Abstract CT078: Impact of disease burden and transplant on long-term survival after CD19 CAR therapy in adults with relapsed B-cell acute lymphoblastic leukemia

Abstract

Abstract Objectives: CD19-specific chimeric antigen receptor (CAR) T cells have demonstrated high initial responses in patients with relapsed B-cell acute lymphoblastic leukemia (B-ALL). However, clinical characteristics associated with the durability of response remain undefined. Herein, we report the results from analysis of our phase I clinical trial of 19-28z CAR T cells in adult patients with relapsed B-ALL with a focus on impact of pre-treatment disease burden and post-CAR T cell allogeneic transplant on long-term clinical outcome. Methods: Adults with relapsed B-ALL were infused with autologous T cells expressing the 19-28z CAR. Disease burden was assessed by bone marrow biopsy immediately prior to T cell infusion. We grouped patients into 2 cohorts based on disease burden upon T cell infusion: minimal residual disease (MRD) with <5% blasts in bone marrow and morphologic disease (≥5% blasts). Median follow-up duration was 18 months (range, 0.2-57.3). Results: 51 adults received 19-28z CAR T cells; 20 in the MRD and 31 in the morphologic cohort. Complete remission (CR) rates were comparable (95% and 77%, respectively). However, median event-free and overall survivals widely diverged among the 42 patients who achieved MRD-negative CR: not reached (NR) (95% confidence interval [CI]: 4.2-NR) vs. 6.3 months (95% CI, 4.8-9.0) (p=0.0005), and NR (95% CI, 15.3-NR) vs. 17 months (95% CI, 8.5 - 36.2) (p=0.0189), in the MRD and morphologic cohorts, respectively. Subsequent allogeneic HSCT in either cohort did not improve survival (p=0.8). MRD cohort patients developed substantially less severe cytokine release syndrome (CRS) and neurotoxicity, both correlating with peak CAR T cell expansion (p=0.0326 and p=0.0001, respectively). Conclusion: Despite comparable initial CR rates between the two cohorts, durability of 19-28z CAR T cell mediated remissions and survival in adult patients with relapsed B-ALL positively correlated to a low disease burden and do not appear to be enhanced by allogeneic transplant. Our findings strongly support the early incorporation of CD19 CAR therapy before morphologic relapse in B-ALL. Citation Format: Jae H. Park, Isabelle Rivere, Xiuyan Wang, Brigitte Senechal, Kevin Curran, Craig Sauter, Yongzeng Wang, Bianca Santomasso, Daniel Li, Renier Brentjens, Michel Sadelain. Impact of disease burden and transplant on long-term survival after CD19 CAR therapy in adults with relapsed B-cell acute lymphoblastic leukemia [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr CT078. doi:10.1158/1538-7445.AM2017-CT078