决定异体 CAR T 细胞排斥与扩增的细胞和分子机制
Cellular and molecular mechanisms determining allogeneic CAR T cell rejection and expansion.
我们评估了11例接受单一批次cemacabtagene ansegedleucel(cema-cel)治疗的大B细胞淋巴瘤患者,cemacabtagene ansegedleucel是一种异体抗CD19 CAR T产品。
英文原题:Guided by target selection, inotuzumab ozogamicin successfully salvaged a patient with refractory follicular lymphoma after anti-CD19 and anti-CD22 CAR T-cell therapy: a case report and literature review.
Guided by target selection, inotuzumab ozogamicin successfully salvaged a patient with refractory follicular lymphoma after anti-CD19 and anti-CD22 CAR T-cell therapy: a case report and literature review.
一名 69 岁男性患者被诊断为难治性滤泡性淋巴瘤(FL),其胸腔积液中 43.6% 的异常 B 淋巴细胞表达 CD20-、CD19+、CD22+。
尽管嵌合抗原受体(CAR)T细胞疗法在复发/难治性(R/R)B细胞非霍奇金淋巴瘤中取得较高缓解率,但治疗无应答或再次进展患者预后仍差。本病例为一名69岁难治性滤泡性淋巴瘤男性患者,胸腔积液中43.6%的异常B淋巴细胞表现为CD20阴性、CD19阳性、CD22阳性。患者在本院接受抗CD19 CAR-T联合抗CD22 CAR-T治疗,但输注两个月后仅达到疾病稳定。疾病再次进展时,胸腔积液中40.2%的异常B淋巴细胞表现为CD19阴性、CD20阴性、CD22阳性。由于当时淋巴瘤细胞仅表达CD22,研究者选择减量奥加伊妥珠单抗(InO)作为挽救治疗(第1、8、15天各1 mg)。主要不良事件为血液学毒性。InO挽救治疗两个月后患者评估达到完全缓解(CR),血液学毒性在随后六个月逐渐恢复。截至目前,该难治性滤泡性淋巴瘤患者持续完全缓解,自InO挽救治疗后无事件生存超过三年。InO可能是CAR-T治疗失败的难治性滤泡性淋巴瘤患者有效且可行的挽救治疗。此外,通过选择淋巴瘤细胞所表达的靶点,可实现R/R B细胞非霍奇金淋巴瘤的免疫治疗。
Although Chimeric antigen receptor (CAR) T-cell therapy has achieved a high response rate in recurrent/refractory (R/R) B-cell non-Hodgkin lymphoma (NHL), the prognosis of the patients who do not respond to this therapy or have a disease progression again is poor. A 69-year-old male patient was diagnosed with refractory follicular lymphoma (FL) had 43.6% abnormal B lymphocytes expressing CD20-, CD19+, CD22 + in his pleural effusion. He received anti-CD19 CAR T-cell combined with anti-CD22 CAR T-cell therapy in our hospital, but he achieved stable disease (SD) only two months after CAR-T cell infusion. When his disease progressed again, there were 40.2% abnormal B lymphocytes expressing CD19-, CD20-, CD22 + in pleural effusion. Because CD22 was the only antigen expressed on his lymphoma cells at this time, reduced-dose of Inotuzumab Ozogamicin (InO) was chosen as a salvage therapy (InO 1 mg on day 1, 8, 15). The main adverse events (AE) of this salvage therapy were haematological toxicity. He was evaluated as complete remission (CR) two months after InO salvage therapy. His haematological toxicity was gradually recovered in the following six months. To date, this refractory FL patient has achieved continuous CR and maintained more than three years of event-free survival from the salvage therapy of InO. InO might be an effective and feasible salvage therapy for refractory FL patients who have failed to CAR-T cell therapy. Moreover, immunotherapy of R/R B-cell NHL could be achieved through target selection of lymphoma cells.
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