Atezolizumab consolidation in patients with high-risk diffuse large B-cell lymphoma in complete remission after R-CHOP

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.

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Journal
Blood Advances
Published
2025-04-18
DOI
https://doi.org/10.1182/bloodadvances.2024015226
Citations
5
Primary Topic
Lymphoma Diagnosis and Treatment
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article
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7.36
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article

Atezolizumab consolidation in patients with high-risk diffuse large B-cell lymphoma in complete remission after R-CHOP

Rinske Boersma, Roel J.W. van Kampen, Jeanette K. Doorduijn, Daphne de Jong et al.
5 citations
Blood Advances
Lymphoma Diagnosis and Treatment
7.36
article

Atezolizumab consolidation in patients with high-risk diffuse large B-cell lymphoma in complete remission after R-CHOP

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

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.

Blood AdvancesVol. 9(14)
University Medical Center Groningen (NL), Radboud University Nijmegen (NL), Utrecht University (NL), Dutch Cancer Society (NL), Leiden University Medical Center (NL), Universitair Ziekenhuis Leuven (BE), Gelre Hospitals (NL), Catharina Ziekenhuis (NL), Medisch Spectrum Twente (NL), Erasmus MC (NL), Medisch Centrum Leeuwarden (NL), Amsterdam UMC Location University of Amsterdam (NL), The Netherlands Cancer Institute (NL), University Medical Center Utrecht (NL), Maastricht University (NL), Albert Schweitzer Ziekenhuis (NL), Reinier de Graaf Hospital (NL), Spaarne Ziekenhuis (NL), Antwerp University Hospital (BE), St. Antonius Ziekenhuis (NL), OLVG (NL), Amphia Ziekenhuis (NL), Maasstad Ziekenhuis (NL), Inagro (Belgium) (BE), Canisius-Wilhelmina Ziekenhuis (NL), AZ Sint-Jan (BE), Ziekenhuis Gelderse Vallei (NL), Máxima Medisch Centrum (NL), Zuyderland Medisch Centrum (NL), Netherlands Comprehensive Cancer Organisation (NL), AZ Delta (BE), Hovon (NL), Isala (NL), Tergooi (NL), Elisabeth-TweeSteden Ziekenhuis (NL), Erasmus MC Cancer Institute (NL), Ziekenhuisnetwerk Antwerpen Stuivenberg (BE), Amsterdam University Medical Centers (NL), Meander Medisch Centrum (NL), Jeroen Bosch Ziekenhuis (NL), Spaarne Gasthuis (NL), Cancer Center Amsterdam (NL), University of Amsterdam (NL), Erasmus University Rotterdam (NL), KU Leuven (BE)
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Openalex Percentile: Top 3%
Lymphoma Diagnosis and Treatment
7.36
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