Real-Life CAR-T Cell Treatment in Large B-Cell Lymphomas Indicates That Axi-Cel and Tisa-Cel Have Similar Outcomes, but Long-Term Cytopenia Is an Emerging Problem

Introduction. The outcome of relapsed/refractory large B-cell lymphomas, not eligible or cured by high dose chemotherapy due to persistent disease, is very unsatisfactory. The introduction of anti-CD19 chimeric antigen receptor T cells (CAR-T) in this setting, showed impressive long-term results in registrative trials. Axicabtagene ciloleucel (axi-cel) and tisagenlecleucel (tisa-cel) are registered and reimbursed in Italy by Agenzia Italiana del Farmaco (AIFA) for the treatment of relapsed/refractory (R/R) diffuse large B-cell lymphoma (DLBCL) and primary mediastinal B-cell lymphoma (PMBCL) patients after at least 2 lines, with an ECOG 0-1, and an age lower than 71 years. To evaluate in real-life the patients treated in Italy with CAR-T cells, the Italian Society of Hematology (SIE) designed an observational study. Methods. The CART-SIE is an ongoing prospective and retrospective observational trial with the following aims: 1. consecutively register all DLBCL and PMBCL treated in the Italian authorized centers; 2. evaluate the intention to treat overall response rate (ORR, complete [CR] and partial response [PR]), duration of response (DOR), progression free survival (PFS) and overall survival (OS); 3. evaluate safety in terms of cytokine release syndrome (CRS), immune effector cell-associated neurotoxicity syndrome (ICANS) and long-term cytopenia; 4. compare the two different CAR-T products. Primary endpoint was to evaluate the overall response and survival at one year of the patients receiving CAR-T cells. Results. Since March 2019 to June 2021, 208 patients were enrolled and leukapheresed; 191 patients were infused (92%); 17 were not due to rapidly progressive disease and worsening of clinical conditions (11), severe infection (4), persistent complete remission (1) and manufacturing failure (1). Clinical characteristics of the 191 infused patients were: median age 53 years (range 19-70), stage III/IV 127 (69%); median number of prior lines was 3 (2-12), including 58 (30%) with prior autologous stem cell transplantation. According to local pathology reports, 134 (70%) were DLBCL, 22 (12%) high-grade B-cell lymphoma (HGBCL) and 35 (18%) PMBCL. Bridging therapy was delivered to 177 (93%) patients: 45 (25%) radiotherapy, 115 (65%) systemic therapy (chemotherapy and/or immunotherapy), 17 (10%) combined therapy (radiotherapy + chemotherapy). All patients received Fludarabine-Cyclophosphamide as lymphodepletion regimen. Axi-cel was infused in 92 (48%), and tis