Severe cytokine release syndrome in a patient receiving PD‐1‐directed therapy

Abstract

Cytokine release syndrome (CRS) is a phenomenon of immune hyperactivation described in the setting of cellular and bispecific T-cell engaging immunotherapy. Checkpoint blockade using anti-programmed cell death 1 (anti-PD-1) inhibitors is an approach to antitumor immune system stimulation. A 29-year-old female with alveolar soft part sarcoma developed severe CRS after treatment with anti-PD-1 therapy. CRS was characterized by high fevers, encephalopathy, hypotension, hypoxia, hepatic dysfunction, and evidence of coagulopathy, and resolved after infusion of the interleukin-6 inhibitor tocilizumab and corticosteroids.

Colitis after checkpoint blockade: A retrospective cohort study of melanoma patients requiring admission for symptom control

“…In general, the self‐targeting seen in irAEs is felt to be the result of an underlying predisposition to autoimmunity, with or without shared tumor‐tissue antigenicity, triggered by disinhibited T‐lymphocytes . There seem to be multiple mechanisms through which such cells act to produce symptoms of autoimmune disease: for example, direct tissue infiltration is seen in vitiligo and myocarditis; autoantibody generation is seen in myasthenia gravis and meningoencephalitis; and toxicities mediated by inflammatory cytokines are seen in PD‐1 inhibitor‐induced cytokine release syndrome …”

“…12,21 There seem to be multiple mechanisms through which such cells act to produce symptoms of autoimmune disease: for example, direct tissue infiltration is seen in vitiligo and myocarditis 21,22 ; autoantibody generation is seen in myasthenia gravis and meningoencephalitis 23,24 ; and toxicities mediated by inflammatory cytokines are seen in PD-1 inhibitor-induced cytokine release syndrome. 25 From previously published data, CPI-related GEC was typically present with diarrhea, abdominal pain, and evidence of gastrointestinal tract ulceration, similar to inflammatory bowel disease. 1,12 Symptom onset ranges from 6 weeks to several months after initial CPI administration.…”

Controversies About COVID-19 and Anticancer Treatment with Immune Checkpoint Inhibitors

“…The second concern seems to be represented by a possible negative interference of ICI in the pathogenesis of COVID-19. Cytokine-release syndrome (CRS) is a phenomenon of immune hyperactivation typically described in the setting of T cell-engaging immunotherapy, including CAR-T cell therapy but also anti-PD-1 agents [15]. CRS is characterized by elevated levels of IL-6, IFN-γ and other cytokines, provoking consequences and symptoms related to immune activation, ranging from fever, malaise and myalgias to severe organ toxicity, lung failure and death.…”

Cellular therapy: Immune‐related complications

“…Cytokine Release Syndrome is not unique to CAR‐T, though its manifestations are generally more severe after CAR‐T infusion. CRS has previously been seen in other cellular and immunotherapies including haploidentical hematopoietic stem cell transplant, checkpoint inhibitors (PD‐1/PD‐L1), BiTEs and other therapies that activate the immune response . The severity of CRS after CAR‐T however has necessitated novel and unique approaches to treatment.…”

“…CRS has previously been seen in other cellular and immunotherapies including haploidentical hematopoietic stem cell transplant, checkpoint inhibitors (PD-1/PD-L1), BiTEs and other therapies that activate the immune response. [54][55][56][57] The severity of CRS after CAR-T however has necessitated novel and unique approaches to treatment. Even within the realm of CAR-T, CRS manifests with different time courses and severity based on the CAR-T construct, tumor type and patient co-morbidities.…”