Tisagenlecleucel Chimeric Antigen Receptor (CAR) T-Cell Therapy for Relapsed/Refractory Children and Young Adults with Acute Lymphoblastic Leukemia (ALL): Real World Experience from the Center for International Blood and Marrow Transplant Research (CIBMTR) and Cellular Therapy (CT) Registry

• Published in: Blood 2019-11, Vol.134 (Supplement_1), p.2619-2619
• Main Authors: Grupp, Stephan, Hu, Zhen-Huan, Zhang, Yiyun, Keating, Amy, Pulsipher, Michael A., Philips, Christine, Margossian, Steven P., Rosenthal, Joseph, Salzberg, Dana, Schiff, Deborah E., Yanik, Gregory, Curran, Kevin J., Harris, Andrew C., Hematti, Peiman, Nikiforow, Sarah, Steinert, Patricia, Yi, Lan, Chawla, Raghav, Horowitz, Mary M., Bleickardt, Eric, Pasquini, Marcelo C.
• Format: Article
• Language: English
• ISSN: 0006-4971; 1528-0020
• DOI: 10.1182/blood-2019-129279

Background Tisagenlecleucel is a CD19-directed genetically modified autologous T-cell immunotherapy approved for the treatment of patients up to 25 years of age with B-cell ALL that is refractory or in second or later relapse. In the pivotal ELIANA trial, 79 patients were treated with tisagenlecleucel. The best overall response rate (CR/CRi) was 82%; 98% of patients who achieved CR/CRi were also negative for minimal residual disease (MRD). With a median follow-up of 24 months, the median duration of remission was not reached. Grade 3 or higher cytokine release syndrome (CRS) by UPenn criteria and neurotoxicity within the first 8 weeks after infusion occurred in 49% and 13%, respectively (Grupp, et al. Blood 2018, Abstr 895). The CIBMTR CT Registry was developed to collect long-term safety and efficacy information on recipients of cellular immunotherapies and it is utilized for a post marketing study of tisagenlecleucel in the real world setting. Methods Clinical data from the CT registry were analyzed for baseline information. Efficacy and safety data were presented among patients with a minimum of 3 months follow-up. CRS and immune effector cell-associated neurotoxicity syndrome (ICANS) were reported as per the ASTCT consensus criteria. Additionally, manufacturing product characteristics of tisagenlecleucel were compared to clinical outcomes. The association of number of cells administered, cell viability, potency, and transduction efficiency of tisagenlecleucel to overall response, CRS and ICANS grades was performed using descriptive summaries and univariate logistic regression analyses. Results Forty centers in the U.S. contributed data for refractory or relapsed pediatric or young adult patients with B-cell ALL through the CIBMTR CT registry as of May 31, 2019. Baseline information was available for 159 patients; 105 patients had at least the first follow up assessment reported at 3 months (Table 1). The median follow-up of survivors was 5.8 months (2.6-16.9 months). All patients received cells in the approved range for their weight with a median of 1.9 x 106/kg (range 0.2-4.6 x 106/kg) for children ≤ 50 kg and 0.9 x 108 (range 0.1-2.3 x 108) for children and young adults > 50 kg. The best overall response rate (CR) was 88% (95% CI 80%-94%). MRD was collected in 52 patients after tisagenlecleucel; all were negative. Importantly, among the 4 patients age < 3 years of age with more than 3 months of follow-up, all attained a CR. The 6-month duration of re