CLL-477 Historical Trends in the Front-Line Treatment in Patients With Chronic Lymphocytic Leukemia: Experience from a European Center

Abstract

The treatment of chronic lymphocytic leukemia (CLL) has dramatically evolved over the last decade thanks to the introduction of the targeted therapies. Nowadays, international guidelines (ESMO 2021, NCCN 2022) recommend targeted therapies including BTKi and BCL2i combinations as the preferred regimens for the treatment of most treatment naïve CLL patients. To describe pattern changes in the front-line treatment in CLL patients. This is a retrospective, single center, and non-interventional study. We included patients treated in clinical trials and in routine clinical practice. Front-line treatment was classified in three groups: (1) chemotherapy-based regimens, (2) chemoimmunotherapy and (3) targeted therapies (i.e., BTK inhibitors, PI3K inhibitors, or BCL2 inhibitors). We reviewed front-line treatment strategies in CLL patients in our institution. We enrolled in total 780 patients diagnosed with CLL between 1979-2022 from our database. No interventions were made in this study. We analyzed the patterns of treatments in front-line and their impact on survival. After a median of 6.5 years (3.3-11.1) of follow-up, 40.1% (313/780) of patients required treatment. Alkylating agents in monotherapy (chlorambucil) were the most used until 2012, and from that year on, immunochemotherapy with fludarabine and cyclophosphamide with rituximab (FCR). Since 2018, targeted therapies were the most common therapeutic strategy (72%) [BTKi (52%), and BCL2i as monotherapy or in combinations (20%)] versus immunochemotherapy (28%). In an exploratory analysis of survival, after a median of 7.5 years (4.7-11.8) of follow-up, those patients treated with targeted therapies showed a longer progression free survival (OR 0.16; 0.07-0.35; p<0.0001) compared to other therapies, although no differences in overall survival were observed (OR 0.83; 0.45-1.54; p=0.56). In our center, targeted therapies have become the most used treatment in CLL, with BTKi standing out followed by BCL2i, which reflects the historical development and approval of these agents. This study provides useful information for the design of therapeutic strategies for CLL both in the healthcare setting and in clinical trials in our country. No grant funding has been provided for this study.