Pb2314: cytopenias and blood transfusion support after car-t therapy

Topic: 19. Aggressive Non-Hodgkin lymphoma - Clinical Background: Chimeric antigen receptor T-cell (CAR-T) therapy has improved outcomes in relapsed/refractory patients with haematological malignancies. Hematotoxicity, including neutropenia, anaemia, and thrombocytopenia, is frequent after CAR-T therapy. Aims: To assess risk factors, incidence and evolution of cytopenias following CAR-T therapy. Methods: A retrospective, single institution analysis was conducted on adult patients who received commercial CAR-T [tisa-cel or axi-cel] for large B-cell lymphoma between December 2019 and December 2022. Cytopenias were graded according to CTCAE v5.0 and its grade as well as blood transfusion and granulocyte colony-stimulating factor [G-CSF] dependence was assessed at different intervals during follow-up [30, 60, 90, 180 and 365 days]. Blood transfusion or G-CSF dependence was defined as requiring any transfusion or G-CSF support within one week before evaluation to maintain haemoglobin, platelet and neutrophil count above 8 g/dL, 20000/L and 500/mcL, respectively. Patients who died or progressed were excluded from the analysis. Univariate logistic regression was used to estimate the association between baseline factors and transfusion or G-CSF dependence. Cytokine-release syndrome [CRS] and immune-effector cells associated neurotoxicity [ICANS] were graded following ASCTC criteria. Results: Forty-eight patients were included in the study. An overall response ratio [ORR] was achieved in 29 [60%] patients [complete response, n= 22; partial response, n= 7] at a median time of 35 days [29 – 187]. ORR was maintained in 14 patients at last follow-up. Nine-teen [40%] patients remained alive at a median follow-up of 375 days [60 - 1031]. Nine [18%] patients died of toxicity [infection, n=6; CRS, n=1; ICANS, n=1; undetermined, n=1] at a median time of 52 days [6 – 830]. The grade of cytopenias at different time points is depicted in Figure 1. Of the 48 patients, 43 [67%] and 22 [44%] patients developed grade 4 neutropenia or ≥3 thrombocytopenia at a median time of 2 days [-50 – 24] and 7 days [-119 – 32] after CAR-T infusion, respectively. Thirty-two [67%] patients required blood transfusion support during follow-up with a median of 2 (range 0 to 49) blood transfusions and 2 (range 0 to 87) platelet transfusions. The percentage of transfused patients progressively decreased over time, with 66%, 21% and 25% of patients requiring transfusions within days 0-90, 90-180 and beyond 180, respectively. Twenty [43%], 20 [43%] and 12 [26%] of the 46 evaluable patients at day 30 were considered blood transfusion, platelet transfusion and G-CSF independent, respectively. A multivariate analysis was carried out to identify factors related to transfusion or G-CSF dependence: blood transfusion dependence was associated with ICANS [OR 8.97, 95% CI, 1.64 – 49, p = 0,011] and disease stage IV [OR 15.7, 95% CI, 2.03 – 121, p = 0,008]; platelet transfusion requirement was associated with ICANS [OR 14.2, 95% CI, 1.77 – 115, p = 0.013] and HTC-CI≥1 [OR 26.4, 95% CI, 1.68 – 415, p = 0.02]; and G-CSF dependence was associated with EASIX socre above 3.645 [OR 5.31, 95% CI, 1.37 – 20.6, p = 0.016]. Summary/Conclusion: Cytopenias are a frequent complication following CAR-T therapy. Patients usually require G-CSF support and/or irradiated blood components (especially during the first two months), which can stress blood bank reserves. Prelymphodepletion EASIX score and ICANS are risk factors for transfusion or G-CSF dependence one month after CAR-T infusion, meaning that endothelial activation and immune disruption may have a negative impact on blood counts following CAR-T therapy.Keywords: CAR-T, Hematotoxicity, Diffuse large cell lymphoma