CAR T-Cell Combination Demonstrates Efficacy in Pediatric Patients With B-ALL


Treatment with CD19-/CD22-chimeric antigen T-cell therapy demonstrated durable remissions in children with relapsed or refractory B-acute lymphoblastic leukemia, according to a phase 2 study.

A new immunotherapy combination using 2 types of chimeric antigen receptor (CAR) T cells led to remissions in 99% of pediatric patients with relapsed B-cell acute lymphoblastic leukemia (ALL).1

The findings of this study between St. Jude Children’s Research Hospital and Shanghai Children’s Medical Center were published in November 2022 in the Journal of Clinical Oncology.

Among the 225 patients enrolled in the study, results showed that at 12 months following treatment, approximately 3/4 did not experience another relapse.

“We have learned that you must hit the cancer cells with combination therapies with different mechanisms of action at the same time to cure patients,” said Ching-Hon Pui, MD, chair of the St. Jude Department of Oncology, in the press release.

This study builds upon research started by St. Jude 60 years ago. During this time, doctors on the Memphis campus used a combination of chemotherapies to treat pediatric patients with ALL, leading to substantially higher survival rates in this patient population.

In this recent study, investigators used a similar treatment approach consisting of 2 types of CAR T cells, CD19- and CD22-, to treat the toughest cases of relapsed B-ALL. The phase 2, retrospective study included 225 evaluable patients who were 20 years or younger. Patients were treated at 5 urban hospitals in and near Shanghai, China.

Among those enrolled, 194 patients had refractory disease or hematologic relapse, and 31 patients had isolated extramedullary relapse.

Those involved in the study were also interested in using CAR T cells to treat patients with extramedullary relapse (EMR) as it is a common practice to use radiation to treat EMR and linked with adverse events, including development of a secondary brain tumor, neurocognitive problems and restricted growth among patients treated for central nervous system relapse, and sterility among those treated for testicular relapse.

While CAR T cell preparation used to take over a month, investigators in this study saw advances in the timing and were able to create the necessary CAR T cells in just 1 week.

“Because our CAR T-cell preparation can be done quickly, the patients received the treatment in good clinical condition,” said Pui. “For other approaches, you need to give the patient additional chemotherapy to prevent the progression of the disease and try to keep the patient in good shape for 35 to 40 days to prepare the CAR T cells. The patient may become too sick or have too many leukemia cells before they receive CAR-T cell treatment. This faster approach offers a big advantage.”

Initially, a safety run-in stage was conducted to determine the recommended dose. Then, an interim analysis was performed and showed that of the first 30 patients who were treated (27 at the recommended dose) the approach was safe and effective. The study then enrolled additional patients.2

Findings showed that 192 of 194 patients (99%) who achieved complete remission attained negative minimal residual disease status. At 12 months, their overall event-free survival (EFS) was 73.5% (95% CI, 67.3-80.3). At a median follow-up of 11 months, 43 patients experienced relapse, including CD191/CD221 relapse (n = 24), CD19- /CD221 (n = 16), CD19- /CD22- (n = 1), and unknown (n = 2), for a cumulative risk of 22.2%. Additionally at 6 months, consolidative transplantation and persistent B-cell aplasia were associated with favorable outcomes.

For the 78 patients treated with transplantation, the 12-month EFS was 85.0% (95% CI, 77.2-93.6) while it was 69.2% (95% CI, 60.8-78.8) for the 116 non-transplanted patients (P = .03). All patients with persistent B-cell aplasia (n = 25) at 6 months remained in remission at 12 months.

The 12-month EFS for the 20 patients with isolated testicular relapse was 95.0% (95% CI, 85.9-100). Then for the 10 patients with isolated CNS relapse, 12-month EFS was 68.6% (95% CI, 44.5-100). Regarding safety, cytokine release syndrome was observed in 198 (88.0%) patients, and CAR T-cell neurotoxicity was seen in 47 (20.9%). This resulted in 3 deaths.

Overall, these data show that treatment with CD19-/CD22-CAR T-cell therapy led to relatively durable remission in pediatric patients with relapsed or refractory B-ALL, including patients with isolated or combined EMR.

“This research is evidence of what we can accomplish together and is just the latest example of scientific discoveries our teams can achieve,” added Carlos Rodriguez-Galindo, MD, chair of the St. Jude Department of Global Pediatric Medicine. “The results of this study will bring hope and options for cure to children with refractory leukemia all over the world.”

  1. New study achieves 99 percent remission in children who relapse with most common childhood cancer. News release. St. Jude. December 16, 2022. Accessed December 20, 2022.
  2. Wang T, Tang Y, Cai J, et al. Coadministration of CD19- and CD22-Directed Chimeric Antigen Receptor T-Cell Therapy in Childhood B-Cell Acute Lymphoblastic Leukemia: A Single-Arm, Multicenter, Phase II Trial [published online ahead of print, 2022 Nov 8]. J Clin Oncol. 2022;JCO2201214. doi:10.1200/JCO.22.01214
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