Posterior Reversible Encephalopathy Syndrome (PRES) and Drug-Induced Hypersensitivity Syndrome (DIHS) followingImmunotherapy and BRAF/MEK Inhibition with ContinuedResponse in Metastatic Melanoma

The role of immunotherapy continues to evolve across both solid and hematologic malignancies. However, while useof immunotherapy has increased via the advent of checkpoint inhibition, chimeric antigen receptors, and vaccines againstmalignant cells, there remains uncertainty regarding the recognition and management of delayed immune-related reactions andpost treatment immune-related sensitivity to subsequent medications, such as BRAF/MEK kinase inhibitors. Furthermore, it isunclear how immunotherapy may alter the adverse effect profile and efficacy of subsequent lines of treatment.Case Presentation.Discussed is a patient with stage IV metastatic melanoma who failedfirst-line treatment with a combination of nivolumab andipilimumab. He was then treated with BRAF/MEK kinase inhibition via Encorafenib and Binimetinib. Shortly thereafter, thepatient developed posterior reversible encephalopathy syndrome (PRES) and a generalized pruritic rash that was biopsied withconsideration toward drug reaction versus drug-induced hypersensitivity syndrome (DIHS), formerly called drug reaction witheosinophilia and systemic symptoms (DRESS). The BRAF/MEK combination was held and steroid taper initiated withcontinued response even beyond conclusion of the steroid taper.Discussion and Conclusions.This case highlights the diagnosticchallenge presented by PRES and DIHS in the setting of immunotherapy and BRAF/MEK kinase inhibition for malignantmelanoma. The clinical rationale for reinitiating therapy following severe immune reactions subsequent to immunotherapy inthe setting of relapsed/refractory metastatic melanoma is discussed. Additionally, the durable response our patient experiencedthroughout the drug hold period and steroid taper and its clinical potential etiologies and applications are reviewed. Ascheckpoint inhibition and tyrosine-kinase inhibitors have become cornerstones of cancer therapy, larger studies and long-termobservations are needed to investigate the risks and benefits across different sequences of therapy