Researchers from the University of Texas MD Anderson Cancer Center, along with the Pediatric Acute Lung Injury and Sepsis Investigators Network (PALISI), recently published guidelines in Nature Reviews Clinical Oncology for the management of chimeric antigen receptor (CAR) T-cell therapy for children with acute lymphoblastic leukemia.
Researchers from the University of Texas MD Anderson Cancer Center, along with the Pediatric Acute Lung Injury and Sepsis Investigators Network (PALISI), recently published guidelines1 in Nature Reviews Clinical Oncology for the management of chimeric antigen receptor (CAR) T-cell therapy for children with acute lymphoblastic leukemia (ALL).
Although CAR T-cell therapy has shown largely positive results in both hematological and nonhematological malignancies, it has also been associated with unique acute toxicities, such as cytokine-release syndrome (CRS), which can be severe or even fatal. The guidelines look to summarize lessons learned by experts in various fields in regard to identifying early signs and symptoms of treatment-related toxicity and ways to manage it.
“CAR T-cell therapy has been associated with remarkable response rates for children and young adults with ALL, yet this innovative form of cellular immunotherapy has resulted in unique and severe toxicities which can lead to rapid cardiorespiratory and/or neurological deterioration,” said Kris Mahadeo, MD, associate professor of pediatrics and chief of Stem Cell Transplant and Cellular Therapy at MD Anderson, in a statement.
MD Anderson’s CAR T-cell therapy—associated Toxicity (CARTOX) program collaborated with PALISI and its Hematopoietic Stem Cell Transplantation subgroup in the creation of the guidelines. The joint effort brought together experts from a multitude of fields, including pediatric intensivists, pharmacy, neurology, and translational immunotherapy research, and looked to improve the patient experience and outcomes.
Some key recommendations include:
These guidelines act as a follow-up to the guidelines previously published in 2017 in Nature Reviews Clinical Oncology on the management of adult patients receiving CAR T-cell therapy. However, given the early signs and symptoms of toxicity in children and how quickly deterioration can happen, researchers saw the need for pediatric-specific monitoring guidelines, including the escalation of care based on parent and caregiver concerns.
1. Mahadeo K, Khazal S, Abdel-Azim H, et al. Management guidelines for pediatric patients receiving chimeric antigen receptor T cell therapy [published online August 6, 2018]. Nat Rev Clin Oncol. doi: 10.1038/s41571-018-0075-2.
2. Neelapu S, Tummala S, Kebriaei P, et al. chimeric antigen receptor T-cell therapy—assessment and management of toxicities. Nat Rev Clin Oncol. 2018;15:47-62. doi: 10.1038/nrclinonc.2017.148.