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Neurological adverse effects due to programmed death 1 (PD-1) inhibitors

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Abstract

Purpose

PD-1 Immunotherapy is integral in treating multiple cancers, but has been associated with neurological adverse events (nAEs). Our study was aimed at identifying the clinical spectrum of nAEs associated with pembrolizumab and nivolumab.

Methods

We performed an IRB approved single-center retrospective cohort study on patients receiving either pembrolizumab or nivolumab. Patients that developed nAEs within 12 months of treatment were identified. Descriptive statistics were conducted, and differences between groups were analyzed by the Chi-square or t test method.

Results

In total, 649 patients were identified. Seventeen patients (2.6%) developed nAEs. Eight of those were on pembrolizumab and nine were on nivolumab. Average age was 62.1 years. Ten were males and 7 were females. Most patients had melanoma (6, 35.3%). Patients who developed nAEs more frequently had intracranial lesions at initiation of anti PD-1 therapy compared to those who did not develop nAEs (76.5% vs 27.8%; p-value < 0.001). Fifteen patients (88.2%) permanently stopped PD-1 therapy. In 8 patients, treatment termination resolved symptoms attributed to immune checkpoint blockade. The majority of patients developed grade 3 or 4 nAEs (10 patients, 58.8%), and required hospitalization (11 patients, 64.7%). Eight patients died for nAEs referable causes.

Conclusion

Pembrolizumab and nivolumab are associated with the development of nAEs associated with increased risk of permanent discontinuation of treatment, hospitalization, and death. Melanoma patients might be at a particularly high risk of such side effects. Future studies are still required to better assess which patients benefit most from such therapies, while minimizing the risk of complications.

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Acknowledgements

We would like to thank all patients who participated in our study.

Funding

No financial support or fund was granted for the making of this project.

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Authors and Affiliations

Authors

Contributions

Experimental Design and Implementation: SS, JAJ, MJ, RK, VV, EE, RT and JM. Data Analysis and Interpretation: SS, JAJ, MJ, RK, VV, EE, RT and JM. Writing of the Manuscript: SS, JAJ, MJ, RK, VV, EE, RT and JM. Approval of Final Version: all co-authors.

Corresponding author

Correspondence to Justin M. Moore.

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The authors declare no conflict of interest in the making of this project.

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Shi, S., Jaoube, J.A., Kanwar, R. et al. Neurological adverse effects due to programmed death 1 (PD-1) inhibitors. J Neurooncol 148, 291–297 (2020). https://doi.org/10.1007/s11060-020-03514-8

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  • DOI: https://doi.org/10.1007/s11060-020-03514-8

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