IL-6 and ferritin levels predict the severity of cytopenia post CAR T-cell treatment with axi-cel for B cell lymphoma

Abstract Background: Chimeric Antigen Receptor (CAR) T-cell therapy is a promising treatment for hematologic malignancies such as B cell lymphomas but is associated with toxicities. Immune effector cell-associated hematotoxicity syndrome (ICAHT) which is serious but incompletely understood complication of CAR T-cell therapy. Understanding the incidence and risk factors for these adverse events remains essential for optimizing patient outcomes. Methods: A retrospective analysis of 85 patients with B cell lymphoma underwent Axi-cel CAR T-cell therapy was conducted. Patient demographics, overall survival (OS), incidence of ICANS, CRS, and cytopenias were evaluated. Risk factors for grade ≥3 cytopenias and prolonged cytopenias (>30 days) were assessed using univariate and multivariate logistic regression analyses. Results: The cohort included male 53 (63%) and female 32 (37.6%) patients with a median age of 53 (IQR:36 – 52) years. The 12-month OS was 75%. CRS was observed in 90.7% of patients, Grade 1 (28.2%), Grade 2 (35.9%), Grade 3 (23.1%), and Grade 4 (12.8%). Immune effector cell-associated neurotoxicity syndrome (ICANS) occurred in 83.7% of cases (Grade 1: 34.7%, Grade 2: 30.6%, Grade 3: 22.2%, Grade 4: 12.5%). Thrombocytopenia was reported in 62.8% of patients at different grades (Grade 1: 22.2%, Grade 2: 27.8%, Grade 3: 25.9%, Grade 4: 24.1%), while neutropenia was seen in 54.7% (Grade 1: 8.5%, Grade 2: 19.1%, Grade 3: 25.5%, Grade 4: 46.8%). Thrombocytopenia persisted for ≥30 days in 55.3% of cases and <30 days in 44.7%. Neutropenia lasted ≥30 days in 52.9% and <30 days in 47.1%. Anemia persists for ≥30 days was seen in 58.8% and <30 days in 41.2% of patients. Risk factors for grade 3-4 thrombocytopenia included pre Axi-cel infusion IL-6 >12 pg/mL (3-fold risk, P=0.026), ferritin >400 ng/mL (9-fold risk, P<0.001), time from last chemotherapy to lymphodepletion <45 days (5-fold risk, P=0.009), bone marrow involvement (2-fold risk, P=0.05), and pre-lymphodepletion thrombocytopenia (14-fold risk, P<0.001). Bridging radiation therapy was protective against neutropenia (0.4-fold risk, P=0.03). Prolonged cytopenias were associated with pre Axi-cel infusion IL-6 >12 pg/mL (4-fold risk for anemia, P=0.003), ferritin >400 ng/mL (2.5-fold risk for anemia, P=0.037; 4-fold risk for thrombocytopenia, P=0.008), time from last chemotherapy to lymphodepletion <45 days (P=0.04), and high LDH >400 (P=0.01 for anemia). In multivariate analysis, IL-6 was the only significant factor for anemia (OR=2.95, 95% CI 1.1-7.8, P=0.02), and ferritin was the only significant factor for prolonged thrombocytopenia (OR=3.5, 95% CI 1.3-9.8, P=0.01). For severe thrombocytopenia, significant factors included ferritin (OR=8.5, 95% CI 1.9-37.5, P=0.004), time from last chemotherapy to lymphodepletion <45 days (OR=0.23, 95% CI 0.06-0.9, P=0.03), and pre-lymphodepletion thrombocytopenia (OR=0.1, 95% CI 0.01-0.5, P=0.006). Conclusion: CAR T-cell therapy is associated with significant cytopenias, with IL-6 and ferritin levels as key predictors of anemia and thrombocytopenia, respectively. Pre-treatment factors such as recent chemotherapy and bone marrow involvement further increase the risk of cytopenias. These findings highlight the need for tailored monitoring and management strategies to mitigate hematologic toxicities in CAR T-cell therapy patients.