IMMUNE EFFECTOR CELL-ASSOCIATED HLH IN HIGH TUMOR BURDEN PATIENTS TREATED WITH CAR-T: LESSONS FROM BRAZILIAN CASES

CAR-T cell therapy is based on the modification of T lymphocytes to express chimeric receptors. Although effective in the treatment of B-cell malignancies, these therapies are associated with inflammatory toxicities such as Cytokine Release Syndrome (CRS), Immune Effector Cell-Associated Neurotoxicity Syndrome (ICANS), and, more rarely, Immune Effector Cell-Associated Hemophagocytic Lymphohistiocytosis (IEC-HLH). We report two cases of IEC-HLH in patients who received anti-CD19 CAR-T infusion as part of a Brazilian academic study. Case 1: Male, 70 years old, with refractory CLL (TP53 mutated, 11 prior lines, including allo-HSCT). Pre-CAR-T bone marrow showed 83% clonal lymphocytes. Developed grade I CRS on D+1, treated with tocilizumab 8 mg/kg. On D+15, presented with fever, cytopenias, hyperferritinemia (7,417 ng/mL), hypofibrinogenemia, hypertriglyceridemia, elevated transaminases and LDH, with an H-Score of 200. Treated with a cumulative dose of 329 mg dexamethasone and anakinra (10–5 mg/kg/day) for 7 days, achieving complete resolution. Case 2: Male, 9 years old, with ALL and bone marrow showing 95% blasts, received prophylactic tocilizumab. Developed grade III CRS (D+1) and grade IV ICANS (D+5), both treated with immunosuppressants. On D+6, presented with findings suggestive of IEC-HLH: ferritin 43,044 ng/mL, cytopenias, hypofibrinogenemia, elevated transaminases, and triglycerides, with an H-Score of 184. Received anakinra (10–7 mg/kg/day for 7 days) with complete clinical and laboratory response. On D+30 bone marrow reassessment, he achieved MRD-negative complete remission, maintained to date (D+367). Both patients had high tumor burden and developed IEC-HLH later than CRS onset. The CLL patient showed late CAR-T cell expansion (0.45% to 38.1% between D+14 and D+21) coinciding with a decline in CD19+ cells (82.2% to 1.2%), suggesting a correlation between cell expansion and IEC-HLH. Both cases were treated with anakinra, in line with prior experience in secondary HLH. Therapeutic response was satisfactory. Both patients remain in complete remission (>1 year post-infusion). These cases highlight the importance of recognizing IEC-HLH in patients with high tumor burden. The favorable outcomes with anakinra suggest its potential as a standardized therapeutic strategy. Specific protocols are essential for the diagnosis and management of this rare but potentially severe complication.