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Ferrata Storti Foundation
Haematologica 2019 Volume 104(8):1640-1647
Plasma Cell Disorders
Once-weekly versus twice-weekly carfilzomib in patients with newly diagnosed multiple myeloma: a pooled analysis of two phase I/II studies
Sara Bringhen,1 Roberto Mina,1 Maria Teresa Petrucci,2 Gianluca Gaidano,3 Stelvio Ballanti,4 Pellegrino Musto,5 Massimo Offidani,6 Stefano Spada,1 Giulia Benevolo,7 Elena Ponticelli,1 Piero Galieni,8 Michele Cavo,9 Tommaso Caravita Di Toritto,10* Francesco Di Raimondo,11
Vittorio Montefusco,12 Antonio Palumbo,1** Mario Boccadoro1 and Alessandra Larocca1
1Myeloma Unit, Division of Hematology, University of Torino, Azienda Ospedaliero- Universitaria Città della Salute e della Scienza di Torino, Torino; 2Division of Hematology, Department of Cellular Biotechnologies and Hematology, Sapienza University of Rome, Rome; 3Division of Hematology, Department of Translational Medicine, Università del Piemonte Orientale, Novara; 4Sezione di Ematologia e Immunologia Clinica, Ospedale Santa Maria della Misericordia di Perugia, Perugia; 5Unit of Haematology and Stem Cell Transplantation, IRCCS-CROB, Referral Cancer Center of Basilicata, Rionero in Vulture; 6Clinica di Ematologia, AOU Ospedali Riuniti di Ancona, Ancona; 7Hematology, Città della Salute e della Scienza, Turin; 8Division of Hematology, Ospedale “C. e G. Mazzoni”, ASUR Marche-AV5, Ascoli Piceno; 9"Seràgnoli" Institute of Hematology, Bologna University School of Medicine, Bologna; 10UOC Ematologia, Ospedale S. Eugenio, ASLRM2, Rome; 11Division of Hematology, AOU Policlinico-OVE, University of Catania, Catania and 12Hematology Department, Fondazione IRCCS Istituto Nazionale Tumori, Milano, Italy
*currently employed at UOSD Ematologia, P.O. S. Spirito e Nuovo Regina Margherita ASLRM1, Rome; **currently employed at Takeda Pharmaceuticals International, Switzerland
ABSTRACT
Twice-weekly carfilzomib is approved at 27 and 56 mg/m2 to treat relapsed multiple myeloma patients. In the phase III study ARROW,
2
once-weekly 70 mg/m carfilzomib prolonged the median progres-
sion-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 trans- plant-ineligible patients with newly diagnosed multiple myeloma were ana- lyzed (once-weekly, n=63; twice-weekly, n=58). We found no significant dif- ference 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. Once- weekly 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 sched- ule. The trials are registered at clinicaltrials.gov identifiers: 01857115 (IST-CAR- 561) and 01346787 (IST-CAR-506).
Correspondence:
SARA BRINGHEN
sarabringhen@yahoo.com
Received: October 4, 2018. Accepted: February 7, 2019. Pre-published: February 7, 2019.
doi:10.3324/haematol.2018.208272
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