Grading systems used to score 2 common toxicities for chimeric antigen receptor T-cell (CAR-T) therapy — cytokine release syndrome (CRS) and immune effector cells associated neurotoxicity syndrome (ICANS) — may yield conflicting results, according to a study abstract reported at the 2020 Transplantation & Cellular Therapy Meetings of ASTCT and CIBMTR, held in February 2020 in Orlando, Florida.

The study included 3 sets of patients who received different forms of CD19-directed CAR-T therapy: 53 patients with B-cell acute lymphoblastic leukemia who received CD19-directed CAR-T during a clinical trial ( Identifier: NCT01044069), 36 patients with diffuse large B-cell lymphoma (DLBCL) who received axicabtagene ciloleucel after approval by the U.S. Food and Drug Administration (FDA), and 13 patients with DLBCL who received tisagenlecleucel after approval by the FDA.

Toxicities were graded retrospectively using the new the American Society for Transplantation and Cellular Therapy (ASTCT) system and were compared with the results from existing grading systems. For CRS, the grading systems known as the Lee criteria, the Penn criteria (coming out of University of Pennsylvania), the system from Memorial Sloan Kettering Cancer Center, on CAR toxicity (CARTOX), and the common terminology criteria for adverse events version 5 (CTCAE v5.0) were used, and for ICANS, the grading systems CTCAE v4.03 and CARTOX were used.

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Overall, grading systems showed 99% agreement for diagnosing CRS and 91% agreement for diagnosing ICANS. Grading systems, however, lacked agreement: there was 27% agreement for identifying the same grade of CRS and 55% agreement for identifying the same grade of ICANS. 

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The study researchers also compared the medications patients received at Memorial Sloan Kettering Cancer Center to manage toxicities with the recommended practice from the guidelines or from the US Food and Drug Administration (FDA) label. They found that while the proportion of patients who received tocilizumab (58%) or steroids (13%) was similar to the guideline recommendations and FDA-approved drug label recommendation for axicabtagene ciloleucel, it differed from the drug label recommendation for tisagenlecleucel. Under the drug label recommendation for tisagenlecleucel, 10% would have received tocilizumab and 5% would have received steroids.  

“Indications for treatment vary across current guidelines, which were developed on single products and different grading systems, thus, should not be universally applied,” the study authors wrote. “Different grading systems provide inconsistent CRS/ICANS scores. To avoid discrepancies in assessing and managing toxicities of different products, a unified grading should be used and paired management guidelines with product-specific indications should be developed.”


Pennisi M, Jain T, Mead E, et al. Comparing CAR T cells toxicities grading systems: Application of ASTCT grading system and implications for management. Presented at: the 2020 Transplantation & Cellular Therapy Meetings of ASTCT and CIBMTR; February 19–23, 2020; Orlando, FL. Abstract 51.