P652: IMPROVED SURVIVAL OF PATIENTS WITH CHRONIC LYMPHOCYTIC LEUKEMIA BETWEEN 1998-2022, INCLUDING THE ERA OF TARGET THERAPIES WITH BCL2 AND BTK INHIBITORS.

Background: The treatment for Chronic Lymphocytic Leukemia (CLL) has undergone significant changes over the past two decades. Initially, chemotherapy was the primary treatment, it was later replaced by chemo-immunotherapy, and more recently, began the era of target therapies. Currently, IWCLL guidelines recommend treatment only for symptomatic patients. Aims: The current study aims to examine the overall survival (OS) of CLL patients who were managed under a “watch and wait” policy, and among patients who received treatment, including novel agents such as BCL2 and BTKI, during the period of 1998-2022. Methods: The data were retrieved from anonymized electronic medical records of members of Maccabi Healthcare Services, the second-largest healthcare organization in Israel, after receiving approval from the institute’s ethical committee. All patients included in this study were diagnosed with CLL based on the IWCLL criteria. Furthermore, only patients for whom we had complete data on clinical, laboratory, and given therapy, were included. Results: A total of 3964 patients with CLL were included. Analysis showed a statistically significant improvement in overall survival for the entire cohort (p=0.0001). Patients with CLL who required therapy were classified into three groups based on the dominant treatment approach for their era: Chemotherapy alone before 2010, therapy with chemotherapy and anti-CD20 between 2010-2017, and survival post-2017, when target therapies became the primary treatment used. The median OS was 4.1 years, 7.5 years and not reached, respectively. The 6-year OS was 40%, 55%, and 69%, respectively, with a p-value of 0.0001, indicating a significant improvement in survival (figure 1). When the analysis was done on the basis of treatment given: the 6-year OS was 85% for patients treated with Venetoclax, 68% for Ibrutinib, 65% for FCR, and 60% for BR or Chlorambucil+ anti-CD20 therapy compared to 35% for patients treated with chlorambucil+/- prednisone. Median Time to the next treatment has been improved from 5.5 years before 2010, to 8.3 between 2010-2017 to not reached after 2017. P=0.0021. The cohort included 2840 patients managed with a watch and wait policy, and never received therapy. For patients diagnosed before 2017, their median OS was 13.1 years. For patients diagnosed after 2017, the 5-year OS was 81%. No improvement in OS was observed in patients who were in watch and wait and were diagnosed between 2010 and 2017 or after 2017. However, a statistically significant improvement in OS was observed for patients diagnosed before 2010 (p-value<0.001). Summary/Conclusion: We found marked improvements in relative survival of the population level, following fundamental changes in first-line therapy of patients diagnosed with CLL. Figure 1: Overall survival of patients with CLL during the last 24 years, divided into 3 eras: before 2010, 2010-2017, and between 2017-2022Keywords: B-CLL