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Intracranial Tumor Control After Immune-Related Adverse Events and Discontinuation of Immunotherapy for Melanoma.

Authors :
Zhang M
Rodrigues AJ
Bhambhvani HP
Fatemi P
Pollom EL
Gibbs IC
Thomas RP
Soltys SG
Hancock SL
Chang SD
Reddy SA
Gephart MH
Li G
Source :
World neurosurgery [World Neurosurg] 2020 Dec; Vol. 144, pp. e316-e325. Date of Electronic Publication: 2020 Aug 24.
Publication Year :
2020

Abstract

Objective: Immunotherapy for patients with melanoma with brain metastasis has significantly improved outcomes; however, it has also been characterized by potentially dangerous immune-related adverse events (IRAEs). Several reports have suggested that these reactions can precede improved treatment responses. For intracranial disease control, we sought to identify if such an association exists.<br />Methods: We conducted a retrospective chart review of patients with melanoma who underwent immunotherapy treatment after diagnosis of brain metastasis. The study cohort was then stratified into 2 groups based on their history of developing an IRAE that prompted discontinuation of that regimen. The primary outcome variable included intracranial progression-free survival (PFS). Kaplan-Meier and Cox proportional hazard analyses were used to evaluate survival and predictors of outcomes.<br />Results: Fifty-two patients met the inclusion criteria, 17 of whom experienced severe IRAEs that led to discontinuation of immunotherapy. Median intracranial PFS was 19.9 versus 10.5 months (P = 0.053) in patients who did and did not experience severe IRAEs prompting discontinuation, respectively. No additional outcome benefits were identified for systemic PFS or overall survival (mean, 33.1 months and 27.6 months, respectively). Multivariable analysis identified BRAF mutation status as a negative prognosticator of brain progression (P = 0.013; hazard ratio, 3.90). Initial treatment with BRAF inhibitor was also a negative predictor of all-cause mortality (P = 0.015; hazard ratio, 10.73).<br />Conclusions: Immune-related adverse events may signify an underlying immunogenic response that has intracranial disease control benefits. Despite their associated side effects, immunotherapies continue to show promising outcomes as a first-line agent for melanoma with brain metastasis.<br /> (Copyright © 2020 Elsevier Inc. All rights reserved.)

Details

Language :
English
ISSN :
1878-8769
Volume :
144
Database :
MEDLINE
Journal :
World neurosurgery
Publication Type :
Academic Journal
Accession number :
32853767
Full Text :
https://doi.org/10.1016/j.wneu.2020.08.124