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

Dristhi Ragoonanan, Sajad J. Khazal, Hisham Abdel-Azim, David McCall, Branko Cuglievan, Francesco Paolo Tambaro, Ali Haider Ahmad, Courtney M. Rowan, Cristina Gutierrez, Keri Schadler, Shulin Li, Matteo Di Nardo, Linda Chi, Alison M. Gulbis, Basirat Shoberu, Maria E. Mireles, Jennifer McArthur, Neena Kapoor, Jeffrey Miller, Julie C. FitzgeraldPriti Tewari, Demetrios Petropoulos, Jonathan B. Gill, Christine N. Duncun, Leslie E. Lehmann, Sangeeta Hingorani, Joseph R. Angelo, Rita D. Swinford, Marie E. Steiner, Fiorela N. Hernandez Tejada, Paul L. Martin, Jeffery Auletta, Sung Won Choi, Rajinder Bajwa, Natalie Dailey Garnes, Partow Kebriaei, Katayoun Rezvani, William G. Wierda, Sattva S. Neelapu, Elizabeth J. Shpall, Selim Corbacioglu, Kris M. Mahadeo

Research output: Contribution to journalReview articlepeer-review

Abstract

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.

Original languageEnglish (US)
JournalNature Reviews Clinical Oncology
DOIs
StateAccepted/In press - 2021
Externally publishedYes

Bibliographical note

Funding Information:
C.G. has served on the advisory board for Janssen and Legend Biotech. A relative of J.B.G. is a consultant to Acceleron and Celgene. K.R. and E.J.S. have a licence agreement with Takeda. E.J.S. has served on the advisory boards of Adaptimmune, Axio, Bayer, Celgene, Magenta, Mesoblast and Novartis. K.M.M. serves as a site investigator for, receives research funding from and has served as a medical consultant for Atara Biotherapeutics, and has received research and medical education funds from and served as a medical consultant for Jazz Pharmaceuticals. All other authors declare no competing interests.

Funding Information:
We thank the MD Anderson Cancer Center CAR T Cell Therapy-Associated Toxicity (CARTOX) Program, The University of Texas MD Anderson Cancer Center, the Pediatric Acute Lung Injury and Sepsis Investigators (PALISI) Network Hematopoietic Cell Transplantation-Cancer Immunotherapy (HCT-CI) Subgroup and the PALISI Network Scientific Committee, the Supportive Care Committee of the Pediatric Transplantation and Cellular Therapy Consortium (PTCTC), the Extracorporeal Life Support Organization (ELSO) and the Paediatric Diseases Working Party (PDWP) of the European Society of Blood and Marrow Transplantation (EBMT). D.R., S.J.K., D.McC., B.C., B.S., J.M., P.T., D.P., F.N.H.T., P.K., K.R., S.S.N, E.J.S. and K.M.M. are members of the CARTOX Program. H.A, A.H.A., M.D.N., B.S., M.E.S. and K.M.M. are members of the PALISI HCT–CI subgroup. H.A.A., J.A., S.W.C. and K.M.M are members of the PTCTC. M.D.N. is a member of ELSO. S.C. is a member of the PDWP of the EBMT. We thank our patients and families who inspire and guide us towards continuous improvement. We thank our respective nursing unit staffs and key stakeholders who work to ensure access to novel therapies for our patients. C.M.R. is the recipient of a K23 grant (1K23HL150244) from the National Heart, Lung and Blood Institute.

Publisher Copyright:
© 2021, The Author(s).

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