SynthesisFrontiers in oncology2026
Safety and efficacy of CAR T-cell therapy in central nervous system lymphoma: a systematic review and meta-analysis.
Synthesis in Frontiers in oncology, 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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Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Authors and funding
10 authors.
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Abstract
Background: The safety and efficacy of Chimeric Antigen Receptor (CAR) T-cell therapy in Central Nervous System Lymphoma (CNSL) remain uncertain, given the limited representation of CNS involvement in pivotal CAR T-cell trials. This meta-analysis synthesized data from studies evaluating outcomes in both primary (PCNSL) and secondary CNS lymphoma (SCNSL) cohorts treated with CART. Methods: A comprehensive search was performed across PubMed, Embase, and clinical registries up to October 2025. Studies reporting efficacy or toxicity outcomes in CNSL following CD19-targeted CART therapy were included. Proportions were stabilized using the Freeman-Tukey double arcsine transformation and pooled using inverse variance weighting. Between-study heterogeneity was estimated with the DerSimonian-Laird method, and τ² confidence intervals were calculated via the Jackson approach. Publication bias was assessed using Egger's regression. Subgroup and multiple meta-regression analyses evaluated moderators including CNS category (PCNSL vs SCNSL) and publication year. Results: Data from thirty-eight studies were meta-analyzed. The pooled overall response rate (ORR) was 0.75 [95% CI: 0.70-0.79] with moderate-to-substantial heterogeneity (I² = 53.3%). Complete response (CR) rate was 0.52 [0.46-0.58], and partial response (PR) rate 0.18 [0.14-0.22]. No significant publication bias was detected (Egger's p = 0.39 for ORR). Meta-regression indicated no significant effect of publication year or lymphoma subtype on response. Cytokine Release Syndrome (CRS) occurred in 83.5% [79.0-88.0], with grade ≥3 CRS in 5.77% [3.0-9.0]. Immune Effector Cell-Associated Neurotoxicity Syndrome (ICANS) was reported in 44.9% [36.0-54.0], with severe (grade ≥3) events in 17.4% [12.0-23.0]. Heterogeneity was substantial for ICANS (I² = 84.2%) but moderate for CRS (I² = 64.3%). Conclusions: CART therapy achieves robust response rates in CNS lymphoma, with efficacy comparable between PCNSL and SCNSL. Neurotoxicity remains frequent but manageable, and severe CRS events are infrequent. Systematic review registration: https://www.crd.york.ac.uk/prospero/, identifier CRD420251070033.
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