Tumor inflammation-associated neurotoxicity

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

doi:10.1038/s41591-023-02276-w

Tumor inflammation-associated neurotoxicity

Nat Med. 2023 Apr;29(4):803-810. doi: 10.1038/s41591-023-02276-w. Epub 2023 Apr 6.

Authors

Jasia Mahdi^{1

2}, Jorg Dietrich³, Karin Straathof⁴, Claire Roddie⁴, Brian J Scott¹, Tom Belle Davidson⁵, Laura M Prolo⁶, Tracy T Batchelor^{7

8}, Cynthia J Campen¹, Kara L Davis^{2

9}, Juliane Gust^{10

11}, Michael Lim⁶, Robbie G Majzner^{2

9}, Julie R Park^{12

13}, Sonia Partap^{1

6

9}, Sneha Ramakrishna^{2

9}, Rebecca Richards^{2

9}, Liora Schultz^{2

9}, Nicholas A Vitanza^{12

13}, Leo D Wang¹⁴, Crystal L Mackall^{15

16

17}, Michelle Monje^{18

19

20

21

22

23}

Affiliations

¹ Department of Neurology and Neurological Sciences, Stanford University, Stanford, CA, USA.
² Stanford Center for Cancer Cell Therapy, Stanford University School of Medicine, Stanford, CA, USA.
³ Department of Neurology, Massachusetts General Hospital, Boston, MA, USA.
⁴ Research Department of Hematology and Oncology, Cancer Institute, University College London, London, UK.
⁵ Cancer and Blood Disease Institute, Children's Hospital Los Angeles, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA.
⁶ Department of Neurosurgery, Stanford University, Stanford, CA, USA.
⁷ Department of Neurology, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, USA.
⁸ Dana-Farber/Harvard Cancer Center, Harvard Medical School, Boston, MA, USA.
⁹ Department of Pediatrics, Stanford University, Stanford, CA, USA.
¹⁰ Department of Neurology, University of Washington, Seattle, WA, USA.
¹¹ Seattle Children's Research Institute, Center for Integrative Brain Research, Seattle, WA, USA.
¹² Department of Pediatrics, Seattle Children's Hospital, University of Washington, Seattle, WA, USA.
¹³ Ben Towne Center for Childhood Cancer Research, Seattle Children's Research Institute, Seattle, WA, USA.
¹⁴ City of Hope, Departments of Pediatrics and Immuno-oncology, Beckman Research Institute, City of Hope National Medical Center, Duarte, CA, USA.
¹⁵ Stanford Center for Cancer Cell Therapy, Stanford University School of Medicine, Stanford, CA, USA. cmackall@stanford.edu.
¹⁶ Department of Pediatrics, Stanford University, Stanford, CA, USA. cmackall@stanford.edu.
¹⁷ Department of Medicine, Stanford University School of Medicine, Stanford, CA, USA. cmackall@stanford.edu.
¹⁸ Department of Neurology and Neurological Sciences, Stanford University, Stanford, CA, USA. mmonje@stanford.edu.
¹⁹ Stanford Center for Cancer Cell Therapy, Stanford University School of Medicine, Stanford, CA, USA. mmonje@stanford.edu.
²⁰ Department of Neurosurgery, Stanford University, Stanford, CA, USA. mmonje@stanford.edu.
²¹ Department of Pediatrics, Stanford University, Stanford, CA, USA. mmonje@stanford.edu.
²² Department of Pathology, Stanford University, Stanford, CA, USA. mmonje@stanford.edu.
²³ Howard Hughes Medical Institute, Stanford University, Stanford, CA, USA. mmonje@stanford.edu.

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.

Publication types

Review
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't

MeSH terms

Cytokine Release Syndrome / etiology
Cytokine Release Syndrome / therapy
Humans
Immunotherapy
Immunotherapy, Adoptive / adverse effects
Inflammation
Neoplasms* / therapy
Neurotoxicity Syndromes* / etiology

Abstract

Publication types

MeSH terms

Grants and funding