Single Center Real Life Experiences in the Treatment of Pediatric, Adolescent and Young Adult ALL Patients Using Commercially Available CAR-T-Cells in Germany - Susceptibility to Bridging Chemotherapy Predicts Response.

Background Although children, adolescents and young adult patients with ALL have in general a good prognosis relapses occur and patients with a second relapse, a relapse after allogeneic SCT or patients with primary refractory disease have a poor prognosis. In this patient group several studies using second generation CD19 chimeric antigen receptor T- cells (CAR-T cells) demonstrated high efficacy with survival rates of up to 65%. Here we report our first results using commercially available CAR-T-cell product Tisagenlecleucel in patients with ALL. Methods, Patients Between May 2016 and August 2019 twenty-six patients received a peripheral blood apheresis for CAR-T cell generation. Twenty-four patients had relapsed after allogeneic HSCT (92%), one patient suffered from second r/relapse (4%) or from primary r/ALL (4%). In 23/26 (88%) patients CAR-T cell production was possible after first apheresis, in 2 patients (4%) a second apheresis was necessary after failure of the first transduction. Patients\u0027 median age was 13.5 years (range: 1.1-33.2 years). Between apheresis and start of lymphodepleting chemotherapy (LDC) 24 patients received low dose maintenance chemotherapy according to the FRAPOSTALL protocol (Willasch et al. 2016) and two patients were treated with inotuzumab. Disease status at start of LDC was CR w/o MRD (n=12), and persistence of blasts (n=11). Results CAR-T cells could be transfused to 23/26 patients at a median dose of 1.5 Mio/kgBW (range 0.145 to 8.5) /kgBW. In two patients (8%) CAR-T cell production was not possible and in one patient, in whom a second viral transduction procedure was necessary, CAR-T cell transfusion could not be performed because of diseases progression and deterioration of the patients\u0027 general condition. Cytokine release syndrome (CRS) grade I-IV was observed in seven patients (30%); 14/23 patients (70%) did not develop CRS. Cytokine related encephalopathy syndrome (CRES) grade II was observed in 4/23 patients (17%). At day +28 17/23 patients (74%) achieved MRD negative CR. Three patients (13%) did not respond and three patients died before day +28. Thereof two patients (8%) with progressive disease at time of LDC who did not respond, and unfortunately one patient (4%) died in CR based on infection before day +28. As of 8/20/2019 median follow-up was 9.5 months. Patients with Conclusion These results confirm that commercial available CAR-T cell product Tisagenlecleucel (Kymriah®) showed high efficacy in ALL patients. Response to bridging chemotherapy and level of residual diseases prior to CAR-T infusion might impact the pEFS and survival of the patients.