Immunophenotypic transformation in relapsed/refractory mantle cell lymphoma treated with human anti-CD5 chimeric antigen receptor T cells: A Case Report

Shan He, X. Mao, Zhaoting Cheng, Xiaojian Zhu, M. Xiao, J. Zhou
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Abstract

Relapsed/refractory (R/R) mantle cell lymphoma (MCL) with primary drug resistance to Bruton tyrosine kinase inhibitor and mutated TP53 responds poorly to conventional treatments. Chimeric antigen receptor (CAR) T cell therapy has emerged as one of the most effective treatments for R/R B cell lymphoma. However, no reports of CD5 CAR T cell treatment for MCL have been reported. In this paper, we report a R/R MCL patient with primary drug resistance to BTK inhibitors and TP53 mutation enrolled in a human CD5 CAR T cell trial. Remission of the primary disease was observed half a month after CAR T cell infusion. However, ascites was observed 2 weeks later. Flow cytometry suggested disease progression and immunophenotypic transformation. CD5 in CAR T cells turned negative and the expression of CD38 was enhanced. The patient was treated with a combination of daratumumab and Gemox (gemcitabine + oxaliplatin), abdominal distension and pain were markedly reduced, and ascites disappeared. We report the first case of human CD5 CAR T cell treatment for a patient with R/R MCL, providing insight on treatment strategies for such patients.
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人抗cd5嵌合抗原受体T细胞治疗复发/难治性套细胞淋巴瘤的免疫表型转化:一例报告
复发/难治性(R/R)套细胞淋巴瘤(MCL)对布鲁顿酪氨酸激酶抑制剂和突变TP53的原发性耐药对常规治疗反应不佳。嵌合抗原受体(CAR) T细胞疗法已成为R/R B细胞淋巴瘤最有效的治疗方法之一。然而,目前还没有关于CD5 CAR - T细胞治疗MCL的报道。在这篇论文中,我们报道了一名原发性BTK抑制剂耐药和TP53突变的R/R MCL患者参加了一项人类CD5 CAR - T细胞试验。CAR - T细胞输注后半个月观察原发疾病的缓解。2周后出现腹水。流式细胞术提示疾病进展和免疫表型转化。CAR - T细胞中CD5转为阴性,CD38表达增强。患者经达拉单抗联合Gemox(吉西他滨+奥沙利铂)治疗,腹胀、疼痛明显减轻,腹水消失。我们报告了首例人类CD5 CAR - T细胞治疗R/R MCL患者的病例,为此类患者的治疗策略提供了见解。
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