Plasma Exchange Can Be an Alternative Therapeutic Modality for Severe Cytokine Release Syndrome after Chimeric Antigen Receptor-T Cell Infusion: A Case Report

Abstract

Background: Tumor immunotherapy with chimeric antigen receptor-T cells (CAR-T) is a promising new treatment for B-cell malignancies and has produced exciting results. However, cytokine release syndrome (CRS) is the most significant toxicity associated with this treatment and can be lifethreatening. Case Presentation: A 23-year-old male patient had been diagnosed with relapsed and refractory B-cell acute lymphocytic leukemia. The patient was recruited into our CART clinical trial, and 1 Â 10 6 /kg of engineered anti-CD19 CART cells was administered. After infusion of CART cells (day 0), the patient underwent a typical CRS reaction, with increases in fever, muscle soreness, and inflammatory cytokines. He was treated with antiallergic and antipyretic drugs, glucocorticoids, and tocilizumab (4 mg/kg, days 3 and 5). However, CRS was not under control, and his condition rapidly deteriorated. He was transferred to the intensive care unit, where dexamethasone 10 mg q6h was administered, and plasma exchange was performed, with 3,000 mL of plasma replaced by fresh frozen plasma per day for 3 consecutive days. His symptoms gradually improved, and the CRS-related symptoms were relieved. Additionally, a bone marrow smear showed no lymphoblast cells, and minimal residual disease was negative on day 28. The patient was eventually discharged in a normal condition. Conclusions: CRS is caused by an exaggerated systemic immune response, potentially resulting in organ damage that can be fatal. Although therapeutic plasma exchange is not included in CRS management guidelines, this case shows that plasma exchange is feasible in at least some patients with severe CRS.

Potential Treatments for COVID-19 Related Cytokine Storm - Beyond Corticosteroids

“…Ruxolitinib was also well-tolerated in patients with severe COVID-19, indicating ruxolitinib could be safely used to treat patients with COVID-19 (21). Additionally, therapeutic plasma exchange can reduce the plasma cytokine concentrations rapidly, and has been successfully used to treat HLH and CRS related to CAR T cells infusion (22,23), suggesting plasma exchange may be a reasonable option for severe patients with cytokine storm. In a preliminary study, therapeutic plasma exchange reduced the plasma IL-6 level and improved the oxygenation status in patients with severe COVID-19 who had ARDS (24).…”

HLA-matched and HLA-haploidentical allogeneic CD19-directed chimeric antigen receptor T-cell infusions are feasible in relapsed or refractory B-cell acute lymphoblastic leukemia before hematopoietic stem cell transplantation

“…After three therapeutic plasma exchange cycles, patient 2 recovered consciousness, and both the fever and inflammatory indicators improved. We have reported the specific clinical course of patient in the form of a case report [4]. All patients developed fever after HCART19 cell infusion; nonetheless, in contrast to the MCART19 cell-treated patients, the HCART19 cell-treated patients experienced transient fever that could be controlled by antiallergy and antipyretic drugs.…”

Efficacy of therapeutic plasma exchange in the treatment of penn class 3 and 4 cytokine release syndrome complicating COVID-19

“…Huang [ 10 ] reported excessive elaboration of IL-2, IL-10, TNFα and macrophage inflammatory protein 1-alpha among others, while Mehta et al [ 11 ] noted the resemblance of severe COVID-19 expression to secondary hemophagocytic lymphohistiocytosis (sHLH) with its potentially fatal hypercytokinemic state. Additionally, TPE has been shown to have clinical benefit in various hypercytokinemic states including CRS following CAR T-cell treatment [ 12 ] and in pH1N1 influenza A respiratory failure and hemodynamic shock [ 13 ].…”