Tumor inflammation-associated neurotoxicity.

Publication Year:

2023

Authors:

Jasia Mahdi, Jorg Dietrich, Karin Straathof, Claire Roddie, Brian J Scott, Tom Belle Davidson, Laura M Prolo, Tracy T Batchelor, Cynthia J Campen, Kara L Davis, Juliane Gust, Michael Lim, Robbie G Majzner, Julie R Park, Sonia Partap, Sneha Ramakrishna, Rebecca Richards, Liora Schultz, Nicholas A Vitanza, Leo D Wang, Crystal L Mackall, Michelle Monje

PubMed ID:

37024595

Funding Grants:

Phase I Study of IL13Rα2-Targeting CAR T Cells After Lymphodepletion for Children with Refractory or Recurrent Malignant Brain Tumors

Public Summary:

Cancer immunotherapies have unique toxicities, and establishing toxicity grading scales and standardized grade-based treatment algorithms can improve the safety of these treatments. We have observed a toxicity syndrome, distinct from the more commonly observed cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome (ICANS), in patients treated with cell therapies for tumors in the central nervous system (CNS), which we term tumor inflammation-associated neurotoxicity (TIAN). TIAN is relevant not only to cellular therapies, but also to other immunotherapies for CNS tumors. To facilitate the safe administration of cell therapies for patients with CNS tumors, we define TIAN, propose a toxicity grading scale for TIAN syndrome and discuss the potential management of TIAN, with the goal of standardizing both reporting and management.

Scientific Abstract:

Cancer immunotherapies have unique toxicities. Establishment of grading scales and standardized grade-based treatment algorithms for toxicity syndromes can improve the safety of these treatments, as observed for cytokine release syndrome (CRS) and immune effector cell associated neurotoxicity syndrome (ICANS) in patients with B cell malignancies treated with chimeric antigen receptor (CAR) T cell therapy. We have observed a toxicity syndrome, distinct from CRS and ICANS, in patients treated with cell therapies for tumors in the central nervous system (CNS), which we term tumor inflammation-associated neurotoxicity (TIAN). Encompassing the concept of 'pseudoprogression,' but broader than inflammation-induced edema alone, TIAN is relevant not only to cellular therapies, but also to other immunotherapies for CNS tumors. To facilitate the safe administration of cell therapies for patients with CNS tumors, we define TIAN, propose a toxicity grading scale for TIAN syndrome and discuss the potential management of this entity, with the goal of standardizing both reporting and management.