New Guidelines Help Ensure Optimal Outcomes for Children Treated with CAR-T Cell Therapy


CAR-T cell therapy has been showing promising in treating children with acute lymphoblastic leukemia, but it can come with significant toxicities.

While chimeric antigen receptor (CAR)-T cell therapy has demonstrated positive response rates in children with relapsed and/or refractory CD19-positive acute lymphoblastic leukemia (ALL), severe toxicities can also be associated with such treatment. So, a group of researchers issued guidelines to help ensure these patients experience optimal outcomes.

“These guidelines are meant to be a truly comprehensive guide to ensure safe delivery of CAR-T therapy to pediatric patients,” Kris Mahadeo, M.D., associate professor of Pediatrics and chief of Stem Cell Transplant and Cellular Therapy at MD Anderson, said in an interview with CURE.

“This includes recommendations regarding pediatric clinical management algorithms and staff training, infrastructural needs, disaster preparedness and future research needs,” he added. “We also hope that they may help guide payors to ensure children receive adequate supportive care when indicated.”

CAR-T cell therapy involves the removal of a patient’s own T cells that are then re-engineered to find and destroy cancer proteins or targets. After they are re-engineers, these cells are then infused back into the patient’s body, where they attack the cancer cells.

In August of 2017, the Food and Drug Administration (FDA) approved Kymriah (tisagenlecleucel) for the treatment of patients aged 25 years or younger who have B-cell precursor acute lymphoblastic leukemia (ALL) that is refractory or in second or later relapse.

As CAR T-cell therapy becomes more widely used — it has since expanded in to adult patients and other blood cancer types – researchers from at The University of Texas MD Anderson Cancer Center and the Pediatric Acute Lung Injury and Sepsis Investigators Network (PALISI) collaborated to provide an expert consensus on the care for children treated with CAR-T cell therapy.

The collaboration utilized MD Anderson’s CAR-T cell-therapy-associated Toxicity (CARTOX) program and PALISI’s Hematopoietic Stem Cell Transplantation (HSCT) sub-group to create the comprehensive guidelines.

Last year, guidelines were issued for adult patients being treated with CAR-T cell therapy; however, Mahadeo noted there were striking differences between them.

First, the pediatric guidelines addressed the clinical toxicity grading and management of the most notable treatment-related side effects: cytokine release syndrome (CRS) and CAR-T cell-related encephalopathy syndrome (CRES).

In particular, normal ranges of vital signs such as temperature, heart rate or systolic blood pressure in pediatrics are more variable compared to adults as these signs tend to be age dependent. Therefore, cytokine release syndrome (CRS) grading requires attention to normal ranges based on the age of the child, Mahadeo said. “We felt that it was important to explicitly state this in clinical algorithms,” he added.

In addition, CRES should be detected differently in children. For example, screening for a change in an adult patient’s handwriting or in a neuro-assessment score where a patient is required to count backwards in tens would be inefficient for a child from a developmental standpoint. “In lieu, we recommend the use of a validated pediatric delirium tool (CAP-D) for early CRES recognition among children,” Mahadeo explained.

The pediatric guidelines also addressed the following:

  • A call for inclusion of the enrollment of children on clinical trials at the earliest time points possible.
  • Recognition of the critical role parents/caregivers and nurses play in recognizing subtle signs/symptoms of CRS/CRES.
  • Consideration of quality adjusted life year (QALY) in favor of health care coverage for this therapy for children.

“Because children with cancer interface with multiple aspects of the health care system, we hope that these guidelines will facilitate wider education across health care disciplines to ensure early signs/symptoms of toxicity are not missed and prevent medical management errors that could impact the efficacy of CAR-T cell therapies,” Mahadeo said. “We also hope that recommendations regarding economic considerations will benefit patients at large.”

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