1. Once-weekly versus twice-weekly carfilzomib in patients with newly diagnosed multiple myeloma: a pooled analysis of two phase I/II studies
- Author
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Maria Teresa Petrucci, Mario Boccadoro, Roberto Mina, Massimo Offidani, Pellegrino Musto, Vittorio Montefusco, Stefano Spada, Elena Ponticelli, Giulia Benevolo, Piero Galieni, Antonio Palumbo, Gianluca Gaidano, Michele Cavo, Sara Bringhen, Tommaso Caravita di Toritto, Francesco Di Raimondo, Stelvio Ballanti, Alessandra Larocca, Bringhen, Sara, Mina, Roberto, Petrucci, Maria Teresa, Gaidano, Gianluca, Ballanti, Stelvio, Musto, Pellegrino, Offidani, Massimo, Spada, Stefano, Benevolo, Giulia, Ponticelli, Elena, Galieni, Piero, Cavo, Michele, Di Toritto, Tommaso Caravita, Di Raimondo, Francesco, Montefusco, Vittorio, Palumbo, Antonio, Boccadoro, Mario, and Larocca, Alessandra
- Subjects
Male ,medicine.medical_specialty ,Cyclophosphamide ,Antineoplastic Agents ,carfilzomib,multiple myeloma ,Gastroenterology ,Article ,Plasma Cell Disorders ,Drug Administration Schedule ,Maintenance Chemotherapy ,chemistry.chemical_compound ,Maintenance therapy ,Internal medicine ,Antineoplastic Combined Chemotherapy Protocols ,Medicine ,Humans ,Adverse effect ,Survival analysis ,Multiple myeloma ,Dexamethasone ,Aged ,Aged, 80 and over ,business.industry ,Induction chemotherapy ,Hematology ,Induction Chemotherapy ,Middle Aged ,medicine.disease ,Prognosis ,Carfilzomib ,Survival Analysis ,Treatment Outcome ,chemistry ,Female ,business ,Multiple Myeloma ,Oligopeptides ,medicine.drug - Abstract
Twice-weekly carfilzomib is approved at 27 and 56 mg/m(2) to treat relapsed multiple myeloma patients. In the phase III study ARROW, once-weekly 70 mg/m 2 carfilzomib prolonged the median progression-free survival of relapsed multiple myeloma patients in comparison with twice-weekly 27 mg/m(2) 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/m(2) once-weekly or 36 mg/m(2) twice-weekly), cyclophosphamide and dexamethasone, followed by carfilzomib maintenance. Overall, 121 transplant-ineligible patients with newly diagnosed multiple myeloma were analyzed (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. Once-weekly 70 mg/m(2) carfilzomib as induction and maintenance therapy for newly diagnosed multiple myeloma patients was as safe and effective as twice-weekly 36 mg/m(2) carfilzomib and provided a more convenient schedule. The trials are registered at clinicaltrials.gov identifiers: 01857115 (IST-CAR-561) and 01346787 (IST-CAR-506).
- Published
- 2019