Once-weekly versus twice-weekly carfilzomib in patients with newly diagnosed multiple myeloma: A pooled analysis of two phase i/ii studies

Sara Bringhen, Roberto Mina, Maria Teresa Petrucci, Gianluca Gaidano, Stelvio Ballanti, Pellegrino Musto, Massimo Offidani, Stefano Spada, Giulia Benevolo, Elena Ponticelli, Piero Galieni, Michele Cavo, Tommaso Caravita Di Toritto, Francesco Di Raimondo, Vittorio Montefusco, Antonio Palumbo, Mario Boccadoro, Alessandra Larocca

Research output: Contribution to journalArticle

Abstract

Twice-weekly carfilzomib is approved at 27 and 56 mg/m2 to treat relapsed multiple myeloma patients. In the phase III study ARROW, once-weekly 70 mg/m2 carfilzomib prolonged the median progression-free survival of relapsed multiple myeloma patients in comparison with twice-weekly 27 mg/m2 carfilzomib, without adding significant toxicity. Data were pooled from two phase I/II studies of newly diagnosed multiple myeloma patients who received nine induction cycles of carfilzomib (either 70 mg/m2 once-weekly or 36 mg/m2 twice-weekly), cyclophosphamide and dexamethasone, followed by carfilzomib maintenance. Overall, 121 transplant-ineligible patients with newly diagnosed multiple myeloma were analysed (once-weekly, n=63; twice-weekly, n=58). We found no significant difference in median progression-free survival [35.7 months (95%CI: 23.7-not reached, NR) vs. 35.5 months (95%CI: 24.3-NR); HR: 1.39; P=0.26] and 3-year overall survival [70% [95%CI: 59%-84%) vs. 72% (95%CI: 60%-85%); HR: 1.27; P=0.5] between once-weekly and twice-weekly carfilzomib. From the start of maintenance, 3-year progression-free survival [47% (95%CI: 33%-68%) vs. 51% (95%CI: 38%-70%); HR: 1.04; P=0.92] and overall survival [72% (95%CI: 58%-89%) vs. 73% (95%CI: 59%-90%); HR: 0.82; P=0.71] were similar in the once- versus twice-weekly carfilzomib. The rate of grade 3-5 hematologic (24% vs. 30%; P=0.82) and non-hematologic (38% vs. 41%; P=0.83) adverse events was similar in the two groups. Onceweekly 70 mg/m2 carfilzomib as induction and maintenance therapy for newly diagnosed multiple myeloma patients was as safe and effective as twice-weekly 36 mg/m2 carfilzomib and provided a more convenient schedule. The trials are registered at clinicaltrials.gov identifiers: 01857115 (IST-CAR-561) and 01346787 (IST-CAR-506).

Original languageEnglish
Pages (from-to)1640-1647
Number of pages8
JournalHaematologica
Volume104
Issue number8
DOIs
Publication statusPublished - Jul 31 2019

ASJC Scopus subject areas

  • Hematology

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    Bringhen, S., Mina, R., Petrucci, M. T., Gaidano, G., Ballanti, S., Musto, P., Offidani, M., Spada, S., Benevolo, G., Ponticelli, E., Galieni, P., Cavo, M., Di Toritto, T. C., Di Raimondo, F., Montefusco, V., Palumbo, A., Boccadoro, M., & Larocca, A. (2019). Once-weekly versus twice-weekly carfilzomib in patients with newly diagnosed multiple myeloma: A pooled analysis of two phase i/ii studies. Haematologica, 104(8), 1640-1647. https://doi.org/10.3324/haematol.2018.208272