Impact of chemotherapy and immunotherapy on survival in pediatric primary diffuse leptomeningeal melanomatosis: a systematic review and pooled survival analysis.

PURPOSE: Pediatric primary diffuse leptomeningeal melanomatosis (PDLM) is a rare, aggressive malignancy with no established standard of care. We performed an integrated survival analysis to characterize disease course and identify treatment factors associated with overall survival (OS).

METHODS

A systematic literature search of PubMed, Embase, and Scopus (2000-2025) was conducted in accordance with PRISMA guidelines. Eligible studies included patients < 18 years with histopathologically confirmed PDLM per 2021 World Health Organization and Expert Care for Rare Adult Solid Cancers criteria and reported OS and treatment data. Survival was assessed using Kaplan-Meier analyses, with univariable and multivariable Cox proportional hazards regression.

RESULTS

Thirty-three pediatric PDLM cases were identified (57.6% male; median age 10 [IQR 3-14] years). Diagnosis was established via tissue sampling in 72.7%, cerebrospinal fluid cytology in 21.2%, and both in 6.1%. Among 13 patients with molecular testing, 69.2% harbored NRAS mutations. Twenty-four patients (72.7%) received treatment: chemotherapy (70.7%), radiation therapy (41.7%), and immunotherapy (62.5%). Median OS was 5.0 [3.5-7.0] months. On Kaplan-Meier analysis, immunotherapy was associated with improved OS (p < 0.001), including when combined with radiation (p = 0.038), chemotherapy (p = 0.006), or both (p = 0.048). Univariable Cox regression showed immunotherapy to be significantly associated with reduced hazard of death (HR 0.23 [0.10-0.51], p < 0.001). On multivariable analysis, immunotherapy (HR 0.22 [0.10-0.49], p < 0.001) and chemotherapy (HR 0.44 [0.21-0.94], p = 0.035) were independently associated with improved OS.

CONCLUSION

Pediatric PDLM carries a uniformly poor prognosis. Immunotherapy and chemotherapy were the only treatments independently associated with improved survival, highlighting their central role in management of this rare disease.