19-28z CAR T Cells Induce Complete Response in Acute B Lymphoplastic Leukemia
CHICAGO—CD-19 targeted 19-28z chimeric antigen receptor (CAR)-modified T cells induced a high complete response rate in patients with relapsed or refractory acute B lymphoplastic leukemia (B-ALL), long-term outcome data from a phase 1 study presented at the 2015 American Society of Clinical Oncology (ASCO) Annual Meeting has shown.
These findings “strongly support” use of 19-28z CAR T cells in this population, which has a “dismal prognosis,” and warrants a phase 2 trial, said Jae Hong Park, MD, a medical oncologist at Memorial Sloan Kettering Cancer Center in New York, NY.
In the phase 1 trial, “patients with relapsed or refractory CD19+ B-ALL underwent leukapheresis, and T cells were transduced with a gamma retroviral vector encoding a CAR construct composed of anti-CD19 scFv linked to CD28 and CD3ζ signaling domains (19-28z),” he reported. Relapse after allogenic hematopoietic stem cell transplantation (HSCT) was allowed.
All patients received conditioning chemotherapy followed by 1–3x106 19-28z CAR T cells/kg.
Patients with active CNS disease, active graft-versus-host disease requiring immunosuppressants, or significant heart disease were excluded from the study.
Of the 39 patients treated, 38 were evaluable for response assessment with 1 month or longer follow-up. Median age was 45 years (range: 22-74 years) and 76% were male. A total of 13 patients (33%) had Philadelphia chromosome (Ph)+ T315I mutation; 14 (36%) had prior allogeneic stem cell transplant (allo-SCT); and 20 (51%) had 3 or more prior lines of therapy.
At the time of CAR T cell infusion, 20 had morphologic disease (>5% blasts in bone marrow) and 18 had minimal residual disease (MRD). After 19-28z CAR T cell infusion, 16 of the 20 patients with morphologic disease (80%) and 17 of the 18 patients with minimal residual disease (94%) were in complete remission (CR), for an overall CR rate of 87% (33 of 38 patients).
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Of the 32 patients evaluable with minimal residual disease, the minimal residual disease-negative CR rate was 81%. Median time to CR was 23.0 days (range: 8-46 days). Thirteen patients underwent allo-SCT following CAR T cell infusion.
As of the March 30, 2015, median follow-up was 5.6 months (range: 1.0-38+ months) and median duration of response or relapse-free survival was 5.3 months (95% CI: 3,9).
Dr. Park said depth of response, as denoted by MRD negativity, is correlated with overall survival (OS). The 6-month OS rate for all patients was 59% (95% CI: 39,74); median OS was 8.5 months. Among MRD patients, median OS was 10.8 months; OS rate was 75% (95% CI: 50,89).
Among those who had allo-SCT following CAT T cell infusion, median OS was 9.9 months compared with 8.5 months for those who did not undergo allo-SCT (P=0.5). Severe cytokine release syndrome, which correlates with disease burden and required vasopressors or mechanical ventilation for hypoxia, was observed in 9 patients and was effectively managed with IL-6R inhibitor and/or corticosteroids.
- Park JH, Riviere I, Wang X, et al. Efficacy and safety of CD19-targeted 19-28z CAR modified T cells in adult patients with relapsed or refractory B-ALL. J Clin Oncol. 2015;33:(suppl; abstr 7010).