Work

Late Hematotoxicity in Relapsed/Refractory (R/R) Large B Cell Lymphoma (LBCL) Patients Treated with CD19-Directed Chimeric Antigen Receptor T Cell: A Cell Therapy Consortium Analysis

Year: 2025

Type: article

Abstract: Introduction Chimeric antigen receptor (CAR) T cell therapy is known for its unique toxicities. In addition to the widely recognized cytokine release syndrome (CRS) and neurotoxicity (ICANS), hematologic toxicity has been increasingly reported. While cytopenia typically occurs in the early phase of treatment, it can be severe and persist for an extended period. This study explores the characteristics, and risk factors of late cytopenia , defined as cytopenia after 30 days post-CAR T cell therapy. Methods This retrospective multicenter study included patients with relapsed/refractory large B cell lymphoma (r/r LBCL) who received commercial CD19 CAR T cell therapy at 8 US medical centers affiliated with the Cell Therapy Consortium between 2018 and 2023. The study examined the occurrence and pattern of late cytopenia . Cytopenia was defined as cytopenia grade 3 or higher per the Common Terminology Criteria for Adverse Events . Risk factors for late cytopenia were analyzed. Results A total of 452 patients with r/r LBCL treated with CD19 CAR T cell (204 axi-cel, 153 tisa-cel, 95 liso-cel) were included. The median age at CAR T infusion was 65 years (interquartile range [IQR] 57-71 years). The most common indication for CAR T cell therapy was diffuse large B cell lymphoma (N=360; 80%). The median number of prior therapies before CAR T cell therapy was 3 (IQR 2-4), including hematopoietic cell transplant in 104 patients (23%). A total of 332 (73%) patients had advanced stage disease at the time of leukapheresis , and 288 (64%) received bridging therapy, including chemotherapy in 144 patients (32%). Of 326 patients for whom CAR HAEMATOTOX score at the time of infusion was calculable, 154 (47%) were in the high-score group. Fludarabine-Cyclophosphamide was the most common lymphodepletion regimen, used in 363 patients (80%). CRS and ICANS were observed in 272 (60%) and 146 patients (32%), respectively, including grade ≥3 in 25 (6%) and 81 (18%) patients. Figure 1 summarizes baseline characteristics of patients. After censoring patients who were lost to follow up or had competing events (relapse, initiation of anti-lymphoma therapy or death) at each time point, the proportion of patients who had late cytopenia was 129/446 (29%) at day 30, 57/380 (15%) at day 60, 42/349 (12%) at day 90, 26/268 (10%) at 6 months, 9/203 (4%) at 9 months, 8/165 (5%) at 1 year, and 3/95 (3%) at 2 years post-CAR T cell therapy. Figure 2 shows overall and lineage-specific cytopenia at each time point after CAR T infusion. Multivariable Cox regression analysis shows that a high CAR HAEMATOTOX score (>2) was associated with late cytopenia at 3 and 6 months after adjusting for product, bridging therapy, prior treatments, baseline CCI, and severe ICANS. Conclusion Late cytopenia is a common toxicity after CD19 CAR T cell therapy and can have a prolonged course. CAR HAEMATOTOX index is an independent predictor of late cytopenia after CD19 CAR T cell therapy.

Source: Transplantation and Cellular Therapy

DOI: 10.1016/j.jtct.2025.01.560