Children with relapsed or refractory B-cell acute lymphoblastic leukemia (B-ALL) demonstrated high remission rates after treatment with a novel bicistronic CD19/CD22-directed CAR-T cell therapy.
The treatment also generated durable responses and was shown to be safe among these patients, including those with isolated or combined extramedullary relapsed disease, according to updated data from a phase 2 trial presented at the 2024 ASH Annual Meeting.
At a median follow-up of 13.9 months, the one-year event-free survival (EFS) rate was 75.5%, and the one-year overall survival (OS) rate was 93.5% among patients enrolled and treated with bicistronic CD19/CD22-directed CAR-T cell therapy (343 patients).
Following CAR-T cell expansion, the one-year EFS rates among patients who underwent bridging bone marrow transplant (38 patients) versus those who did not (280 patients) were 89.7% versus 76.8%, respectively. The respective one-year OS rates were 95.8% versus 95.2%.
“After CAR-T cell therapy, we have found that the one-year EFS [rate] is higher [with] CAR-T cell treatment plus bone marrow transplant than CAR-T cell treatment alone, [although the] one-year OS [rates were] very similar between these two [populations],” presenting author Dr. Hua Zhang, vice president and chief scientific officer at SPH Biotherapeutics (HK), Limited, stated in an oral presentation of the data during a virtual press briefing.
Most patients developed cytokine release syndrome (CRS); those with lower-grade CRS had better one-year EFS outcomes than those with higher-grade CRS. Among the 172 patients with grade 1 or 2 (mild or moderate) CRS, the one-year EFS rate was 80.9%. The one-year EFS rate for the 145 patients with grade 3 or 4 (severe or life-threatening) CRS was 69.9%.
In the presentation, Zhang added that “in this study, we found the severity of CRS was not related to the study dose range of infused cells, whereas it was highly correlated with disease burden and CAR-T cell viability.”
Complete Responses to CAR-T Cell Therapy in Pediatric B-ALL
Following treatment, complete remission (CR) to treatment was achieved across all patients in the isolated extramedullary relapse cohort. In the refractory, isolated, combined hematologic relapse cohort, all but one patient with isolated bone marrow relapse achieved a CR. This patient died before their evaluation.
A total of 13 and 228 patients in the isolated bone marrow and bone marrow plus testes relapse subgroups, respectively, underwent subsequent transplantation according to protocol criteria. Notably, 25 additional patients in the isolated bone marrow subgroup underwent transplantation according to parental request.
Based on these results, a phase 1 study of the regimen is underway. Investigators on the study plan to enroll 12 to 18 patients in the study.
More About the Phase 2 Trial
Previously reported data from this phase 2 trial showed that co-administration of CD19- and CD22-directed CAR-T cell therapy produced relatively durable EFS rates and a high CR rate among 225 children with relapsed or refractory B-ALL or those at a high risk of hematologic or extramedullary relapse. CR was achieved in 99% of patients (194 patients), all of whom achieved minimal residual disease negativity.
The 12-month EFS rates were 69.2%, 95% and 68.6%for patients treated for hematologic relapse without consolidative allogeneic hematopoietic cell transplantation (allo-HSCT; 116 patients), isolated testicular relapse (two patients) and isolated central nervous system (CNS) relapse (10 patients), respectively.
Accordingly, investigators developed a bicistronic CD19/CD20-directed CAR-T cell therapy to enhance EFS, OS and safety outcomes for patients with relapsed or refractory B-ALL, regardless of prior exposure to consolidative allo-HSCT after CAR-T cell therapy
Reference
“Safety and efficacy of bicistronic CD19/CD22 CAR T cell therapy in childhood B cell acute lymphoblastic leukemia” by Dr. X. Wan, et al. Presented at the 2024 ASH Annual Meeting.
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