Survival trends in chronic lymphocytic leukemia before and after BTK inhibitors era: A SEER database analysis

Abstract

Abstract Introduction: Significant advances have been made in the last decade in the treatment of Chronic Lymphocytic Leukemia (CLL). Bruton kinase inhibitors (BTKi) such as Ibrutinib, Acalabrutinib and Zanubrutinib have revolutionized the treatment of CLL by irreversibly binding to BTK, an enzyme crucial for B-cell signaling pathways, and preventing the survival and proliferation of malignant B-cells. Ibrutinib was the first BTKi which was approved in 2016 for newly diagnosed and relapsed disease showing overall and progression-free survival benefit; however, several limitations have been identified, including low complete remission rates, development of resistance, and uncommon substantial toxicities. Further, BTKi must be used until disease progression, which imposes a financial burden on patients and society. Our study investigates survival trends among CLL patients in the pre and post BTKi era using data from the Surveillance, Epidemiology, and End Results (SEER) database. Methodology: The authors identified 102,514 patients of diagnosed chronic lymphocytic leukemia In SEER Research Plus Data, 17 Registries, from 2000-2021 using ICD code C91.1. Data was stratified based on age, gender, race, chemotherapy status. Results were compared using Log-Rank test (GraphPad Prism). Results: Of the 102,514 cases reported, 60.2% were male and 39.8% were female. The majority of patients were White (83.3%), followed by Black (6.6%), Hispanic (5.6%), Asian (2.3%), and 1.3% were of unknown ethnicity. All differences were statistically significant. Median survival (MS) in younger patients (ages 18–65) was 219 months, compared to 80 months in patients over 65 years (p < 0.0001). Median survival in patients who received chemotherapy was 82 months, whereas it was 116 months in those who did not receive chemotherapy. The median survival for all patients diagnosed between 2000–2015 was 108 months. For patients diagnosed between 2016–2021, the median survival was undefined, likely reflecting longer ongoing survival due to newer treatments. Conclusion: Given the indolent nature of CLL, patients who received chemotherapy showed lower median survival—possibly reflecting treatment-related toxicity. Younger patients demonstrated better outcomes, while the geriatric population had poorer survival, likely due to comorbidities. The significantly higher incidence in the White population suggests potential genetic or environmental factors that warrant further investigation. The notable undefined median survival in the recent cohort suggests prolonged survival benefits, seen after the introduction of targeted therapies, particularly BTK inhibitors. Further long-term studies are needed to better understand the full impact of these therapies and refine treatment strategies.