Once-weekly versus twice-weekly carfilzomib in patients with newly diagnosed multiple myeloma: a pooled analysis of two phase 1/2 studies

Twice-weekly carfilzomib is approved at 27 and 56 mg/m 2 to treat relapsed multiple myeloma patients. In the phase 3 study A.R.R.O.W., 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 1/2 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=63; twice-weekly=58). We found no significant difference in median progression-free survival (35.7 months [95% CI 23.7-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% [58%-89%] vs 73% [59%-90%]; HR: 0.82; p=0.71) were similar in the once- versus twice-weekly carfilzomib. The rate of grade 3-5 hematological (24% vs 30%; p=0.82) and non-hematological adverse events (38% vs 41%; p=0.83) 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 with ClinicalTrials.gov, (identification numbers NCT01857115 for IST-CAR-561 and NCT01346787 for IST-CAR-506).