Experts Join to Release Guidelines for CAR-T Therapy Use in Child Cancer

Management guidelines for the use of chimeric antigen receptor (CAR) T-cell therapy in pediatric patients with acute lymphoblastic leukemia (ALL) were recently published in Nature Reviews Clinical Oncology (2018 Aug 6. Epub ahead of print).

Experts from The University of Texas MD Anderson Cancer Center’s CAR T-cell-therapy-associated Toxicity (CARTOX) program and the Pediatric Acute Lung Injury and Sepsis Investigators Network (PALISI) Hematopoietic Stem Cell Transplantation (HSCT) Subgroup collaborated to provide these comprehensive consensus recommendations for guiding the treatment of pediatric patients with ALL undergoing CAR T-cell therapy.

The autologous CAR T-cell therapy, tisagenlecleucel, was approved by the FDA in 2017 for the treatment of children and young adults with relapsed and/or refractory CD19-positive ALL. According to the guidelines, approximately 50% of patients who receive this drug require rigorous monitoring and critical care support, mainly because of toxicities, such as cytokine­-release syndrome (CRS) and CAR T-cell–related encephalopathy syndrome (CRES).

“CRS and CRES are generally reversible but can be fatal. Paediatric-­specific management guidelines, comprehensive training of interdisciplinary staff, effective communication, and an appropriately phased infrastructure to ensure that adequate resources are available should facilitate the early diagnosis and appropriate management of paediatric patients who develop CRS and/or CRES after receiving CAR T cell therapy as a standard of care or according to a research protocol — and thereby achieve optimal outcomes,” explained Kris M. Mahadeo, MD, The University of Texas MD Anderson Cancer Center, Department of Pediatrics, Stem Cell Transplantation and Cellular Therapy, Houston, and colleagues.

Here we describe a few key recommendations from these management guidelines for pediatric recipients of CAR T-cell therapy:

• Describe the risks and benefits associated with leukapheresis, lymphodepletion, CRS, CRES, bridging chemotherapy, intensive-care support, and anti-IL-6 therapy as part of the patient consent
• Pediatric patients may need a leukapheresis catheter to collect their cells. During pediatric leukapheresis, it is crucial that the patient be monitored closely for hypotension, hypocalcemia, and catheter-related pain, especially if they are too young to verbalize their symptoms (eg, infants)
• For lymphodepletion, selection of a cyclophosphamide-fludarabine regimen is recommended, except for in cases of hemorrhagic cystitis and/or previous resistance to a cyclophosphamide-based regimen
• For patients receiving CAR T-cell therapy in an outpatient setting, set a low threshold for patient admission when a fever and/or signs or symptoms suggestive of CRS and/or CRES occur, because there is potential for rapid clinical deterioration
• Carry out CRS grading at least once every 12 hours; shift to grading CRS more often if a change or concerns arise

“Multidisciplinary medical vigilance and the requisite health-care infrastructure are imperative to ensuring optimal patient outcomes, especially as these therapies transition from research protocols to standard care,” they concluded.—Janelle Bradley