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Post-autologous transplant maintenance therapies in lymphoid malignancies: are we there yet?

机译:淋巴恶性肿瘤的自体移植后维持疗法:我们到了吗?

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Disease relapse after autologous hematopoietic transplant (auto-HCT) remains the number one cause of post-transplant therapy failure and mortality. The last decade has seen a proliferation of clinical studies looking at the prevention of post-auto-HCT therapy failure with various maintenance strategies. The benefit of such therapies is in turn dependent on disease histology and timing of transplantation. Although high dose therapy (HDT) provides durable responses in chemosensitive relapsed diffuse large B-cell lymphoma (DLBCL), a sizable subset experiences disease relapse. Unfortunately, the addition of rituximab as a post-auto-HCT maintenance strategy did not improve survival outcomes. The preliminary results with programmed death -1 (PD-1) Ab as post-auto maintenance in DLBCL is promising but requires randomized validation. In follicular lymphoma, the 5-and 10-year PFS rates are similar to 60% and 31%, respectively. Although the addition of rituximab improved PFS, there is no survival benefit, to date. Disease relapse after auto-HCT in mantle cell lymphoma (MCL) is not uncommon. Rituximab maintenance in this setting provides a PFS benefit. Given the poor prognosis of post-auto-HCT failures in MCL, maintenance can be considered on a case-by-case basis. In chemosensitive relapsed Hodgkin lymphoma, addition of brentuximab vedotin after auto-HCT improved 2-year PFS (65 vs 45%) and can be considered as an option for maintenance therapy post auto-HCT, in select higher risk patients. Ongoing trials evaluating the efficacy of post-auto-HCT maintenance with novel agents (for example, immunomodulators, proteasome inhibitors, PD-1 inhibitors, Bruton's tyrosine kinase inhibitors and so on) will likely change the practice landscape for lymphoma patients following HDT and auto-HCT.
机译:自体造血干细胞移植(auto-HCT)后的疾病复发仍然是移植后治疗失败和死亡率的第一原因。在过去的十年中,通过各种维持策略来预防自动HCT治疗失败的临床研究激增。这种疗法的益处反过来取决于疾病的组织学和移植的时机。尽管高剂量疗法(HDT)在化学敏感性复发弥漫性大B细胞淋巴瘤(DLBCL)中提供了持久的反应,但相当大的一部分经历了疾病的复发。不幸的是,将利妥昔单抗作为HCT后自动维持策略并不能改善生存结果。在DLBCL中将程序性死亡-1(PD-1)Ab作为汽车后维护的初步结果是有希望的,但需要随机验证。在滤泡性淋巴瘤中,5年和10年的PFS率分别接近60%和31%。尽管添加利妥昔单抗可改善PFS,但迄今为止尚无生存获益。上皮细胞淋巴瘤(MCL)的自身HCT引起的疾病复发并不罕见。在这种情况下利妥昔单抗维持治疗可提供PFS益处。鉴于MCL中自动HCT后故障的不良预后,可以根据具体情况考虑进行维护。在对化学敏感性复发的霍奇金淋巴瘤中,在自动HCT后加入brentuximab vedotin可以改善2年PFS(65 vs 45%),对于某些较高风险的患者,可以考虑在自动HCT后进行维持治疗。正在进行的评估使用新型药物(例如免疫调节剂,蛋白酶体抑制剂,PD-1抑制剂,Bruton酪氨酸激酶抑制剂等)进行自动HCT维持疗效的试验可能会改变HDT和自动疗法后淋巴瘤患者的实践前景-HCT。

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