Profound Epistaxis in Cytokine Release Syndrome Following Chimeric Antigen Receptor T-Cell Therapy

ABSTRACT

INTRODUCTION: Chimeric antigen receptor T-cells (CAR-T) represent a promising immunotherapeutic approach in the treatment of refractory malignancies, but carry the risk of unique inflammatory toxicities including cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome (ICANS). In moderate to severe cases, these toxicities necessitate intensive care unit (ICU) admission for aggressive support and management. DESCRIPTION A 63-year-old male with a history of pulmonary embolism, prostate cancer with resection and relapsed/refractory IgG-kappa multiple myeloma (diagnosed 4 years earlier and status-post multiple chemotherapy regimens) was admitted for conditioning chemotherapy and CAR-T cell infusion. 1 day post-infusion on the ward, he developed CRS and ICANS, with fever and altered mental status, for which he received tocilizumab, dexamethasone, and anakinra, in addition to empiric antibiotics. He progressed with worsening hypotension and encephalopathy and was admitted to the ICU and required vasopressors, pulse-dose steroids, and siltuximab. A nasal swab was performed to rule out COVID-19, following which he developed persistent epistaxis, requiring packing and, after aspiration of blood, intubation for airway protection. Laboratory data showed anemia and thrombocytopenia, prolonged PT and aPTT, low fibrinogen, and elevated levels of ferritin of 44,124 mg/ mL, D-Dimer of 1.35 mug/mL, interleukin-6 of 8,595 pg/ mL, interleukin-10 of 1,042 pg/mL, tumor necrosis factor- alpha of 103 pg/mL, and interferon-gamma above 244 pg/mL. The patient received numerous red cell and platelet transfusions, aminocaproic acid, cryoprecipitate, and additional packing and thrombin application by ENT before his epistaxis was controlled. Ultimately, he was weaned from vasopressors, extubated after two weeks and transferred out of the ICU, discharged to rehabilitation, and later home. DISCUSSION: Severe CRS can be associated with hemophagocytic lymphohistiocytosis and disseminated intravascular coagulation (DIC), which can lead to lifethreatening bleeding as demonstrated in our patient. Effective and timely treatment of bleeding associated with DIC and severe CRS can be life-saving. It behooves the intensivist to recognize the toxicities of CAR-T as therapeutic applications broaden in the coming years.