Check point inhibitors and Autoimmunity: A Call for an Evidence Based Update

Immune checkpoint inhibitors are a novel form of transformative antitumor targeted therapies that have dramatically changed the therapeutic landscape for malignancies. These forms of targeted therapies mostly tackle patients with metastatic solid tumors offering a long- term benefit. Does the outweigh the risk? A question there that needs an evidence- based answer. In fact, their benefit was never free of an advert risk related to the targeted activation of immune cells against self-antigens provoking an “immune-related adverse events” (irAEs) with myriad systemic manifestations. The currently onboard checkpoint inhibitors in cancer targeted therapy have included a number of agents including agents targeting cytotoxic T-lymphocyte–associated antigen 4 (CTLA-4), programmed death 1 (PD-1), and its ligand (PD-L1). These agents were found to unleash key negative regulators of immune activation “removing the brakes” sparking an effective antitumor immune response. However, a list of immune related adverse events have been related to their use, including colitis, hepatitis, hypophysitis, thyroiditis, and dermatitis (anti–CTLA4 antibodies), pneumonitis, inflammatory arthritis (Anti–PD-1 agents), they may occasionally also cause systemic syndromes that are seemingly identical to known rheumatologic disorders (eg, Sjögren syndrome, sarcoidosis). Although these side effects can typically be managed with corticosteroids and other immunosuppressants, highly morbid and even fatal events can occur in a small proportion of patients. Predicting which patients will experiences irAEs and mitigating the risk of severe organ injury remain a critical unmet need.

Author(s): Reem Hamdy Abdellatif Mohammed  

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