Marcel Nijland, Djamila E Issa, Johanna A A Bult, Dries Deeren, Gerjo A Velders, Marten R Nijziel, Yorick Sandberg, Vibeke Vergote, Margriet Oosterveld, Rob Fijnheer, Rolf E Brouwer, Rinske S Boersma, Kalung Wu, Laurens Nieuwenhuizen, Joost S P Vermaat, Roel J W van Kampen, Wim E Terpstra, Sylvia Snauwaert, Marjolein W van der Poel, Eva de Jongh, Marc F Durian, Leonie Strobbe, Aart Beeker, Alain Gadisseur, Roos S van Rijn, Otto Visser, Jeanette K Doorduijn, Tjeerd J F Snijders, Matthijs H Silbermann, Daphne de Jong, Martine Chamuleau, Rogier Mous, Hilde Jalving, Heleen Visser-Wisselaar, Sonja Jansen van de Bergh, Gerben J C Zwezerijnen, Edwin Bremer, Mirian Brink, Arjan Diepstra, Dana A Chitu, Harry R Koene, Josée M Zijlstra
{"title":"Atezolizumab consolidation in patients with high-risk diffuse large B-cell lymphoma in complete remission after R-CHOP.","authors":"Marcel Nijland, Djamila E Issa, Johanna A A Bult, Dries Deeren, Gerjo A Velders, Marten R Nijziel, Yorick Sandberg, Vibeke Vergote, Margriet Oosterveld, Rob Fijnheer, Rolf E Brouwer, Rinske S Boersma, Kalung Wu, Laurens Nieuwenhuizen, Joost S P Vermaat, Roel J W van Kampen, Wim E Terpstra, Sylvia Snauwaert, Marjolein W van der Poel, Eva de Jongh, Marc F Durian, Leonie Strobbe, Aart Beeker, Alain Gadisseur, Roos S van Rijn, Otto Visser, Jeanette K Doorduijn, Tjeerd J F Snijders, Matthijs H Silbermann, Daphne de Jong, Martine Chamuleau, Rogier Mous, Hilde Jalving, Heleen Visser-Wisselaar, Sonja Jansen van de Bergh, Gerben J C Zwezerijnen, Edwin Bremer, Mirian Brink, Arjan Diepstra, Dana A Chitu, Harry R Koene, Josée M Zijlstra","doi":"10.1182/bloodadvances.2024015226","DOIUrl":null,"url":null,"abstract":"<p><strong>Abstract: </strong>The risk of relapse among high-risk patients with diffuse large B-cell lymphoma (DLBCL) in complete metabolic remission (CMR) after rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisolone (R-CHOP) therapy is 20% to 25%. Here, we evaluated whether consolidation with the programmed cell death ligand 1 checkpoint inhibitor atezolizumab could reduce the relapse risk. In this phase 2, open-label trial, patients with DLBCL with an International Prognostic Index (IPI) score of ≥3 and CMR after R-CHOP received 1200 mg atezolizumab every 3 weeks for 18 cycles. The primary end point was disease-free survival (DFS) at 2 years, with the aim of improving it to 89% compared to historical 79%. Secondary end points included overall survival (OS) and safety (Common Terminology Criteria for Adverse Events version 4.0). Analyses were on an intention-to-treat principle. 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, 8.2 months). The 2-year DFS was 87.9% (90% confidence interval [CI], 81.5-92.1), and the 2-year OS was 96.3% (90% CI, 91.7-98.3), meeting the primary objective. Treatment with salvage chemotherapy resulted in 10 of 13 patients achieving a second CMR. OS was significantly better among atezolizumab-treated patients than in a population-based matched control cohort from the Netherlands Cancer Registry. Adverse events (AEs) affected 79% of patients, with 18% developing immune-related AEs, including 4.5% grade 3 to 4. Atezolizumab consolidation significantly improved DFS in high-risk patients with DLBCL compared to historical cohorts. OS was significantly better than a population-based control cohort. These findings warrant further validation and assessment of immune checkpoint inhibitors as consolidation strategy in DLBCL. This trial was registered at www.clinicaltrials.gov as #NCT03463057.</p>","PeriodicalId":9228,"journal":{"name":"Blood advances","volume":" ","pages":"3530-3539"},"PeriodicalIF":7.4000,"publicationDate":"2025-07-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12274673/pdf/","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Blood advances","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1182/bloodadvances.2024015226","RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"HEMATOLOGY","Score":null,"Total":0}
引用次数: 0
Abstract
Abstract: The risk of relapse among high-risk patients with diffuse large B-cell lymphoma (DLBCL) in complete metabolic remission (CMR) after rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisolone (R-CHOP) therapy is 20% to 25%. Here, we evaluated whether consolidation with the programmed cell death ligand 1 checkpoint inhibitor atezolizumab could reduce the relapse risk. In this phase 2, open-label trial, patients with DLBCL with an International Prognostic Index (IPI) score of ≥3 and CMR after R-CHOP received 1200 mg atezolizumab every 3 weeks for 18 cycles. The primary end point was disease-free survival (DFS) at 2 years, with the aim of improving it to 89% compared to historical 79%. Secondary end points included overall survival (OS) and safety (Common Terminology Criteria for Adverse Events version 4.0). Analyses were on an intention-to-treat principle. 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, 8.2 months). The 2-year DFS was 87.9% (90% confidence interval [CI], 81.5-92.1), and the 2-year OS was 96.3% (90% CI, 91.7-98.3), meeting the primary objective. Treatment with salvage chemotherapy resulted in 10 of 13 patients achieving a second CMR. OS was significantly better among atezolizumab-treated patients than in a population-based matched control cohort from the Netherlands Cancer Registry. Adverse events (AEs) affected 79% of patients, with 18% developing immune-related AEs, including 4.5% grade 3 to 4. Atezolizumab consolidation significantly improved DFS in high-risk patients with DLBCL compared to historical cohorts. OS was significantly better than a population-based control cohort. These findings warrant further validation and assessment of immune checkpoint inhibitors as consolidation strategy in DLBCL. This trial was registered at www.clinicaltrials.gov as #NCT03463057.
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.
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