Bicistronic CD19/CD22 CAR T-Cell Therapy Shows Durable Responses in Pediatric B-ALL
核心洞察
Bicistronic CD19 (搜索)/CD22 (搜索)-directed CAR T-cell therapy (B019) demonstrates safety and high remission rates in children with relapsed/refractory B-cell acute lymphoblastic leukemia (搜索) (B-ALL (搜索)).
The 1-year event-free survival (EFS) rate was 75.5%, and the 1-year overall survival (OS) rate was 93.5% among patients treated with the therapy.
Patients undergoing bridging bone marrow transplant after CAR T-cell expansion showed improved 1-year EFS rates compared to those without transplant (89.7% vs 76.8%).
Treatment with bicistronic CD19 (搜索)/CD22 (搜索)-directed CAR T-cell therapy (B019) has shown promising results in children with relapsed/refractory B-cell acute lymphoblastic leukemia (搜索) (B-ALL (搜索)), according to data from a phase 2 trial presented at the 2024 ASH Annual Meeting. The therapy demonstrated a high remission rate and durable responses, offering a potential new treatment option for this challenging patient population.
Efficacy and Survival Rates
The study, which included 343 pediatric patients, reported a 1-year event-free survival (EFS) rate of 75.5% and a 1-year overall survival (OS) rate of 93.5%. Notably, patients who underwent bridging bone marrow transplant following CAR T-cell expansion had improved 1-year EFS rates (89.7%) compared to those who did not (76.8%). However, the 1-year OS rates were similar between the two groups (95.8% vs 95.2%).
Hua Zhang, MD, PhD, vice president and chief scientific officer at SPH Biotherapeutics (搜索) (HK), Limited, noted that "After CAR T-cell therapy, we have found that the 1-year EFS [rate] is higher [with] CAR T-cell treatment plus bone marrow transplant than CAR T-cell treatment alone, [although the] 1-year OS [rates were] very similar between these 2 [populations]."
Cytokine Release Syndrome (CRS)
While most patients experienced cytokine release syndrome (CRS), the severity of CRS was correlated with EFS outcomes. Patients with lower-grade CRS (grade 1/2) had a 1-year EFS rate of 80.9%, while those with higher-grade CRS (grade 3/4) had a 1-year EFS rate of 69.9% (P = .0191). Zhang also noted that the severity of CRS was highly correlated with disease burden and CAR T-cell viability, but not with the study dose range of infused cells.
Trial Design and Patient Characteristics
The phase 2 trial enrolled patients aged 0 to 18 years with relapsed/refractory B-ALL (搜索). Following enrollment, patients underwent debulking and lymphodepletion before receiving the CAR T-cell infusion at a dose of 1 x 106/kg to 10 x 106/kg. The study included patients with isolated extramedullary disease (n = 51) and those with refractory/isolated/combined hematologic relapse (n = 292).
Complete Remission Rates
Complete remissions (CRs) were 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 prior to evaluation.
Future Directions
Based on these promising results, a phase 1 study of the bicistronic CD19 (搜索)/CD22 (搜索) CAR T-cell therapy is currently underway. Investigators plan to enroll 12 to 18 patients to further evaluate the safety and efficacy of this novel treatment approach.