CAR T-cell therapy involves removing patient T cells, re-engineering them, and introducing them back into the body, where they attack cancer cells. The FDA approved the first CAR T-cell therapy for children and young adults with ALL last year. Ongoing research aims to expand its use for other cancers.
“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, M.D., associate professor of Pediatrics and Chief of Pediatric Stem Cell Transplant and Cellular Therapy at MD Anderson. “This novel therapy requires the medical vigilance of a diverse multi-disciplinary team and associated clinical infrastructure to ensure optimal patient outcomes.”
As CAR T-cell therapy becomes more widely used, treatment guidelines, comprehensive training of multi-disciplinary staff, and other measures should facilitate the appropriate management of toxicities that may occur following this new treatment, added Mahadeo.
MD Anderson’s CAR T-cell-therapy-associated Toxicity (CARTOX) program collaborated with PALISI and its Hematopoietic Stem Cell Transplantation (HSCT) sub-group in creating the comprehensive guidelines for treating children with cancer receiving CAR T-cell therapy. By bringing together experts from many areas, including pediatric intensivists, pharmacy, neurology, and translational immunotherapy research, the guidelines offer key learnings to providers and aim to help improve the patient experience and outcome.
In 2017, MD Anderson’s CARTOX Program published guidelines in Nature Reviews Clinical Oncology on management of adult patients receiving CAR T-cell therapy. However, early signs and symptoms of toxicity in children brought attention to pediatric-specific monitoring including escalation of care based on parent and caregiver concerns.
Some examples of the recommendations include:
Monitoring for cytokine release syndrome (CRS) using pediatric normal ranges for organ function.
Promptly addressing parent and/or caregiver concerns as early signs or symptoms of CRS can be subtle and best recognized by those who know the child best.