SAN DIEGO — A fourth generation, safety-improved CD19–specific chimeric antigen receptor T-cell treatment option demonstrated safe and effective results in patients with late-stage, chemotherapy resistant and very high-burden acute B-cell lymphoblastic leukemia, according to findings from a phase 1/phase 2 multi-center trial presented at the ASH Annual Meeting and Exposition.
Lung-Ji Chang, PhD, from the department of molecular genetics and microbiology at the University of Florida, and colleagues conducted a multi-center trial of 102 eligible children and adults from 22 clinical sites with B-ALL to assess the safety and efficacy of a fourth-generation CAR T cell.
Fifty-five children (median age, 9 years) and 47 adults (median age, 37 years) were included in the study.
Twenty-seven patients received allogeneic hematopoietic stem cell transplantation prior to CAR T-cell infusion. Median leukemia blast count in the bone marrow was 14.5%, with bone marrow blasts of 50% or greater occurring in nearly one-third of patients (n = 33).
Patients received conditioning regimens of cyclophosphamide (n = 17), cyclophosphamide/fludarabine (n = 54), other chemotherapy (n = 29) or none (n = 2), followed by CAR-T cell infusion (average 1.05x106 cells/kg).
Median follow-up time during the study was 7 months.
Patients with a bone marrow blast count of less than 50% (n = 69) achieved a 91.3% complete response rate, and patients with a bone marrow blast count of 50% or more (n = 33) achieved a 75.8% complete response rate.
Patients with the lower bone marrow blast count reached a median OS of 485 days and patients from the higher bone marrow blast count reached a median OS of 317 days.
The infusion dose of CAR T cells positively correlated with OS in pediatric patients (P = .041), however it lacked significant correlation in adults (P = .95).
“[This suggests] that other factors, rather than CAR T infusion dose, play an important role in CAR T therapy in adults,” Chang said during the presentation.
Seventy-three patients experienced a grade 1 or less episode of cytokine release syndrome – eight of whom had a bone marrow leukemia load count greater than 80%.
Of the 17 patients with bone marrow blast counts greater than 80%, only three experienced grade 3 or grade 4 CRS.
“The three-year follow-up of the 4SCAR19 T-cell therapy further supports that CAR T immunotherapy could benefit not only low leukemia burden patients, but also late-stage, chemo-resistant [ and] very high-burden leukemia patients,” Chang said. “Importantly, our study demonstrates a good safety profile of the 4SCAR19 T cells, even under high disease burden. While the multi-center trial involves 22 clinical centers, the variable clinical settings do not seem to impact patient outcomes due to the highly-standardized CAR T-cell preparation protocol and manageable CRS in most.” – by Ryan McDonald
For more information:
Chang LJ, et al. Abstract 587. Presented at: ASH Annual Meeting and Exposition; Dec. 3-6, 2016; San Diego.
Disclosure: The researchers report no relevant financial disclosures.