2.1 CASE 1
A 34-year-old male with refractory T-cell rich DLBCL with associated HLH/MAS at diagnosis, underwent Tisa-Cel therapy in 2019. High tumor burden with progressive disease was documented after bridging therapy.
During lymphodepletion with cyclophosphamide and fludarabine, persistent fever with neutropenia was treated with empiric broad-spectrum antimicrobials agents, without resolution.
On day +1, he presented with grade 1 CRS, managed with tocilizumab on days +15 and +20, achieving partial response. However, high grade fever followed with hyperferritinemia (peak 50,000ng/ml on day +23), severe cytopenias, altered liver function, coagulopathy and high values of IL-15, IL-1β, GM-CSF and IL-6. HLH/MAS was suspected and bone marrow aspiration was performed on day +22, showing hemophagocytosis and no evidence of infiltration by lymphoma.
In order to distinguish between CAR-T cell related and malignancy associated HLH/MAS, a PET-CT was performed on day +25, showing paradoxical response. Concurrently, CAR-T cells expansion in peripheral blood (PB) was detected by flow cytometry and polymerase chain reaction (PCR). Furthermore, a lymph node biopsy was performed where CAR-T cells were detected, with only 4% of neoplastic lymphocytes (Figure 1).
Subsequently, high dose corticosteroids, siltuximab, anakinra and cyclophosphamide were administered. Hemoadsorption with extracorporeal cytokine adsorber (CytoSorb®) was initiated on day +35. Etoposide was not considered due to severe liver function impairment.
Patient showed no response to treatment, and died from multiorgan failure on day +36. Tumor necrosis was the predominant finding in necropsy, with an estimated 15% of residual tumor.