REAL-WORLD EVIDENCE (RWE) ON BRUTON TYROSINE KINASE INHIBITORS (BTKIS) IN TREATMENT-NAIVE (TN) CHRONIC LYMPHOCYTIC LEUKEMIA (CLL) OR SMALL LYMPHOCYTIC LYMPHOMA (SLL): AN ARTIFICIAL INTELLIGENCE (AI)-ASSISTED LITERATURE REVIEW
Author(s)
Allie Cichewicz, PhD1, Xiaoliang Wang, PhD, MPH2, Keri Yang, PhD2, Gregory A. Maglinte, PhD, MPH2, Kevin Kallmes, BS, MA, JD1, Erlene Seymour, MD2;
1Nested Knowledge Inc, Saint Paul, MN, USA, 2BeOne Medicines, Ltd, San Carlos, CA, USA
1Nested Knowledge Inc, Saint Paul, MN, USA, 2BeOne Medicines, Ltd, San Carlos, CA, USA
OBJECTIVES: Covalent BTKis (zanubrutinib, acalabrutinib, ibrutinib) have greatly improved the outcomes of patients with CLL/SLL and have become standard of care. However, without clinical trials comparing BTKi in patients with TN CLL, RWE is critical to assess comparative effectiveness and use across broader patient populations. This review synthesizes RWE evaluating clinical outcomes and healthcare resource utilization (HCRU) with BTKi monotherapies in TN CLL/SLL.
METHODS: Search strings generated with Smart Search, an AI tool, were reviewed by experts and run across Medline/Embase, covering 2018-2025. AI Screening was performed using human-configured criteria; all AI decisions were expert-curated. Eligible comparative RWE studies assessed BTKis and reported effectiveness, safety, or HCRU outcomes in TN CLL/SLL. Data were extracted using AI recommendations with human validation.
RESULTS: Of 1256 identified citations, 24 records (13 unique studies) were included. Most were published in 2024-2025 (21/24 [88%]) and were conference presentations (22/24 [92%]). Nearly all studies (12/13 [93%]) were retrospective cohort studies conducted in the United States. Nine studies (69%) reported effectiveness outcomes, none reported progression-free survival or response, and four (31%) reported HCRU. Adjusted for baseline characteristics, zanubrutinib demonstrated better effectiveness versus ibrutinib across outcomes: overall survival (OS) adjusted hazard ratio (95% CI) 0.46 (0.28-0.76); time to next treatment (TTNT) 0.59 (0.44-0.79); time to discontinuation (TTD) 0.56 (0.44-0.72). Compared to acalabrutinib, zanubrutinib had better TTD (0.51; 0.33-0.74) but no significant difference in OS or TTNT. For HCRU, zanubrutinib demonstrated the lowest inpatient burden (2.5 admissions PPPY).
CONCLUSIONS: RWE comparing BTKis in TN CLL/SLL remains limited; however, recent presentations indicate that ongoing research is actively progressing. This review found better real-world effectiveness and reduced HCRU burden for zanubrutinib versus other BTKis. This study also demonstrated that use of AI in literature review helped increase efficiency, which will allow future updates to capture emerging real-world evidence in CLL/SLL.
METHODS: Search strings generated with Smart Search, an AI tool, were reviewed by experts and run across Medline/Embase, covering 2018-2025. AI Screening was performed using human-configured criteria; all AI decisions were expert-curated. Eligible comparative RWE studies assessed BTKis and reported effectiveness, safety, or HCRU outcomes in TN CLL/SLL. Data were extracted using AI recommendations with human validation.
RESULTS: Of 1256 identified citations, 24 records (13 unique studies) were included. Most were published in 2024-2025 (21/24 [88%]) and were conference presentations (22/24 [92%]). Nearly all studies (12/13 [93%]) were retrospective cohort studies conducted in the United States. Nine studies (69%) reported effectiveness outcomes, none reported progression-free survival or response, and four (31%) reported HCRU. Adjusted for baseline characteristics, zanubrutinib demonstrated better effectiveness versus ibrutinib across outcomes: overall survival (OS) adjusted hazard ratio (95% CI) 0.46 (0.28-0.76); time to next treatment (TTNT) 0.59 (0.44-0.79); time to discontinuation (TTD) 0.56 (0.44-0.72). Compared to acalabrutinib, zanubrutinib had better TTD (0.51; 0.33-0.74) but no significant difference in OS or TTNT. For HCRU, zanubrutinib demonstrated the lowest inpatient burden (2.5 admissions PPPY).
CONCLUSIONS: RWE comparing BTKis in TN CLL/SLL remains limited; however, recent presentations indicate that ongoing research is actively progressing. This review found better real-world effectiveness and reduced HCRU burden for zanubrutinib versus other BTKis. This study also demonstrated that use of AI in literature review helped increase efficiency, which will allow future updates to capture emerging real-world evidence in CLL/SLL.
Conference/Value in Health Info
2026-05, ISPOR 2026, Philadelphia, PA, USA
Value in Health, Volume 29, Issue S6
Code
SA14
Topic
Study Approaches
Topic Subcategory
Literature Review & Synthesis
Disease
SDC: Oncology