Department of Hematology/Oncology, Vanderbilt-Ingram Cancer Center, Nashville, USA;.
Department of Hemato-Oncology, Hôpital Saint-Louis, Paris, France.
Ann Oncol. 2017 Nov 1;28(11):2680-2690. doi: 10.1093/annonc/mdx358.
Maintenance therapy has proven efficacy in indolent non-Hodgkin lymphoma (NHL), yet its role in diffuse large B-cell lymphoma (DLBCL) is an area of ongoing investigation. While DLBCL is potentially curable, >30% of patients relapse following front-line therapy and have a poor prognosis, especially those with refractory disease. Maintenance therapy holds promise to maintain response post-induction.
Keyword searches were carried out in PubMed and congress abstracts of 'diffuse large B-cell lymphoma' and 'maintenance' and focused on phase II/III studies of maintenance following front-line induction.
Although used in indolent forms of NHL, studies of maintenance therapy with rituximab in patients with DLBCL responding to front-line R-CHOP (rituximab/cyclophosphamide/doxorubicin/vincristine/prednisone) have not improved efficacy and are not recommended. Targeted agents enzastaurin and everolimus reported results from the phase III studies PRELUDE and PILLAR-2, respectively, both of which showed no proven maintenance benefit following front-line chemoimmunotherapy induction. Overall, the reported efficacy results with these agents in the maintenance setting do not outweigh the risks. Lenalidomide for maintenance has been reported in three studies. Results from two phase II trials on lenalidomide maintenance revealed positive outcomes in higher-risk patients following induction, resulting in improved progression-free survival in relapsed DLBCL patients who were ineligible for transplantation. First analysis from the phase III REMARC trial showed a significant improvement in progression-free survival for lenalidomide versus placebo, with no difference in overall survival, following front-line R-CHOP induction in elderly patients.
Based on currently available studies of DLBCL maintenance therapies, initial results in front-line, as well as the relapsed setting, with immunomodulators such as lenalidomide show promise for further research to identify appropriate patients who would most benefit. Overall, this review of maintenance studies underscores the need for additional analyses of patient subtypes, clinical risk status, and molecular profiles, with careful consideration of study end points.
维持治疗已被证明对惰性非霍奇金淋巴瘤（NHL）有效，但在弥漫性大 B 细胞淋巴瘤（DLBCL）中的作用仍在研究中。虽然 DLBCL 有治愈的可能，但>30%的患者在一线治疗后复发，预后较差，尤其是那些难治性疾病患者。维持治疗有望在诱导后保持反应。
在 PubMed 中进行了关键词搜索，并在“弥漫性大 B 细胞淋巴瘤”和“维持”的会议摘要中进行了搜索，重点是一线诱导后维持的 II/III 期研究。
虽然在惰性 NHL 中使用，但在对一线 R-CHOP（利妥昔单抗/环磷酰胺/多柔比星/长春新碱/泼尼松）有反应的 DLBCL 患者中使用利妥昔单抗进行维持治疗的研究并未提高疗效，因此不推荐使用。靶向药物恩扎鲁胺和依维莫司分别在 III 期研究 PRELUDE 和 PILLAR-2 中报告了结果，这两项研究均表明在前线化疗免疫诱导后没有证明维持治疗的获益。总体而言，这些药物在维持治疗中的疗效结果并不超过风险。已有三项研究报告了来那度胺用于维持治疗。两项来那度胺维持治疗的 II 期试验结果显示，在诱导后高危患者中具有阳性结果，导致不适合移植的复发 DLBCL 患者的无进展生存期得到改善。III 期 REMARC 试验的首次分析显示，在前一线 R-CHOP 诱导后，与安慰剂相比，来那度胺在老年患者中显著改善了无进展生存期，总生存期无差异。
根据目前关于 DLBCL 维持治疗的研究，在一线以及复发环境中，免疫调节剂如来那度胺的初步结果显示出进一步研究的前景，以确定最受益的合适患者。总体而言，对维持性研究的回顾强调了需要对患者亚组、临床风险状况和分子谱进行进一步分析，并仔细考虑研究终点。
