Real-World Quality and Cost Burden of Cytokine Release Syndrome Requiring Tocilizumab or Steroids during CAR-T Infusion Encounter

Abstract

Introduction Chimeric Antigen Receptor T-cell (CAR-T) Immunotherapy was first approved by the FDA in October 2017 for adult patients with relapsed or refractory large B-cell lymphoma after two or more lines of systemic therapy. CAR-T immunotherapy uses a patient's own T cells and modifies them in a laboratory to recognize and kill the patient's cancer. Cytokine release syndrome is a known serious adverse event after CAR-T infusion which results in symptoms including fever, nausea, headache, and hypotension. Tocilizumab is an anti-IL-6 receptor antagonist approved for the treatment of CRS in CAR-T patients. For patients with Grade III CRS or Grade II with neurotoxicity, tocilizumab plus corticosteroids is indicated for treatment. However, corticosteroids alone can also be used for patients with lower grade neurotoxicity. Objectives To compare cost and quality outcomes for patients with DLBCL who receive a CAR-T infusion with or without tocilizumab or steroids. Methods A retrospective cohort of 1570 CAR-T infusion encounters for patients 18 years and older undergoing CAR-T procedures for DLBCL was identified from the Vizient Clinical Database/Resource Manager from 71 hospitals between October 2017 and July 2019. Patients with a tocilizumab, dexamethasone or prednisolone charge during the infusion encounter were identified through charge data and/or CPT coding. Cost information was analyzed for patients who were not in a clinical trial and who had complete charge information. Results Of the 1570 infusion encounters, 739 patients (47.1%) received tocilizumab during their index visit. 839 patients (53.4%) received a dexamethasone or prednisolone during their index encounter, with 574 (36.6%) of patients receiving both tocilizumab and a corticosteroid. Patients who did not receive steroids or tocilizumab had a lower LOS (14.3 days) compared to patients with steroids (19.4 days), tocilizumab (16.2 days) or tocilizumab+steroids (23.3 days). Patients who did not receive steroids or tocilizumab had the lowest in-hospital mortality rate (1.4%) compared to patients who received steroids (3.4%), tocilizumab (1.8%) or tocilizumab+steroids (8.4%). Patients who did not receive steroids or tocilizumab had the lowest mean cost ($376,982) compared to patients who received steroids ($394,113), tocilizumab ($409,142) or tocilizumab+steroids ($429,415). Conclusion Understanding the risks associated with CAR-T therapy is important. While CRS is a known serious adverse event, characterizing the impact of how CRS affects LOS, in-hospital mortality and cost is important for both providers and patients to assess when deciding which therapies to consider. More severe CRS can lead to longer lengths of stay, higher in-hospital mortality, and higher costs of care.