ArticleFrontiers in immunology2026
Clinical outcomes of intrathecal anti-PD-1 therapy with or without whole-brain radiotherapy in melanoma leptomeningeal metastasis: a multicenter retrospective study.
Article in Frontiers in immunology, 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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Abstract
Background: Leptomeningeal metastases (LM) from melanoma are rare and associated with dismal outcomes. Intrathecal PD-1 antibody therapy has shown encouraging activity in LM. Radiotherapy may enhance tumor immunogenicity and potentially augment immune checkpoint blockade within the central nervous system. The efficacy and safety of combining intrathecal PD-1 antibodies with whole-brain radiotherapy (WBRT) in melanoma LM remain unclear. Methods: We retrospectively reviewed melanoma patients with LM who received intrathecal PD-1 antibody therapy between June 2022 and December 2024. Patients were categorized according to whether WBRT was administered within 30 days of intrathecal PD-1 antibody therapy: intrathecal monotherapy and combination therapy. Overall survival (OS) and intracranial progression-free survival (iPFS) were descriptively evaluated by treatment exposure, with between-group analyses considered exploratory and hypothesis-generating. Adverse events were graded using CTCAE v5.0. Results: 20 patients were included, of whom 7 received intrathecal PD-1 antibody monotherapy and 13 received intrathecal PD-1 antibody therapy combined with WBRT. The observed median OS was 20.1 weeks (95% CI, 13.3-not reached) in the intrathecal monotherapy group and 45.3 weeks (95% CI, 28.7-not reached) in the combination group. The observed median iPFS was 10.0 weeks (95% CI, 6.1-not reached) and 23.0 weeks (95% CI, 18.4-not reached), respectively. Treatment-related adverse events were manageable, and no new safety signals were identified. Conclusion: Intrathecal PD-1 antibody therapy combined with WBRT showed numerically longer OS and iPFS than intrathecal therapy alone in this small retrospective descriptive series of melanoma leptomeningeal metastasis. These hypothesis-generating findings warrant prospective investigation but do not establish comparative efficacy.
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