Abstract CT102: Efficacy and toxicity management of 19-28z CAR T cell therapy in B cell acute lymphoblastic leukemia

Abstract

Abstract Chimeric antigen receptors (CARs) are artificial receptors for antigen that redirect antigen specificity, activate T cells and further enhance T cell function through their costimulatory component. Three groups, including our own, have reported objective tumor responses when infusing autologous T cells genetically modified with CD19-targeted CARs into patients with chronic lymphocytic leukemia (CLL), other indolent non-Hodgkin lymphomas (NHL) and, most dramatically in patients with relapsed or refractory B cell acute lymphoblastic leukemia (B-ALL). Here we report on 16 patients with relapsed or refractory B-ALL that we treated with autologous T cells expressing the 19-28z CAR specific to the CD19 antigen. The overall complete response rate was 88%, as assessed by morphological criteria and IgH deep sequencing. This allowed us to transition a majority of these patients to a standard of care allogeneic hematopoietic stem cell transplant (allo-SCT). This therapy was as effective in high-risk patients with Ph+ disease as in those with relapsed disease following prior allo-SCT. Through systematic analysis of clinical data and serum cytokine levels over the first 21 days following T cell infusion, we have defined diagnostic criteria for a severe cytokine release syndrome (sCRS), with the goal of better identifying the subset of patients who will likely require therapeutic intervention with corticosteroids or interleukin-6 receptor blockade to curb the CRS. Additionally, we found that serum C-reactive protein (CRP), a readily available laboratory study, can serve as a reliable indicator for the severity of the CRS and a road map for patient management at centers now contemplating the use of CAR T cell therapy. Based on these remarkably robust clinical results and the toxicity management algorithm we present here, we will soon open a multi-center Phase II clinical trial to further evaluate the efficacy of 19-28z CAR T cells and prospectively validate our proposed CRS monitoring and intervention guidelines in patients who are treated with CAR therapy. Citation Format: Michel Sadelain, Renier Brentjens, Marco Davila, Isabelle Riviere, Xiuyan Wang, Shirley Bartido, Jae Park, Diana Bouhassira, Kevin Curran, Stephen Chung, Jolanta Stefanski, Oriana Borquez-Ojeda, Sergio Giralt. Efficacy and toxicity management of 19-28z CAR T cell therapy in B cell acute lymphoblastic leukemia. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr CT102. doi:10.1158/1538-7445.AM2014-CT102