Clinical analysis of chimeric antigen receptor T cells immunotherapy in treatment of one patient with relapsed/refractory primary central nervous system lymphoma

Abstract

Objective \nTo investigate the indications, complications and prognosis of chimeric antigen receptor T cells (CAR-T) in the treatment of relapsed/refractory primary central nervous system lymphoma (PCNSL). \n \n \nMethods \nOn May 21, 2015, one patient with relapsed/refractory PNCSL admitted to the Department of Hematology, Xuzhou Medical University Affiliated Hospital was selected as the study object. The peripheral blood lymphocytes of the patient were collected by blood cell apheresis, and humanized CD19 and CD20 CAR-T were prepared. CAR is stably expressed in CD3+ T cells via lentiviral vector. On July 27, 2017, the patient received FC regimen of conditioning regimen by fludarabine 30 mg/(m2·d), d-5 to -3, and cyclophosphamide 750 mg/(m2·d), d-5. Humanized CD19 and CD20 CAR-T were transfused with dose of 1×106/kg each, on the first day after conditioning regimen. The clinical features and diagnosis of the patient were summarized by retrospective analysis. This study was in line with World Medical Association Declaration of Helsinki revised in 2013 and informed contents of clinical research and CAR-T immunotherapy were obtained from the subject. \n \n \nResults \n① The patient was male and 45 years old. In February 2015, the patient appeared headache, dizziness, and blindness in the right eye without obvious incentives. In March 2015, the patient was diagnosed with diffuse large B-cell lymphoma based on his pathology and immunohistochemistry results. In January 2016, the patient achieved unconfirmed complete remission (CRu) after surgical removal of the corpus callosum, radiotherapy, and high-dose radiation therapy. In March 2017, the patient′s primary disease recurred, but the condition was relieved after receiving temozolomide+ high-dose methotrexate(HD-MTX) chemotherapy. ②After 10 d of CAR-T infusion, the patient′s headache symptoms were significantly reduced and the orientation was recovery. Grade 1 cytokine release syndrome(CRS) occurred during treatment. Patient′s symptoms improved after he received symptomatic supportive treatment. After 29, 69 and 116 d of CAR-T transfusion, the results of patient′s head-enhanced MRI showed that the primary lesion continued to shrink. And the patient reached partial remission (PR). After 69 and 116 d of CAR-T transfusion, CAR-T were detected in cerebrospinal fluid flow cytometry of patient. After 154 d of CAR-T transfusion, the patient returned to hospital for treatment, due to left limb weakness . Re-examination of head-enhanced MRI showed recurrence of primary disease. Then the patient received salvage treatment of high-dose chemotherapy. As of July 2019, the patient was still receiving temozolomide + HD-MTX chemotherapy for maintenance treatment. \n \n \nConclusions \nAs a new treatment regimen, CAR-T immunotherapy could be used as a salvage bridging treatment in the treatment of patients with relapsed/refractory PCNSL. And it is still necessary to maintain and consolidate the treatment. However, the above conclusions are based on one case study, and the maintenance treatment of patients with relapsed/refractory PCNSL after CAR-T immunotherapy, such as the time of maintenance treatment beginning , as well as the maintenance treatment regimen, still need to be further explored. \n \n \nKey words: \nLymphoma, non-Hodgkin;\xa0Lymphoma, large B-cell, diffuse;\xa0Receptors, chimeric antigen;\xa0Primary central nervous system lymphoma;\xa0Recurrence;\xa0Refractory;\xa0Chimeric antigen receptor T cells;\xa0Immunotherapy