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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)., (Copyright© 2019 Ferrata Storti Foundation.)

Lenalidomide plus dexamethasone is effective in the treatment of multiple myeloma (MM) but is associated with an increased risk of venous thromboembolism (VTE). This prospective, open-label, randomized substudy of a phase 3 trial compared the efficacy and safety of thromboprophylaxis with low-dose aspirin (ASA) or low-molecular-weight heparin (LMWH) in patients with newly diagnosed MM, treated with lenalidomide and low-dose dexamethasone induction and melphalan-prednisone-lenalidomide consolidation. Overall, 342 patients who did not have clinical indications or contraindications to antiplatelet or anticoagulant therapy were randomly assigned to receive ASA 100 mg/d (n = 176) or LMWH enoxaparin 40 mg/d (n = 166). The incidence of VTE was 2.27% in the ASA group and 1.20% in the LMWH group. Compared with LMWH, the absolute difference in the proportion of VTE was 1.07% (95% confidence interval, -1.69-3.83; P = .452) in the ASA group. Pulmonary embolism was observed in 1.70% of patients in the ASA group and none in the LMWH group. No arterial thrombosis, acute cardiovascular events, or sudden deaths were reported. No major hemorrhagic complications were reported. In previously untreated patients with MM receiving lenalidomide with a low thromboembolic risk, ASA could be an effective and less-expensive alternative to LMWH thromboprophylaxis.