PF644 CARFILZOMIB, LENALIDOMIDE AND DEXAMETHASONE IN RELAPSED/REFRACTORY MULTIPLE MYELOMA PATIENTS: THE REAL LIFE EXPERIENCE OF RETE EMATOLOGICA PUGLIESE (REP)
Authors: Mele A. , Prete E. , De Risi C. , Greco G. , Citiso S. , Cascavilla N. , Falcone A.P. , Sanpaolo G. , Pastore D. , Mele G. , Giannotta A. , Di Renzo N. , Vergine C. , Reddiconto G. , Mazza P. , Palazzo G. , Sabatelli S. , Tarantini G. , Germano C. , Miccolis R. , Specchia G. , Curci P. , Rizzi R. , Guarini A. , Capalbo S. , Morciano M.R. , Greco A. , De Francesco R. , Sibilla S. , Pavone V. 
Published: June 2019

Background:Carfilzomib, lenalidomide and dexamethasone (KRd) has been approved for the treatment of relapsed and refractory multiple myeloma (RRMM) based on ASPIRE clinical trial. However, its effectiveness and safety profile in real clinical practice should be further assessed.Aims:We retrospectively evaluated 120 consecutive RRMM patients treated with KRd, in 9 hematology departments of Rete Ematologica Pugliese (REP), with the aim to evaluate the efficacy and safety with KRd treatment in a real world setting.Methods:Between December of 2015 and August 2018,120 RRMM patients were analyzed.The patients’ baseline characteristics are presented in Table 1. Median patient's age was 66 years and 41 patients(34%) were older than 70 years. The median number of previous treatment lines was 1 (range 1–11). The 94% of the patients had been already treated with bortezomib‐based regimens and 33% with both lenalidomide‐ and bortezomib‐based regimens. Moreover, half of the patients (52%) had a previous autologous stem cell transplant. The median time from the diagnosis to start of treatment with KRd was 40 months (range 5–295) and 30 patients were treated with KRd early (≤18 months from diagnosis).Disease status at the start of treatment with KRd was refractory in 33 patients(29%) and 13 patients(12%) were refractory to lenalidomide. Twenty‐four patients(21%) were refractory at last therapy before KRd enrollment.Results:The overall response rate (ORR) was 84%(n = 93),with 23%(25) complete response (CR) and 50%(55) very good partial response(VGPR).The median duration of response was 12,9 months (range, 3,33–27,7). ORR was higher in patients relapsed after a previous autologous transplant (ASCT;56% vs 37% in those relapsed without prior ASCT;p 0,05).Patients treated in late relapse had a better ORR (44%) vs those in early relapse (19%; p 0,02). After a median follow‐up of 13,4 months, median PFS was not reached (NR) and 2y‐PFS was 61%, Figure 1. PFS was longer in responding patients (achieving at least PR) to those with less than PR (median PFS NR vs 4,9 months;p 0,0001).Median PFS in patients relapsed after a prior ASCT was NR vs 20 months in those without prior ASCT, (p 0,002).Patients achieving ASCT after KRD had a better PFS in confront to those without ASCT (median NR vs 9 months, p 0,001).Several baseline patient characteristics, such as the III ISS scoring, older age, prior exposure to lenalidomide and early relapse were found to negatively impact PFS.Twenty‐eight patients(24%) performed 4 KRd cycles as bridge treatment to ASCT. The 64% of patients reached a VGPR and 67% received ASCT, with 9 upgraded from VGPR to complete response (CR) after ASCT.The treatment discontinuation rate due to adverse events (AEs) was 13%, most commonly related to lenalidomide(8%). KRd dose reduction was necessary in 11% of patients (2,5% for carfilzomib and 8% for lenalidomide).The most frequent AE was neutropenia(43%) and anemia (41%). Infections occurred in 10% of patients.Adverse Cardiovascular toxicity (Atrial fibrillation and pulmonary hypertension)occurred in 8% of patients.Summary/Conclusion:Our analysis confirmed that KRd is effective in RRMM patients. It is well tolerated and applicable to the majority of patients outside clinical trials. A longer PFS was shown in patients achieving at least a partial response (PR), relapsing after previous ASCT and in those with the possibility to perform ASCT after KRd treatment. Accordingly,KRd should be used as an optimal bridge regimen to ASCT. Previous ASCT should not hamper the option for KRd therapy.image