ReviewTherapeutic advances in hematology2026
Novel targeted therapies for central nervous system involvement in chronic lymphocytic leukemia: A systematic review.
Review in Therapeutic advances in hematology, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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4 authors.
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Abstract
Background: Central nervous system (CNS) involvement in chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL) is rare, diagnostically challenging, and historically associated with poor outcomes. Bruton tyrosine kinase (BTK) and B-cell lymphoma 2 (BCL2) inhibitors may improve outcomes, but evidence remains limited to case reports and small series. Objectives: To summarize the clinical features, diagnostic findings, treatment patterns, efficacy, safety, and outcomes of CNS involvement by CLL/SLL treated with novel targeted therapies. Design: Systematic review of published case reports, case series, and cohorts with extractable individual-level data. Methods: PubMed, Scopus, and Web of Science were searched from database inception to September 15, 2025. Eligible studies reported adults with CNS involvement by CLL/SLL treated with targeted agents, including BTK inhibitors, venetoclax, duvelisib, dasatinib, or other novel therapies. Chemotherapy-only regimens and Richter transformation cases were excluded. Patient-level data were extracted, and study quality was assessed using the Murad tool. Results: Twenty-six studies including 32 patients were analyzed. Median age at CNS presentation was 65.5 years, and most cases occurred at relapse. CNS disease was meningeal in 47%, parenchymal in 22%, and combined in 31%. Adverse biological features, including TP53 mutation, del(17p), and unmutated immunoglobulin heavy chain variable region (IGHV), were common. Across 34 treatment regimens, the overall response rate was 94.1%, with 55.9% complete and 38.2% partial responses. Ibrutinib was the most frequently used agent, while venetoclax and ibrutinib-venetoclax showed favorable activity. Other targeted agents showed promising responses in isolated cases. Toxicities were infrequent and consistent with known safety profiles. Conclusion: BTK inhibitor- and venetoclax-based regimens show encouraging activity in CNS involvement by CLL/SLL, including in genomically adverse disease. However, the current evidence remains primarily exploratory and descriptive. Prospective multicenter studies are warranted to establish optimal treatment sequencing, combination strategies, and the role of adjunctive intrathecal therapy or radiotherapy.
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