A Double-Edged Sword - Multiorgan Dysfunction as a Rare Complication of Dual Checkpoint Immunotherapy

Abstract

against the tumor. This disruption in the functioning of immune checkpoint molecules can lead to imbalances in immunologic tolerance that results in an unchecked immune response. This may clinically manifest with autoimmune-like/inflammatory side-effects, which cause collateral damage to normal organ systems and tissues. Such adverse events, termed ‘immunerelated adverse events’ (irAEs), are also thought to be principally T-cell mediated, however other immune cells may play a role in the development of irAEs, including B cells that secrete antibodies which mediate toxicity, as well as granulocytes that secrete inflammatory mediators and cytokines [1]. Of note, the incidence of cardiac toxicity owing to ICIs is rare (occur-ring in < 1% of patients) but can be fulminant and potentially fatal. Neurologic complications are also rare and when all neurological irAEs are pooled, an incidence of 3.8% for CTLA-4 inhibitors, 6% for PD-1 inhibitors and 12% for combination therapy has been reported in one review of 59 clinical trials, and encephalitis has been reported in 0.3% of patients taking ICIs. Lastly, an overall incidence of 2.2% was reported for acute kidney injury (0.6% for grades 3 and 4 renal events) in one systematic review of randomized controlled trials including 3,695 patients treated with ICIs [4]. Here we present a unique case that highlights the impact Opdivo and Yervoy induced irAEs had on our patient and explore this unique case of these monoclonal antibodies causing simultaneous damage to the central nervous system via immune checkpoint inhibitor induced encephalitis, cardiovascular system via acute decompensated left ventricular heart failure Introduction