Marco L. Davila; Isabelle Rivière; Xiuyan Wang; Shirley Bartido; Jae H. Park; Kevin J. Curran; Stephen S. Chung; Jolanta Stefanski; Oriana Bórquez-Ojeda; Malgorzata Olszewska; Jinrong Qu; Teresa Wasielewska; Qing He; Mitsú J. Fink; Himaly Shinglot; Maher Youssif; Mark Satter; Yongzeng Wang; James Hosey; Hilda Quintanilla; Elizabeth Halton; Yvette Bernal; Diana Bouhassira; Maria E. Arcila; Mithat Gönen; Gail J. Roboz; P. Maslak; Dan Douer; Mark G. Frattini; Sergio Giralt; Michel Sadelain; Renier J. Brentjens · 2014 · Science Translational Medicine
Paper
We report on 16 patients with relapsed or refractory B cell acute lymphoblastic leukemia (B-ALL) that we treated with autologous T cells expressing the 19-28z chimeric antigen receptor (CAR) specific to the CD19 antigen. The overall complete response rate was 88%, which allowed us to transition most 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 Philadelphia chromosome-positive (Ph(+)) disease as in those with relapsed disease after previous allo-SCT. Through systematic analysis of clinical data and serum cytokine levels over the first 21 days after 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 sCRS. Additionally, we found that serum C-reactive protein, a readily available laboratory study, can serve as a reliable indicator for the severity of the CRS. Together, our data provide strong support for conducting a multicenter phase 2 study to further evaluate 19-28z CAR T cells in B-ALL and a road map for patient management at centers now contemplating the use of CAR T cell therapy.
Analysis
This study evaluates the efficacy and toxicity of 19-28z CAR T cell therapy in 16 patients with relapsed or refractory B cell acute lymphoblastic leukemia (B-ALL), demonstrating a high complete response rate and providing insights into managing severe cytokine release syndrome (sCRS).
Discovery
Hany E. Marei
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