TREATMENT SEQUENCING AND LINE-OF-THERAPY PATTERNS IN THE BTKI ERA: REAL-WORLD EVIDENCE FROM 24,410 CHRONIC LYMPHOCYTIC LEUKEMIA (CLL) PATIENTS USING NORSTELLALINQ
Author(s)
Isabella Even-Chen, BA1, ilan behm, MPH2, Shefali Patel, PhD3, Rahul Das, PhD4, Atharva Manjrekar, MS5, Juan Diego Irizarry-Cole, PhD1, Allison Perry, PhD1.
1Norstella, New York, NY, USA, 2Norstella, Englewood, CO, USA, 3Norstella, Ferndale, MI, USA, 4Norstella, Yardley, PA, USA, 5Norstella, West Hartford, CT, USA.
1Norstella, New York, NY, USA, 2Norstella, Englewood, CO, USA, 3Norstella, Ferndale, MI, USA, 4Norstella, Yardley, PA, USA, 5Norstella, West Hartford, CT, USA.
OBJECTIVES: To characterize treatment sequencing transitions, regimen utilization across lines of therapy, BTKi rechallenging and switching patterns, and line-level treatment duration among patients with Chronic Lymphocytic Leukemia (CLL) using a large real-world linked dataset.
METHODS: A retrospective cohort study was conducted using NorstellaLinQ’s US real-world dataset of linked open claims, structured EHR, and clinical notes (January 2019-September 2025). Among 204,756 incident CLL patients, 24,410 initiated systemic treatment. Lines of therapy were assigned using gap-based rules (>90-day gap defined a new line). Regimens were categorized as BTKi monotherapy, BCL-2-based, BTKi plus targeted, chemoimmunotherapy, PI3K inhibitors, and other. Sequencing transitions, switching rates, BTKi rechallenge, and average line duration were assessed overall and by biomarker status.
RESULTS: BTKi monotherapy was the dominant first-line regimen (average duration 331 days), with the treatment population narrowing substantially across lines (24,410 at line 1; 5,356 at line 2; 1,496 at line 3; 479 at line 4). The most common second-line transition following frontline BTKi therapy was BTKi-to-BCL-2 switching, followed by within-class BTKi cycling. Regimen heterogeneity increased in later lines, encompassing non-covalent BTKi, PI3K inhibitors, and cellular therapies. BTKi rechallenging was observed across lines. Among patients with human-in-the-loop large language model (LLM) extracted TP53 mutation or del(17p), earlier treatment initiation (43% within 90 days) and higher rates of later-line escalation were observed.
CONCLUSIONS: BTKi-based therapy remains the predominant treatment approach across lines of therapy in real-world CLL practice. While first-line management is relatively homogeneous, later-line treatment demonstrates increasing regimen diversity and reflects increasing therapeutic complexity, particularly among patients with high-risk molecular features. These findings provide contemporary real-world benchmarks for evaluating emerging therapies in CLL.
METHODS: A retrospective cohort study was conducted using NorstellaLinQ’s US real-world dataset of linked open claims, structured EHR, and clinical notes (January 2019-September 2025). Among 204,756 incident CLL patients, 24,410 initiated systemic treatment. Lines of therapy were assigned using gap-based rules (>90-day gap defined a new line). Regimens were categorized as BTKi monotherapy, BCL-2-based, BTKi plus targeted, chemoimmunotherapy, PI3K inhibitors, and other. Sequencing transitions, switching rates, BTKi rechallenge, and average line duration were assessed overall and by biomarker status.
RESULTS: BTKi monotherapy was the dominant first-line regimen (average duration 331 days), with the treatment population narrowing substantially across lines (24,410 at line 1; 5,356 at line 2; 1,496 at line 3; 479 at line 4). The most common second-line transition following frontline BTKi therapy was BTKi-to-BCL-2 switching, followed by within-class BTKi cycling. Regimen heterogeneity increased in later lines, encompassing non-covalent BTKi, PI3K inhibitors, and cellular therapies. BTKi rechallenging was observed across lines. Among patients with human-in-the-loop large language model (LLM) extracted TP53 mutation or del(17p), earlier treatment initiation (43% within 90 days) and higher rates of later-line escalation were observed.
CONCLUSIONS: BTKi-based therapy remains the predominant treatment approach across lines of therapy in real-world CLL practice. While first-line management is relatively homogeneous, later-line treatment demonstrates increasing regimen diversity and reflects increasing therapeutic complexity, particularly among patients with high-risk molecular features. These findings provide contemporary real-world benchmarks for evaluating emerging therapies in CLL.
Conference/Value in Health Info
2026-11, ISPOR Europe 2026, Vienna, Austria
Value in Health, Volume 29, Issue 12S
Code
RWD128
Topic
Clinical Outcomes, Epidemiology & Public Health, Real World Data & Information Systems
Topic Subcategory
Health & Insurance Records Systems
Disease
Oncology