Continous or fixedcarfilzomib, lenalidomide and dexamethasone (krd) for relapsed-refractory multiple myeloma: long-term follow-up from a multicenter, retrospective real-life surveyfrom European myeloma network (emn) Italy.

Based on the results of the ASPIRE trial, the KRd regimen (carfilzomib, lenalidomide and dexamethasone) has been approved in Italy for relapsed/refractory multiple myeloma (RRMM) patients since 2016. The published KRd schedule indicates this combination for 18 cycles, followed by continuous Rd until progression. However, in Italy, there are no limits to the number of KRd cycles, fully refunded based on negotiation with the Italian regulatory agency, and in some centers this combination has been used continuously, beyond the 18th cycle (continuous KRd, cKRd). To evaluate and compare safety and efficacy of both continuous and fixed KRd, we retrospectively collected real-world data from 356 patients treated in 20 EMN (European Myeloma Network) Italian centers from October 2016 to September 2023 and we patients treated with cKRd with those treated with the ASPIRE schedule. After a median follow-up of 48.59 months (CI 27.24-61.24), the overall response rate (ORR) of the entire series was 83% with 35% of complete responses(CR). The mPFS was 23.1 months (CI 20.11-28.62) and mOS was 62.85 months (CI 53.75-70.34), longer than the mOS of the ASPIRE study (48.3 months). The landmark analysis of the cKRd population shows non-significant benefit both in terms of PFS and OS compared to patients where the administration of KRd was stopped at the 18th cycle as in the ASPIRE trial, to note, in the cKRd group patients had a more aggressive disease based on ISS and R-ISS stage. Therefore, although we did not observe additional toxicities, our retrospective analysis, while confirming the validity of the KRd regimen in RRMM, does not indicate any general advantage in keeping the administration of carfilzomib beyond the ASPIRE schedule.