Diagnosis, grading and management of toxicities from immunotherapies in children, adolescents and young adults with cancer

Ragoonanan, Dristhi

; Khazal, Sajad J. ; Abdel-Azim, Hisham ; McCall, David

; Cuglievan, Branko ; Tambaro, Francesco Paolo

; Ahmad, Ali Haider

; Rowan, Courtney M. ; Gutierrez, Cristina ; Schadler, Keri ; Li, Shulin ; Di Nardo, Matteo ; Chi, Linda ; Gulbis, Alison M.

; Shoberu, Basirat ; Mireles, Maria E. ; McArthur, Jennifer ; Kapoor, Neena ; Miller, Jeffrey ; Fitzgerald, Julie C. ; Tewari, Priti ; Petropoulos, Demetrios ; Gill, Jonathan B. ; Duncan, Christine N. ; Lehmann, Leslie E. ; Hingorani, Sangeeta ; Angelo, Joseph R. ; Swinford, Rita D. ; Steiner, Marie E. ; Hernandez Tejada, Fiorela N. ; Martin, Paul L. ; Auletta, Jeffery ; Choi, Sung Won ; Bajwa, Rajinder ; Dailey Garnes, Natalie ; Kebriaei, Partow ; Rezvani, Katayoun ; Wierda, William G. ; Neelapu, Sattva S. ; Shpall, Elizabeth J. ; Corbacioglu, Selim ; Mahadeo, Kris M.

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In this Consensus Statement, members from five working groups or societies provide updated comprehensive recommendations to manage toxicities from cancer immunotherapies in children, adolescents and young adults. In their recommendations, they advocate for the adoption of age-based and discipline-specific management criteria, and call for an increased inclusion of young patients with cancer in clinical trials. Cancer immunotherapies are associated with remarkable therapeutic response rates but also with unique and severe toxicities, which potentially result in rapid deterioration in health. The number of clinical applications for novel immune effector-cell therapies, including chimeric antigen receptor (CAR)-expressing cells, and other immunotherapies, such as immune-checkpoint inhibitors, is increasing. In this Consensus Statement, members of the Pediatric Acute Lung Injury and Sepsis Investigators (PALISI) Network Hematopoietic Cell Transplantation-Cancer Immunotherapy (HCT-CI) Subgroup, Paediatric Diseases Working Party (PDWP) of the European Society of Blood and Marrow Transplantation (EBMT), Supportive Care Committee of the Pediatric Transplantation and Cellular Therapy Consortium (PTCTC) and MD Anderson Cancer Center CAR T Cell Therapy-Associated Toxicity (CARTOX) Program collaborated to provide updated comprehensive recommendations for the care of children, adolescents and young adults receiving cancer immunotherapies. With these recommendations, we address emerging toxicity mitigation strategies, we advocate for the characterization of baseline organ function according to age and discipline-specific criteria, we recommend early critical care assessment when indicated, with consideration of reversibility of underlying pathology (instead of organ failure scores) to guide critical care interventions, and we call for researchers, regulatory agencies and sponsors to support and facilitate early inclusion of young patients with cancer in well-designed clinical trials.

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