Anti-human CD117 CAR T-cells efficiently eliminate hematopoietic stem and CD117-positive AML cells

Abstract

Background: EBV þ LMS is a rare cancer that develops in patients with immune deficiency. EBV þ LMS responds poorly to radiation and chemotherapy resulting in limited treatment options and poor outcomes.1 Tabelecleucel is an investigational, off-theshelf, genetically unmodified, allogeneic T-cell immunotherapy targeting EBV antigens.Here we report the efficacy and safety of tabelecleucel in a subgroup of EBV þ LMS patients from 3 clinical trials. Methods: Tabelecleucel was evaluated in 2 single-center, open-label studies (NCT00002663 [Study 1], NCT01498484 [Study 2]) and a multi-center expanded access protocol (NCT02822495 [Study 3]). Tabelecleucel was given at 1.0-2.0 x 10 6 cells/kg/dose on days 1, 8, and 15 of every 4-6-week cycle, and imaging was performed before the 1 st dose of each cycle. Results: A total of 12 patients with EBV þ LMS received 1 dose of tabelecleucel, 10 of whom were assessed for responses (1 patient was not evaluable and 1 patient was too early to assess). Using CT-based RECIST 1.1 criteria, 2 patients achieved a partial response (objective response rate ¼ 17%) and 8 patients achieved stable disease. In studies 1 and 2 where longer follow-up is available, 6 of 8 patients survived 27 months. The median survival (95% CI) is 77.4 (18, NE) months. At the time of this analysis, metabolic responses were available in study 3: 3 of the 4 patients (75%) achieved a metabolic response. The safety profile is consistent with previously reported data; 2 no new safety signals have been identified. Conclusions: This analysis represents one of the larger prospective studies of patients with EBV þ LMS. The combination of CT-based and metabolic responses to tabelecleucel, in the context of prolonged survival, demonstrate that tabelecleucel (also known as tab-cel TM ) may provide clinical benefit in this typically radiation-and chemotherapyresistant disease. Tabelecleucel is well tolerated in this population of patients.