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.

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Anti-CD19 chimeric antigen receptor T cell (CAR-T) therapy has changed the typical outcomes of relapsed/refractory B-cell leukemia and lymphoma. However, treatment effectiveness for patients with relapsed/refractory B-cell non-Hodgkin lymphoma has been less satisfactory compared with patients with B-cell acute lymphoblastic leukemia. The present study described a case of refractory follicular lymphoma. A high expression of programmed cell death 1 (PD-1) was measured on CD3+ T cells (80.90%) in peripheral blood samples obtained from the patient enrolled in this study, indicating that treatment with autologous CAR-T 19 cell therapy may not be successful. Therefore, a therapy regimen consisting of CAR-T 19 cells in combination with a reduced dose of nivolumab (1.5 mg/kg) for PD-1 blockade was used. A low dose of PD-1 blockade therapy was used to reduce the adverse effects associated with the combination of a PD-1 inhibitor and CAR-T 19 cells. This salvage therapy resulted in remission that lasted for >10 months.

The efficacy and side effects of the second‐time humanized CD19 chimeric antigen receptor (CD19‐CAR) T‐cell therapy after unsuccessful first‐time anti‐CD19‐CAR T‐cell therapy and subsequent ibrutinib salvage treatment were observed in patients with refractory B‐cell lymphoma. In our study, 3 patients with refractory mantle cell lymphoma (MCL) and 4 patients with refractory follicular lymphoma (FL) reached stable disease (SD), partial remission (PR), or progression of disease (PD) after first‐time humanized anti‐CD19‐CAR T‐cell therapy. They received ibrutinib as a salvage treatment and kept an SD in the following 7‐16 mo, but their disease progressed again during ibrutinib salvage treatment. All 7 patients received a second‐time humanized anti‐CD19‐CAR T‐cell therapy, which was the same as their first‐time anti‐CD19‐CAR T‐cell therapy. In total, 3 MCL patients and 3 FL patients reached complete response (CR) with the second‐time anti‐CD19‐CAR T‐cell therapy combined with ibrutinib, whereas 1 FL patient reached PR. There were no differences in the transduction efficiency and proliferation between the 2 instances of anti‐CD19‐CAR T‐cell therapy. However, the second‐time anti‐CD19‐CAR T‐cell therapy led to higher peaks of anti‐CD19‐CAR T cells and anti‐CD19‐CAR gene copies, but also to higher grades of cytokine release syndrome (CRS) and more serious hematological toxicity. The successful outcome of the second‐time anti‐CD19‐CAR T‐cell therapy might suggest that the previous ibrutinib treatment improved the activities of anti‐CD19‐CAR T cells.