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Recent advances in post autologous transplantation maintenance therapies in B-cell non-Hodgkin lymphomas

机译:B细胞非霍奇金淋巴瘤自体移植后维持疗法的最新进展

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摘要

Lymphomas constitute the second most common indication for high dose therapy (HDT) followed by autologous hematopoietic cell transplantation (auto-HCT). The intent of administering HDT in these heterogeneous disorders varies from cure (e.g., in relapsed aggressive lymphomas) to disease control (e.g., most indolent lymphomas). Regardless of the underlying histology or remission status at transplantation, disease relapse remains the number one cause of post auto-HCT therapy failure and mortality. The last decade has seen a proliferation of clinical studies looking at 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. In relapsed, chemosensitive diffuse large B-cell lymphoma (DLBCL), although post auto-HCT maintenance rituximab seems to be safe and feasible, it does not provide improved survival outcomes and is not recommended. The preliminary results with anti- programmed death -1 (PD-1) antibody therapy as post auto-HCT maintenance in DLBCL is promising but requires randomized validation. Similarly in follicular lymphoma, maintenance therapies including rituximab following auto-HCT should be considered investigational and offered only on a clinical trial. Rituximab maintenance results in improved progression-free survival but has not yet shown to improve overall survival in mantle cell lymphoma (MCL), but given the poor prognosis with post auto-HCT failure in MCL, maintenance rituximab can be considered on a case-by-case basis. Ongoing trials evaluating the efficacy of post auto-HCT maintenance with novel compounds (e.g., immunomodulators, PD-1 inhibitors, proteasome inhibitors and bruton’s tyrosine kinase inhibitors) will likely change the practice landscape in the near future for B cell non-Hodgkin lymphomas patients following HDT and auto-HCT.
机译:淋巴瘤是高剂量治疗(HDT)其次是自体造血细胞移植(auto-HCT)的第二大最常见适应症。在这些异质性疾病中施用HDT的意图从治愈(例如复发性侵袭性淋巴瘤)到疾病控制(例如大多数惰性淋巴瘤)不等。不论移植时的基本组织学或缓解状态如何,疾病复发仍然是导致自动HCT治疗失败和死亡的首要原因。在过去的十年中,通过各种维持策略来预防自身HCT治疗后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。在复发,化学敏感的弥漫性大B细胞淋巴瘤(DLBCL)中,尽管自动HCT术后维持利妥昔单抗似乎是安全可行的,但不能提高生存率,因此不建议使用。抗程序性死亡-1(PD-1)抗体疗法作为DLBCL中自身HCT后维持的初步结果是有希望的,但需要随机验证。类似地,在滤泡性淋巴瘤中,auto-HCT后包括利妥昔单抗在内的维持治疗应被认为是研究性的,仅在临床试验中提供。利妥昔单抗维持治疗可改善无进展生存期,但尚未显示出改善套细胞淋巴瘤(MCL)的总体生存率,但是鉴于MCL的自动HCT失败后预后较差,可以逐例考虑维持利妥昔单抗案例的基础上。正在进行的评估新型化合物(例如免疫调节剂,PD-1抑制剂,蛋白酶体抑制剂和布鲁顿酪氨酸激酶抑制剂)在自动HCT后维持疗效的试验可能会在不久的将来改变B细胞非霍奇金淋巴瘤患者的治疗前景跟随HDT和自动HCT。

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