Atezolizumab Consolidation in Patients with High Risk Diffuse Large B-cell Lymphoma in Complete Remission after R-CHOP.

IF 7.4 1区医学 Q1 HEMATOLOGY

Blood advances Pub Date : 2025-04-18 DOI:10.1182/bloodadvances.2024015226

Marcel Nijland, Djamila E Issa, Johanna A A Bult, Dries Deeren, Gerjo A Velders, Marten R Nijziel, Yorick Sandberg, Vibeke Kj Vergote, Margriet Oosterveld, Rob Fijnheer, Rolf Brouwer, Rinske Boersma, Kalung Wu, Laurens Nieuwenhuizen, Joost Sp Vermaat, Roel J W van Kampen, Wim E Terpstra, Sylvia Snauwaert, Marjolein Wm van der Poel, Eva de Jongh, Marc Durian, Leonie Strobbe, Aart Beeker, Alain Pa Gadisseur, Roos Van Rijn, Otto J Visser, Jeanette Doorduijn, Tjeerd J F Snijders, Matthijs H Silbermann, Daphne de Jong, Martine E D Chamuleau, Rogier Mous, Mathilde Jalving, Heleen Visser-Wisselaar, Sonja Jansen van den Bergh, Gerben Jc Zwezerijnen, Edwin Bremer, Mirian Brink, Arjan Diepstra, Dana A Chitu, Harry R Koene, Josée M Zijlstra

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引用次数: 0

Abstract

The risk of relapse among high-risk diffuse large B-cell lymphoma (DLBCL) patients in complete metabolic remission (CMR) following R-CHOP therapy is 20-25%. Here, we evaluated whether consolidation with the PDL-1 checkpoint inhibitor atezolizumab could reduce the relapse risk. In this phase II, open-label trial (NCT03463057) DLBCL patients with an international prognostic index (IPI) score of ≥ 3 and CMR after R-CHOP received 1200mg atezolizumab every 3 weeks for 18 cycles. The primary endpoint was disease-free survival (DFS) at 2 years with the aim of improving it to 89% compared to historical 79%. Secondary endpoints included overall survival (OS) and safety (CTCAE version 4.0). Analyses were intention-to-treat. Of 109 patients, 65% completed treatment. The cohort was 59% males, with 63% having high-intermediate risk IPI scores. At a median follow-up of 36.4 months, 15 relapses occurred (median time 8.2 months). The 2-year DFS was 87.9% (90% confidence interval (CI) 81.5-92.1%) and 2-year OS was 96.3% (90% CI 91.7-98.3%) meeting the primary objective. Treatment with salvage chemotherapy resulted in 10/13 patients achieving a second CMR. Compared to a population-based matched control cohort from the Netherlands Cancer Registry, OS was significantly better among atezolizumab-treated patients. Adverse events (AE) affected 79% of patients, with 18% developing immune-related AEs, including 4.5% grade 3-4. Atezolizumab consolidation significantly improved DFS in high-risk DLBCL patients compared to historical cohorts. OS was significantly better compared to a population-based control cohort. These findings warrant further validation and assessment of immune checkpoint inhibitors as consolidation strategy in DLBCL.

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Atezolizumab在R-CHOP后完全缓解的高风险弥漫性大b细胞淋巴瘤患者中的巩固作用

在R-CHOP治疗后完全代谢缓解（CMR）的高风险弥漫大b细胞淋巴瘤（DLBCL）患者复发的风险为20-25%。在这里，我们评估了合并PDL-1检查点抑制剂atezolizumab是否可以降低复发风险。在这项II期开放标签试验（NCT03463057）中，国际预后指数（IPI）评分≥3且R-CHOP后CMR的DLBCL患者每3周接受1200mg atezolizumab治疗，共18个周期。主要终点是2年无病生存率（DFS），目标是将其从历史上的79%提高到89%。次要终点包括总生存期（OS）和安全性（CTCAE版本4.0）。分析是意向治疗。109名患者中，65%完成了治疗。该队列中59%为男性，63%为中高风险IPI评分。中位随访36.4个月，复发15例（中位时间8.2个月）。2年DFS为87.9%(90%置信区间（CI） 81.5-92.1%)， 2年OS为96.3% (90% CI 91.7-98.3%)，满足主要目标。补救性化疗治疗导致10/13例患者实现第二次CMR。与来自荷兰癌症登记处的基于人群的匹配对照队列相比，阿特唑单抗治疗患者的OS明显更好。不良事件（AE）影响了79%的患者，18%的患者发展为免疫相关的AE，其中4.5%为3-4级。与历史队列相比，Atezolizumab巩固显著改善了高风险DLBCL患者的DFS。与基于人群的对照队列相比，OS明显更好。这些发现为进一步验证和评估免疫检查点抑制剂作为DLBCL巩固策略提供了依据。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Blood advances Medicine-Hematology

CiteScore

12.70

自引率

2.70%

发文量

840

期刊介绍： Blood Advances, a semimonthly medical journal published by the American Society of Hematology, marks the first addition to the Blood family in 70 years. This peer-reviewed, online-only, open-access journal was launched under the leadership of founding editor-in-chief Robert Negrin, MD, from Stanford University Medical Center in Stanford, CA, with its inaugural issue released on November 29, 2016. Blood Advances serves as an international platform for original articles detailing basic laboratory, translational, and clinical investigations in hematology. The journal comprehensively covers all aspects of hematology, including disorders of leukocytes (both benign and malignant), erythrocytes, platelets, hemostatic mechanisms, vascular biology, immunology, and hematologic oncology. Each article undergoes a rigorous peer-review process, with selection based on the originality of the findings, the high quality of the work presented, and the clarity of the presentation.