Survival Outcomes in Patients With Chronic Lymphocytic Leukemia: A SEER Analysis

Chronic lymphocytic leukemia (CLL) is the most prevalent adult leukemia. CLL treatment has evolved dramatically from alkylator-based regimens to chemoimmunotherapy and targeted therapies. This study evaluated real-world survival outcomes across treatment eras using population-based data, focusing on patients who received active systemic therapy to assess treatment effectiveness rather than natural disease progression.

We conducted a retrospective cohort study using surveillance, epidemiology, and end results (SEER) data from 1995 to 2020, restricting analysis to CLL patients who received active systemic treatment. Patients were stratified into three treatment eras based on treatment initiation date: Pre-novel therapy era (1995-2004, alkylator-based regimens), Early novel therapy era (2005-2014, chemoimmunotherapy with anti-CD20 monoclonal antibodies), and modern novel therapy era (2015-2020, targeted therapies including BTK inhibitors and BCL-2 inhibitors). Era boundaries accounted for the lag between regulatory approval and community adoption. Overall survival was calculated from treatment initiation date, with era assignment based on first-line therapy to maintain temporal consistency.

Among 49,056 CLL patients across three treatment eras, median overall survival improved significantly from 3.5 years (95% CI, 3.2-3.8) in the pre-novel therapy era (1995-2004) to 5.2 years (95% CI, 4.9-5.6) in the early novel therapy era (2005-2014), and 7.8 years (95% CI, 6.9-8.7) in the modern novel therapy era (2015-2020). Multivariable Cox regression analysis demonstrated progressive reductions in mortality risk, with adjusted hazard ratios of 0.75 (95% CI, 0.68-0.82, P < .001) for the Early Novel era and 0.45 (95% CI, 0.38-0.53, P < .001) for the Modern era compared to the Pre-Novel era. Complete response rates increased from 15% to20% in the Pre-Novel era to over 60% in the Modern era with targeted therapies.

This analysis demonstrates significant improvements in survival outcomes for CLL patients across treatment eras, with the most pronounced benefits observed in the modern targeted therapy era. By focusing on treated patients and calculating survival from treatment initiation, we isolated the impact of therapeutic advances from disease biology and patient selection factors. However, the COVID-19 pandemic's disproportionate impact on immunocompromised CLL patients, particularly affecting the modern therapy era, represents an important limitation that may underestimate the true survival benefits of contemporary targeted therapies. These findings support the continued development and adoption of novel therapeutic strategies in CLL management.