ASCO Perspective  
  “A 99% complete response rate for these patients is quite impressive and outcomes at one year are extremely encouraging. Equally impressive is the clinicians’ ability to treat over 200 patients in a short period of time during the COVID-19 pandemic and their ability to manufacture CAR T-cells quickly from a simple blood collection,” said Stephen P. Hunger, MD, ASCO Expert.  

 ALEXANDRIA — In the largest study to date of chimeric antigen receptor (CAR) T-cell therapy for relapsed and refractory childhood B-cell acute lymphoblastic leukemia (B-ALL), clinicians in China were able to rapidly produce dual CD19/CD22 targeted T-cells, resulting in treatments that led to undetectable disease in 99% of 194 patients with treatment-resistant or high-risk-of-relapse leukemia, according to a study published today in the Journal of Clinical Oncology.   

 Study at a Glance    

ALL is the most common of childhood cancers. The disease has a 5-year survival rate of 89% for people under age 20 with current treatments¹. This trial focused on the small subset of patients with B-ALL for whom cancer was resistant to treatment or had returned more than once after treatment.   

In an innovative approach, after a simple blood draw, CAR T cells were engineered in an average of seven days from enrollment to cell infusion. This contrasts with the more common CAR T-cell production process, which typically takes a month and includes freezing and thawing of the cells, which can decrease their activity.  

For each patient the investigators generated CD19-targeted and CD22-targeted CAR T cells independently and then infused them together to target two B-cell antigens simultaneously. Most CAR-T therapies only target one antigen. The clinicians hypothesized that the combination therapy could slow or stop the development of drug resistance as a preclinical model showed simultaneous targeting may reduce the risk of relapse after antigen loss.   

“We believe that this regimen may become the new standard of care, in part because it spares some patients from the use of local radiation to the bone marrow, the testes or the central nervous system, which can cause life-altering side effects, such as sterilization, severe neuro-cognitive impairment, and brain tumors,” said corresponding author Ching-Hon Pui, MD, Departments of Oncology, Pathology and Global Pediatric Medicine, St. Jude Children’s Research Hospital, Memphis, TN. “To put this study in context, the first child who received CAR T-cell therapy for B-ALL after multiple relapses has recently celebrated her 10-year cancer-free survival milestone, and we hope that our finding will result in many more such milestones.”  

Key Findings   
Complete remission was achieved in 99% of the 194 patients with treatment-resistant leukemia or a reappearance of leukemia cells. The combined overall 12-month event-free survival was 73.5%. Relapse occurred in 43 patients.  

The site-specific 12-month event-free survival rate in the trial was 69.2% in children treated with CD19- and CD22-CAR T-cell therapy without a transplant of healthy stem cells from a donor, 95% for those children who had an isolated return of the disease to the testicles and 68.6% for those who had an isolated central nervous system relapse.  

Next Steps
Some patients experienced a loss of CD19- and CD22-CAR T–cell response. The researchers believe that CD22-CAR T cells did not expand as robustly and did not persist as long as CD19-CAR T cells. They hope that future studies will determine whether enhancing CD22-CAR T-cell persistence and activity would improve outcomes. They also note that the number of testicular cases in this trial was relatively small and that future studies are warranted to determine the biological basis of the outcome and confirm why the testicular response rate was higher than what was found in children in whom cancer had returned to other parts of the body.  

^[1] Cancer.Net: ALL statistics: https://www.cancer.net/cancer-types/leukemia-acute-lymphocytic-all/statistics

View disclosures for Dr. Hunger 

Disclosures for the study authors can be found in the full study.  

ATTRIBUTION TO THE JOURNAL OF CLINICAL ONCOLOGY IS REQUESTED IN ALL COVERAGE.