Real-World Data in Relapsed Refractory Myeloma Patients Treated with Carfilzomib, a Multicenter Turkish Experience

Introduction: Carfilzomib is a potent and irreversible inhibitor of proteasome which exerts clinically significant anti-myeloma effect. Randomized phase 2 and 3 studies have validated carfilzomib as an effective therapy in relapsed or refractory myeloma setting.

In our country, Carfilzomib has recently gained approval in relapsed refractory setting in patients who were both refractory to a proteasome inhibitor and an immunomodulatory drug (imid). Before this approval we were able to use carfilzomib as a single agent or as part of a combination approach via approval of health authority. Here we present our retrospective, multicenter, real life experience among patients with relapsed refractory myeloma and treated with carfilzomib.

Methods: 152 heavily pre-treated patients from 15 centers were retrospectively evaluated and the data among the use of carfilzomib, its efficacy and safety were analyzed.

Results: Median age of the patients included in the study was 69 (43-86) with a male ratio of 56.6%. ISS groups at diagnosis were as follows, stage 1 22.4%, stage 2 51.3% and stage 3 26.3%. 14 of 80 patients (17.5%) were classified as high risk myeloma with an either del 17p or t(4,14) FISH positivity. Most of the patients were refractory to at least one proteasome inhibitor (90.8%), at least one one imid (84.2%), or both 75.6%. Only a small number of patients have used carfilzomib with one other immunomodulatory drug (26.3%) and remaining majority used it as a single agent. All patients have received concomitant corticosteroids and were able to receive at least 2 cycles of carfilzomib. Median number of prior therapy line was 4 (3-8). Overall response rate was 40.8% (complete response + very good partial remission rate 13.2% and Partial remission rate 27.6%). Median duration of response was 4.8 months. Median progression free survival was 6 months and median overall survival was 10.4 months after initiation of carfilzomib. Hematological toxicity was the major toxicity which were reported at 61.8 % of patients. Other major toxicities were as follows: combined cardiovascular toxicity (heart failure, pulmonary hypertension, systemic hypertension) 26.3 %, renal toxicity 9.2 %.

Conclusions: Carfilzomib based treatment is efficient in advanced multiple myeloma. Even in a heavily pre-treated real-life patient group, carfilzomib led to a significant response rate. Most important side effects were hematological and cardiovascular.