Hemofiltration Successfully Eliminates Severe Cytokine Release Syndrome Following CD19 CAR-T-Cell Therapy

Abstract

Cytokine release syndrome (CRS) remains to be a major adverse effect of chimeric antigen receptor T (CAR-T) cell therapy in B-cell acute lymphoblastic leukemia (B-ALL) and lymphoma. It was urgent to explore novel strategy for managing severe CRS. We conducted a clinical trial to assess the safety and efficacy of CD19-targeting CAR-T-cells in the treatment of relapsed and chemotherapy-refractory B-ALL and lymphoma. A 10-year-old boy with B-ALL who never achieved minimal residual disease (MRD) negative status after 5 courses of chemotherapy was enrolled into our study and received a total of 3.19×106/kg autologous CD19 CAR-T-cells. Before CAR-T-cell infusion, naive lymphocytes made up 41.8% of bone marrow cells, which were reduced to 1% at the 14th day after transfusion, with MRD<10−4. However, this patient developed grade 4 CRS, multiple organ failure, hemophagocytic syndrome, neurotoxicity, and severe pulmonary infection after CAR-T-cell therapy. Tocilizumab and glucocorticoids treatment were ineffective for controlling the adverse effects and in contrast, hemofiltration immediately ameliorated the severe CRS and prevented the exacerbation of multiple organ dysfunction, pneumonia, and hydrosarca caused by CAR-T-cell therapy. All side effects disappeared within days following hemofiltration. Hemofiltration helped quickly clear cytokines, speeded up patient recover, and successfully resolved the severe CRS crisis. This was the first report, reporting the successful use of hemofiltration to eliminate adverse reactions of CAR-T-cell therapy.

A comprehensive analysis of the fatal toxic effects associated with CD19 CAR-T cell therapy

“…We mainly use anti-IL-6 monoclonal antibodies to treat CRS, such as tocilizumab and siltuximab. Some studies have shown that therapeutic plasma exchange (TPE) may be the other option [ 13 ]. The use of glucocorticoids is also one of the main therapeutic methods, which are generally used to supplement anti-IL-6 therapy [ 14 , 15 ].…”

Point mutation inCD19facilitates immune escape of B cell lymphoma from CAR-T cell therapy

“…gov number, NCT03156101). 13 End points for this study included safety, overall survival, duration of response, and CD19 CAR-T cellular kinetics. These patients were subjected to lymphodepleting chemotherapy with fludarabine (25 mg/m 2 body surface area per day) for 3 days, and cyclophosphamide (500 mg/m 2 body surface area per day) for 2 days, followed by infusion of CD19 CAR-T cells after 3-5 days.…”

“…Production of CAR-expressing T cells were produced for the experiments as previously described. 13 Patients and healthy donors provided written informed consents according to the Declaration of Helsinki presented at the International Conference on Harmonization Guidelines for Good Clinical Practice. All relevant ethical regulations were followed in this study.…”

Fatal outcome in a COVID-19 patient despite IL 6 blockage in cytokine storm

“…Solely one case report described a similar clinical aggravation of coagulopathy in a patient receiving TCZ after developing CRS secondary to CAR-T cell therapy and bacterial superinfection was suspected to be responsible. [19] In our patient PCT levels were normal before both administrations and broad spectrum antibiotic was applied prophylactically. Nevertheless, septic shock due to fungal pneumonia cannot be ruled out.…”