(224) Taking a BiTE® into CRS Management: Cytokine Release Syndrome Management for Bispecific T Cell Engager Therapies

Poster Abstract:

Background: Immunotherapies such as chimeric antigen receptor (CAR) T-cell therapies and bispecific T-cell engagers (BiTE®) are rapidly transforming cancer therapy. Unfortunately, they contain boxed warnings for cytokine release syndrome (CRS), a systemic inflammatory response characterized by hypersecretion of pro-inflammatory cytokines. In 2019, the American Society for Transplantation and Cellular Therapy (ASTCT) released a consensus guideline for CRS associated with CAR T and recommended tocilizumab treatment for CRS, while reserving corticosteroids for CRS refractory to IL-6 blockade. Despite many similarities between CAR T and BiTE®, the presentation of CRS differs between the two. All BiTE® therapy package inserts recommend withholding treatment until resolution of CRS; however, further management with tocilizumab and/or corticosteroids is variable. Due to lack of standardized protocols, providers often manage based on the aforementioned CAR T CRS guidelines, medication package inserts, or a combination of these approaches, which can lead to inconsistent practice.

Objectives: This quality improvement project aims to characterize Froedtert & the Medical College of Wisconsin’s (FMCW) current approach to the management of CRS in patients receiving BiTE® therapies and create an institutional guideline to standardize treatment. Secondary objectives include assessment of immune effector cell-associated neurotoxicity syndrome (ICANS) management, incidence of CRS and ICANS, length of stay, incidence of transfer to intensive care, and evaluation of mortality 90 days post first BiTE® dose.

Methods: Retrospective chart review was completed for patients 18 years or older who received at least one dose of tebentafusp, teclistamab, mosunetuzumab, epcoritamab, glofitamab, or talquetamab and were admitted to FMCW for administration and/or CRS management between January 1, 2022 and October 31, 2023. Patients were excluded if they received an investigational BiTE® or drug administration deviated from dosing escalation as recommended by the package insert.

Results: Preliminary results include 69 encounters with 30 cases of CRS. Of these 30 cases, 22 patients received tocilizumab, 28 received antibiotics, and 5 received steroids in the setting of refractory CRS.

Discussion/

Conclusion: Based on preliminary results, most patients received tocilizumab for management of CRS, aligning with FMCW’s current guideline for the management of CRS from CAR T therapies. Currently, the Food and Drug Administration (FDA) classifies tocilizumab for CRS management with BiTE® agents as a category C recommendation, limiting its Medicare coverage in the outpatient setting. As BiTE® administration migrates to the outpatient setting, there may be limitations to tocilizumab coverage, preventing its use and creating a barrier to CRS management.

References (must also be included in final poster): 1. Teclistamab. Hudson, OH: Lexicomp. https://online.lexi.com/. Updated July 5, 2023. Accessed July 5, 2023.
2. Mosunetuzumab. Hudson, OH: Lexicomp. https:online.lexi.com. Updated May 30, 2023. Accessed July 3, 2023.
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