Medical Student (M3) Case Western Reserve University School of Medicine Little Rock, AR, US
Disclosure(s):
Nikita Das, B.A. Neuroscience and Behavior: No financial relationships to disclose
Introduction: Melanoma accounts for 5% of new cancer cases in the U.S. each year and has a 5-year survival rate of 93.5%, reflecting a decrease in mortality rates accompanying the arrival of several immunotherapies on the market. Though incidence of neurologic side effects of PD-1 inhibitors is estimated between 5-12%, the impact of these complications on treatment course and metastatic prognosis calls for further investigation. The purpose of this study is to examine whether PD-1 immunotherapy increases risk for adverse neurologic events in melanoma patients.
Methods: A retrospective study on TriNetX – research network of 60 U.S. healthcare organizations – identified adult melanoma patients. Cohort 1(n=1,460,509) included melanoma patients with no history of PD-1 inhibitor therapy. Cohort 2(n=22,936) included melanoma patients treated with pembrolizumab or nivolumab following diagnosis. Propensity Score Matching generated final cohorts(n=22,936) using covariates: gender, race, age, and history of nervous system disease or neurodevelopmental disorders. Relative Risk was determined within 5 years for the occurrence of neurologic complications - selected based on consensus disease definitions for neurologic immune-related adverse events of immune checkpoint inhibitors.
Results: Compared to melanoma patients with no history of pembrolizumab or nivolumab in their treatment course, patients who received PD-1 inhibitors exhibited significantly increased risk of meningitis(p < 0.0001), encephalitis(p < 0.0001), demyelinating syndromes(p < 0.0001), PNS neuropathy(p < 0.0001), neuromuscular junction disorders(p < 0.0001), and inflammatory myopathy(p=0.0005). Risk of CNS vasculitis did not differ between cohorts(p=.99).
Conclusion : This study evidences that melanoma patients receiving PD-1 inhibitor therapies are at greater risk of experiencing immune-related neurologic adverse events than patients on other treatment regimens. These findings underscore the need for more specific drug delivery mechanisms of immunotherapy to cancerous cells in order to minimize adverse side effects.
