New Paper Explores the Application of ASTCT’s Grading System and Implications for Management of CAR T-cell Toxicity

A new paper published in Blood Advances compares ASTCT’s CAR T-cell toxicity grading system to other available ones, and finds the need for a universal grading system to be used across clinical trials and in clinical practice, paired with management guidelines with product-specific indications. Furthermore, it suggests ASTCT’s system should be the unifying system.

The paper “Comparing CAR T-Cell Toxicity Grading Systems: Applications of the ASTCT Grading System and Implications for Management” was published from one of the world’s leading BMT and cellular therapy institutions. In it, Dr. Martina Pennisi and her colleagues examined different grading systems for CAR-T toxicities. They found that while there are several different types of grading systems, they vary by toxicity profile and by product.

Researchers looked at 102 patients who experienced cytokine release syndrome (CRS) or immune effector cell-associated neurotoxicity syndrome (ICANS) after being treated with either 1928z CAR T-cells (for b-cell acute lymphoblastic leukemia), axicabtagene-ciloleucel or tisagenleleucel (for diffuse large B-cell lymphoma). They found each method they examined for measuring CRS or ICANS differed slightly from ASTCT’s model. Depending on the treatment guidelines clinicians used, this could result in overtreatment or undertreatment of toxicities, depending on the type of model used.

ASTCT’s grading system “proved to be easily applicable,” researchers wrote, and it largely reproduced the incidence of toxicities previously reported in clinical trials. They recommended using ASTCT’s grading system as a unifier, and that more study needs to be done regarding CRS- and ICANS-specific treatment. Doing this would ensure a standardized system, which would help appropriately determine treatment and eliminate the general confusion that exists with several different types of systems.

Dr. Miguel Perales, Deputy Chief of the Adult Bone Marrow Transplantation Service at Memorial Sloan Kettering and senior author of the study, made the following comment: “We designed this study to assess how the new ASTCT consensus grading compared to previously used systems and showed that a uniform grading system was needed to be able to compare side effects across studies and in different patient populations.  Furthermore the use of multiple different systems in patients treated in a single clinical unit and the existence of multiple treatment guidelines could expose patients to delayed treatment or over treatment.”


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