Impact of Novel Therapies on Survival in Chronic Lymphocytic Leukemia: Insights from SEER Database
Authors: Peshin Supriya , Modi Shivani , Moka Nagaishwarya 
Published: December 2024

Abstract: This study investigates survival outcomes in patients with Chronic Lymphocytic Leukemia (CLL) across different treatment eras, focusing on assessing the impact of novel therapies introduced in recent years. Using data from the SEER (Surveillance, Epidemiology, and End Results) database, we aim to provide a comprehensive analysis of how advancements in treatment have influenced survival rates.

Introduction: CLL is a common type of leukemia in adults, characterized by the accumulation of functionally incompetent lymphocytes. Over the past few decades, the treatment landscape for CLL has evolved significantly, particularly with the introduction of novel therapies such as targeted agents, monoclonal antibodies, and CAR-T cell therapy This study aims to evaluate survival outcomes across different treatment eras to understand the impact of these advancements.

Methods: Data were obtained from the SEER database, which includes detailed information on cancer incidence, survival, and treatment across multiple regions in the United States. Patients diagnosed with CLL from 1995 to 2020 were included. The population was divided into three treatment eras:

Pre-novel Therapy Era (1995-2004): Primarily chemotherapy-based treatments,

Early Novel Therapy Era (2005-2014): The introduction of targeted agents such as ibrutinib and monoclonal antibodies like rituximab,

Modern Novel Therapy Era (2015-2020): Advanced targeted therapies, including newer generation BTK inhibitors and BCL-2 inhibitors, as well as CAR-T cell therapy.

Demographic data (age, sex, race) and clinical characteristics (stage at diagnosis) were extracted. The median age at diagnosis was 72 years, with a male-to-female ratio of approximately 1.5:1. Kaplan-Meier survival curves were used to estimate overall survival (OS) for each era. Cox proportional hazards models were employed to assess the impact of treatment era on survival, adjusting for potential confounders.

Results: A total of 50,000 patients diagnosed with CLL were identified from the SEER database spanning the years 1995 to 2020. The cohort was divided into three distinct treatment eras: 1995-2004 (Pre-Novel Therapy Era), 2005-2014 (Early Novel Therapy Era), and 2015-2020 (Modern Novel Therapy Era). Demographic characteristics, including age, sex, and race, were consistent across the eras, reflecting the general population distribution of CLL patients.

Survival Outcomes: Overall survival (OS) improved notably across the treatment eras. The Kaplan-Meier estimated OS rates at 5 years were approximately 65% in the Pre-Novel Therapy Era, 75% in the Early Novel Therapy Era, and 85% in the Modern Novel Therapy Era. Similarly, 10-year OS rates demonstrated a progressive increase from approximately 45% in the Pre-Novel Therapy Era to 60% in the Modern Novel Therapy Era.

Impact of Treatment Era: In adjusted Cox proportional hazards models, the treatment era was significantly associated with improved survival outcomes. Compared to the Pre-Novel Therapy Era, patients in the Early Novel Therapy Era exhibited a 20% reduction in the risk of mortality (HR 0.80, 95% CI: 0.75-0.85). This trend was further enhanced in the Modern Novel Therapy Era, where the risk of mortality decreased by 40% compared to the Pre-Novel Therapy Era (HR 0.60, 95% CI: 0.55-0.65).

Discussion: The findings highlight significant advancements in CLL management over recent decades, primarily due to novel therapies. Targeted agents such as monoclonal antibodies and CAR-T cell therapy, have notably improved survival, especially in the Modern Novel Therapy Era. Transitioning from traditional chemotherapy to novel therapies has enhanced outcomes in CLL with a better adverse effect profile. However, the study's limitations include one or two retrospective study biases, regional variations in treatment protocols, and incomplete documentation of specific treatments.

Conclusion: In conclusion, this study demonstrates improvements in overall survival with the advent of novel therapies in CLL, although it improved treatment outcomes significantly, adverse effect profiles of these medications continue to be a challenge in this population which leaves room for optimization and further innovation in the field