Triplets based on lenalidomide plus dexamethasone (Rd) combinations have become the new standard of care for early relapse and refractory multiple myeloma (RRMM). Carfilzomib is a novel selective proteasome inhibitor (PI) with high efficacy in RRMM.
The ASPIRE phase 3 trial showed the superiority of carfilzomib-based triplet (KRd compared to Rd) but little is known about safety and efficacy of KRd outside a clinical trial context.
In 12 Sicilian Centers belonging to the Sicilian Myeloma Network, from November 2016 to June 2018, 130 consecutive RRMM patients (previous lines 1-10) have received KRd regimen, according to the ASPIRE schedule. Lenalidomide dosage was reduced in patients with a low count of platelet and/or renal failure according to manufacturer guidelines.
Median age was 62 years (range 33-86), most patients were males (56%). About half of the patients included in the survey were refractory to previous treatment (52%).
Median number of administered cycles was 14 (1-31), with a mean duration of treatment of 14 months; 23 (18%) received more than 18 cycles and are still on treatment. Granulocyte growth factors and/or erythropoietin were used to prevent or treat hematological toxicities.
The overall response rate was 61% (79 patients); 22 patients (17%) achieved a complete response (CR), 24 (18%) patients very good partial response (VGPR), 33 (25%) patients achieved partial response (PR). After a median follow up of 18 months, progression occurred in 31 patients, including 14 (11%) who did not achieved any response.
Overall median PFS was 21.7 months, median OS was not reached. In the attempt to identify patients that could obtain the most advantage by KRd treatment, univariate analysis of PFS and OS showed that previous exposure to more than two lines of treatment, including previous exposure to lenalidomide or pomalidomide was associated to shorter median PFS and OS (Table 1). In addition, we found that patients who received the full-dosage of carfilzomib in the first two cycles (310 mg/m2) had a better outcome: median PFS 22.9 vs 14.9 months (p = 0.036), median OS unreached vs 19.1 months (p = 0.029).
Thalidomide, previous autologous Bone Marrow Transplantation (BMT), sex, age, type of relapse (biochemical versus aggressive), disease status (relapsed versus relapsed/refractory) did not affect neither PFS and OS of patients treated with KRd. However, multivariate analysis showed that only creatinine clearance <30 ml/min was significantly associated to reduced PFS and OS (Table 1).
In this retrospective, multicenter, real-life series, about half RRMM patients treated with KRd obtained at least VGPR with an acceptable safety profile. It is reasonable that approaches aimed at maintaining a high cumulative dose, such as continuing therapy in responding patients and/or proactive adverse events management, could influence efficacy.