Key Points

  • We present results of a clinical trial that show the safety of CD19-specific CAR T cell therapy for R/R B-ALL.

  • Conditioning chemotherapy dose intensity and minimal pre-treatment disease burden positively impact response without an increase in toxicity

Chimeric antigen receptor (CAR) T cells have demonstrated clinical benefit in patients with relapsed/refractory (R/R) B-cell acute lymphoblastic leukemia (B-ALL). We undertook a multi-center clinical trial to determine toxicity, feasibility, and response for this therapy. A total of 25 pediatric/young adult patients (age 1-22.5 years) with R/R B-ALL were treated with 19-28z CAR T cells. Conditioning chemotherapy included high dose (3 g/m2) cyclophosphamide (HD-Cy) for seventeen (n=17) patients and low dose ({less than or equal to}1.5 g/m2) cyclophosphamide (LD-Cy) for eight (n=8) patients. Fifteen (n=15) patients had pre-treatment minimal residual disease (MRD; <5% blasts in bone marrow) and ten (n=10) patients had pre-treatment morphologic evidence of disease ({greater than or equal to}5% blasts in bone marrow). All toxicities were reversible including severe CRS in 16% (4/25) and severe neurotoxicity in 28% (7/25) of patients. Treated patients were assessed for response and among evaluable patients (n=24), response and peak CAR T cell expansion were superior in the HD-Cy/MRD cohorts as compared to the LD-Cy/morphologic cohorts without an increase of toxicity. Our data supports the safety of CD19-specific CAR T cell therapy for R/R B-ALL. Our data also suggest that dose intensity of conditioning chemotherapy and minimal pre-treatment disease burden have a positive impact on response without a negative effect on toxicity. This trial was registered at as NCT01860937.

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