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CD19/CD22-Targeted CAR-T Cell Therapy Achieves Durable Remission in Children With B-ALL

Key Takeaways

  • Bicistronic CD19/CD22 CAR-T therapy shows high efficacy in pediatric B-ALL, with a 99.1% response rate and significant survival outcomes.
  • Consolidative transplantation post-CAR-T therapy enhances EFS but does not significantly impact OS in patients with hematologic relapse.
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This builds off prior data that showed safety and efficacy of CD19 and CD22 chimeric antigen receptor (CAR)-T cell therapy in children with relapsed or refractory B-lineage acute lymphoblastic leukemia (B-ALL).

Bicistronic CD19 and CD22 chimeric antigen receptor (CAR)-T cell therapy is safe and effective in children with relapse or refractory B-lineage acute lymphoblastic leukemia (B-ALL), said Hua Zhang, MD, PhD, VP and chief scientific officer at SPH Biotherapeutics, in a 2024 American Society of Hematology (ASH) Annual Meeting and Exposition presentation. According to Zhang, the research built off data from a previous 2023 study published in Journal of Clinical Oncology which also showed efficacy in children with B-ALL.

Leukemia cells in bloodstream -- Image credit: Nicat | stock.adobe.com

Image credit: Nicat | stock.adobe.com

For this investigator-initiated trial, the authors aimed to further improve outcomes and enhance event-free survival (EFS) and overall survival (OS) in young patients with B-ALL with bicistronic CD19/CD22 CAR-T cell therapy. A total of 318 patients aged 18 and younger with or without consolidative allogenic transplant following CAR-T therapies were enrolled between January 2022 and April 2024. The investigators assessed patients’ clinical responses, adverse events (AEs) and the expansion and persistence of CAR-T cells.

“After patients [were] enrolled, we collected the blood, [performed] the CAR T-cell manufacturing, [and] in the meantime, we [did a] preparation regimen on day 0,” explained Zhang. “We started to infuse the CAR T-cells, and we [performed] the follow-up to measure the CAR T expansion, checked the cytokine production, and also did bone marrow biopsies.”

Among the enrolled patients, 51 had isolated extramedullary relapse (isolated central nervous system leukemia [CNSL]: n = 28; isolated testicular relapse: n = 21; and other: n = 2), and the remaining 292 had isolated or combined hematologic relapse (isolated bone marrow: n = 203; bone marrow and CNSL: n = 72; and bone marrow and testicular: n = 17). Of the 292 patients with isolated or combined hematologic relapses, 37 underwent subsequent transplantation, of which 13 were recommended per protocol criteria.

The median follow-up for patients who were alive at the time of analysis was about 13.9 months (IQR: 9.0-22.4 months). The investigators observed a response rate of approximately 99.1% among the 318 patients, all of whom were measurable residual disease negative. Further, the regimen achieved a double response in the evaluated patients, including those with isolated or combined extramedullary relapse. According to the findings, the 12-month EFS and OS rates for the 267 patients with isolated or combined hematologic relapse were approximately 72.4% and 91.4%, respectively.

Further, receiving consolidative transplantation was associated with favorable outcomes, with patients receiving transplant demonstrating a 12-month EFS of 86.0% compared with 71.4% for those who did not (P = .04). Despite this improvement, transplantation did not provide a significant benefit in OS, with 12-month OS rates of approximately 94.2% for transplanted patients and 92.2% for non-transplanted patients (P = .86).

Among the 230 patients who did not undergo transplantation following CAR T-cell therapy, 69 patients relapsed with different loss of the antigens (CD19+/CD22+: n = 45; CD19-/CD22+: n = 23; and CD19-/CD22-: n = 1). Most of these patients were treated with a second salvaged bicistronic CD19/CD22 CAR-T cell therapy, and complete remissions were achieved again in 35 (97.2%) patients with CD19+/CD22+ antigen loss and 14 (66.7%) with CD19-/CD22+. Approximately 85.7% (n = 42) of the 49 patients who achieved complete remission were still alive in remission for 1.0 to 22.1 months, 30 of whom received consolidative transplantation.

For the 20 patients with isolated testicular relapse, the 12-month EFS and OS rates were about 84.7% and 100.0%, respectively, and for the 29 patients with isolated CNS relapse, the 12-month EFS and OS rates were 71.0% and 96.2%, respectively. Cytokine release syndrome (CRS) developed in all patients, with grade III through IV CRS occurring in 48.7% (n = 155) of patients. Two deaths were observed, according to the investigators. In addition, CAR T-cell neurotoxicity was also observed in about 16.4% (n = 52) of patients.

“In the study, we [observed that] the severity of CRS is not related to the study dose range of infused cells, whereas it was highly correlated with disease burden and CAR-T viability,” said Zhang at the presentation’s conclusion. “[A] phase 1 clinical trial is on the way and we intend to enroll 12 to 18 patients [with B-ALL].”

REFERENCES
Zhang, H. Putting Women & Children First To Optimize Their Hematology Health: Safety and Efficacy of Bicistronic CD19/CD22 CAR T Cell Therapy in Childhood B Cell Acute Lymphoblastic Leukemia. Presented at: American Society of Hematology Annual Meeting and Exposition; San Diego, CA. December 7-10.
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