血管免疫母细胞性 T 细胞淋巴瘤 (AITL) 是一种外周 T 细胞淋巴瘤，其特征是滤泡辅助性 T 细胞表达 PD-1（程序性细胞死亡-1）表型。 AITL 对传统化疗的反应较差，中位 5 年总生存率为 44%，无进展生存率为 32%。复发很常见，中位总生存期为 6 个月。在调节 DNA 甲基化的基因中检测到反复发生的突变，包括 TET2、DNMT3A 和 IDH2 变体，以及普遍的 RHOA G17V 突变。在这种情况下，接受低甲基化药物 5-氮杂胞苷治疗的患者的总体缓解率和完全缓解率分别为 75% 和 41%。我们假设，结合抗 PD-1 检查点阻断剂和低甲基化药物的靶向治疗可能对 AITL 患者有效，并且比标准化疗的毒性更小。在此，我们报告了 5-氮杂胞苷和纳武利尤单抗联合治疗方案对 9 例复发或难治性 AITL 的疗效该方案耐受性良好，尤其是老年患者。总体答复率为 78%，其中部分答复 4 份（44%），完全答复 3 份（33%）。对两名达到完全缓解的患者进行了同种异体造血干细胞移植。这些初步良好的结果可以作为前瞻性研究进一步调查的基础。版权所有 © 2024 Ricard, Cervera, Stocker, Corre, Van de Wyngaert, Banet, Marjanovic,杜勒里、布拉维蒂、乔利、贝拉特里和科波。

Angioimmunoblastic T-cell lymphoma (AITL) is a peripheral T-cell lymphoma characterized by a T follicular helper cell phenotype expressing PD-1 (programmed cell death-1). AITL exhibits a poor response to conventional chemotherapy, with a median 5-year overall survival of 44% and a progression-free survival of 32%. Relapse is common, resulting in a median overall survival of 6 months. Recurrent mutations are detected in genes regulating DNA methylation, including TET2, DNMT3A, and IDH2 variants, along with the prevalent RHOA G17V mutation. In this context, patients treated with the hypomethylating agent 5-azacytidine achieved overall response and complete response rates of 75% and 41%, respectively. We hypothesized that targeted therapies combining anti-PD-1 checkpoint blockers with hypomethylating agents could be efficient in AITL patients and less toxic than standard chemotherapy.Here, we report the efficacy of a regimen combining 5-azacytidine and nivolumab in nine relapsed or refractory AITL patients.This regimen was well-tolerated, especially in elderly patients. The overall response rate was 78%, including four partial responses (44%) and three complete responses (33%). Allogeneic hematopoietic stem cell transplantation was performed in two patients who reached complete response.These preliminary favorable results may serve as a basis for further investigation in prospective studies.Copyright © 2024 Ricard, Cervera, Stocker, Corre, Van de Wyngaert, Banet, Marjanovic, Dulery, Bravetti, Joly, Baylatry and Coppo.