Grading of cytokine release syndrome associated with the CAR T cell therapy tisagenlecleucel

David Porter, Noelle Frey, Patricia A Wood, Yanqiu Weng, Stephan A Grupp, David Porter, Noelle Frey, Patricia A Wood, Yanqiu Weng, Stephan A Grupp

Abstract

Background: Anti-CD19 CAR T cell therapy has demonstrated high response rates in patients with relapsed or refractory (r/r) B cell malignancies but is associated with significant toxicity. Cytokine release syndrome (CRS) is the most significant complication associated with CAR T cell therapy, and it is critical to have a reproducible and easy method to grade CRS after CAR T cell infusions.

Discussion: The Common Terminology Criteria for Adverse Events scale is inadequate for grading CRS associated with cellular therapy. Clinical experience with the anti-CD19 CAR T cell therapy tisagenlecleucel at the University of Pennsylvania (Penn) was used to develop the Penn grading scale for CRS. The Penn grading scale depends on easily accessible clinical features; does not rely on location of care or quantitation of supportive care; assigns grades to guide CRS management; distinguishes between mild, moderate, severe, and life-threatening CRS; and applies to both early-onset and delayed-onset CRS associated with T cell therapies. Clinical data from 55 pediatric patients with r/r B cell acute lymphoblastic leukemia and 42 patients with r/r chronic lymphocytic lymphoma treated with tisagenlecleucel were used to demonstrate the current application of the Penn grading scale.

Conclusion: We show that the Penn grading scale provides reproducible CRS grading that can be useful to guide therapy and that can be applied across clinical trials and treatment platforms.

Keywords: CAR T cell therapy; Cytokine release syndrome; Safety.

Conflict of interest statement

Ethics approval and consent to participate

The described studies were sponsored and designed by Novartis Pharmaceuticals Corporation and were approved by the institutional review board. Patients or their guardians provided written informed consent or assent.

Consent for publication

Not applicable.

Competing interests

DP received research support from Novartis, served on a scientific advisory board for Servier, and has a patent—CAR T cells to treat CD19+ malignancy with royalties paid by Novartis. NF received research funding from Novartis. YW is a Novartis employee. PW is a Novartis employee and stockholder. SG received grants and personal fees from Novartis and received personal fees from Jazz Pharmaceuticals and Adaptimmune.

Publisher’s Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

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