[Sequential therapy with inotuzumab ozogamicin followed by CAR T-cell therapy for Philadelphia chromosome-negative acute lymphoblastic leukemia].

Yo Mizutani, Shinsuke Kusakabe, Kentaro Fukushima, Hiraku Murakami, Masataka Hamada, Chihiro Hasegawa, Emiko Mizuta, Yuta Yamaguchi, Ritsuko Nakai, Ryumei Kurashige, Akihisa Hino, Tomoaki Ueda, Jiro Fujita, Takako Miyamura, Naoki Hosen
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Abstract

A 25-year-old woman with a history of B-cell acute lymphoblastic leukemia over ten years ago was referred to our hospital with a chief complaint of leukoblastosis. She was participating in a JPLSG (Japanese Pediatric Leukemia/Lymphoma Study Group) clinical study at that time. We diagnosed ALL relapse by multi-color flow cytometric analysis of bone marrow samples at admission, with reference to previous JPLSG data. Because her leukemic cells were resistant to conventional cytotoxic agents, she proceeded to lymphocyte apheresis for chimeric antigen receptor T-cell (CAR-T, Tisagenlecleucel [Tisa-cel]). She received two cycles of inotuzumab ozogamicin as a bridging therapy to Tisa-cel, resulting in a hematological complete remission (minimal residual disease measured by polymerase chain reaction [PCR-MRD] was positive at 1.0×10-4). She was finally administered Tisa-cel and achieved MRD negativity. She is currently in complete remission with careful MRD monitoring. This strategy of sequential bi-targeted therapy combining antibody conjugates and CAR-T cells provides tumor control in deeper remission and minimal damage to organ function through reduced use of cytotoxic anti-tumor agents. Therefore, we believe that this therapeutic strategy is an effective and rational treatment for adolescent and young adult ALL patients.

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[费城染色体阴性急性淋巴细胞白血病患者使用伊妥珠单抗-奥佐加米星(inotuzumab ozogamicin)进行序贯治疗后,再使用 CAR T 细胞疗法]。
一名十多年前曾患过 B 细胞急性淋巴细胞白血病的 25 岁女性因主诉白细胞增多症被转诊到我院。她当时正在参加 JPLSG(日本儿童白血病/淋巴瘤研究小组)的临床研究。入院时,我们通过对骨髓样本进行多色流式细胞分析,并参考之前的 JPLSG 数据,诊断为 ALL 复发。由于她的白血病细胞对常规细胞毒药物具有抗药性,因此她接受了嵌合抗原受体T细胞(CAR-T,Tisagenlecleucel [Tisa-cel])淋巴细胞分离术。她接受了两个周期的伊妥珠单抗-奥佐加米星(inotuzumab ozogamicin)治疗,作为Tisa-cel的桥接疗法,结果血液学完全缓解(聚合酶链反应[PCR-MRD]测定的最小残留病为阳性,为1.0×10-4)。最后,她接受了 Tisa-cel 治疗,MRD 阴性。目前,她的病情完全缓解,MRD 也得到了仔细监测。这种结合抗体共轭物和 CAR-T 细胞的序贯双靶向治疗策略可在较深的缓解期控制肿瘤,并通过减少细胞毒性抗肿瘤药物的使用将对器官功能的损害降至最低。因此,我们认为这种治疗策略对青少年和年轻成人 ALL 患者来说是一种有效而合理的治疗方法。
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