Carfilzomib combined with lenalidomide and dexamethasone (KRd) as salvage therapy for multiple myeloma patients: Italian, multicenter, retrospective clinical experience with 600 cases outside of controlled clinical trials

Abstract

In combination with lenalidomide and dexamethasone (KRd), Carfilzomib has been approved for the treatment of relapsed and refractory multiple myeloma (RRMM) on ASPIRE trial. Efficacy and safety of the triplet are stillthe object of investigationby many groupstoconfirmASPIRE results in the setting of RRMM treatedin real-life who don’t meet trial restrictive inclusion criteria.Therefore, we report a retrospective multicenter analysis of 600 RRMM patients treated with KRd between December 2015 and December 2018. The medianage was 64 years (range 33-85),and the median number of previous therapies was 2 (range 1-11). After a median of 11 KRd cycles, the ORR was 79.9%. The median PFS was 22 months,and the 2-year probability of PFS was 47.6%. Creatinine clearance<30 mL/min, >1line of previous therapy, and high-risk FISH were all associated with a poor prognosis in multivariate analysis.The median OS was 34.8 months; the 2-year probability of OS was 63.5%.At multivariate analysis,creatinine clearance<30 ml/min, >1 line of previous therapy,and high-risk FISH were significantly associated with poor prognosis. After a median follow-up of 16 months (range 1-50),259 withdrew from therapy. The main discontinuation reasonwas progressive disease (81.8%). Seventy-four patients (12.3%) discontinued therapy for toxicity. The most frequent side effects were hematological (anemia 49.3%, neutropenia 42.7%, thrombocytopenia 42.5%) and cardiovascular (hypertension 14.5%, heart failure 2.5%, arrhythmias 3.6%).Our studyconfirmsthe safety and efficacy of KRd in the real-life setting of RRMM patients and encourages its use in clinical practice.