Mundipharma, Novartis and Sanofi.

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Bringhen, S., D'Agostino, M., De Paoli, L. et al. Phase 1/2 study of weekly carfilzomib, cyclophosphamide, dexamethasone in newly diagnosed transplant-ineligible myeloma. Leukemia 32, 979–985 (2018). https://doi.org/10.1038/leu.2017.327

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