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

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

doi:10.1182/bloodadvances.2024015226

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

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 JonghMarc 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

^*Corresponding author for this work

Onco-Immunology (O-I)

Research output: Contribution to journal › Article › Academic › peer-review

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.

Original language	English
Journal	Blood Advances
DOIs	https://doi.org/10.1182/bloodadvances.2024015226
Publication status	E-pub ahead of print - 18-Apr-2025

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Nijland, M., Issa, D. E., Bult, J. A. A., Deeren, D., Velders, G. A., Nijziel, M. R., Sandberg, Y., Vergote, V. K., Oosterveld, M., Fijnheer, R., Brouwer, R., Boersma, R., Wu, K., Nieuwenhuizen, L., Vermaat, J. S., van Kampen, R. J. W., Terpstra, W. E., Snauwaert, S., van der Poel, M. W., ... Zijlstra, J. M. (2025). Atezolizumab Consolidation in Patients with High Risk Diffuse Large B-cell Lymphoma in Complete Remission after R-CHOP. Blood Advances. Advance online publication. https://doi.org/10.1182/bloodadvances.2024015226

@article{189e59ae740045e1b62996f4082bb700,

title = "Atezolizumab Consolidation in Patients with High Risk Diffuse Large B-cell Lymphoma in Complete Remission after R-CHOP",

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.",

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

note = "Copyright {\textcopyright} 2025 American Society of Hematology.",

year = "2025",

month = apr,

day = "18",

doi = "10.1182/bloodadvances.2024015226",

language = "English",

journal = "Blood Advances",

issn = "2473-9529",

publisher = "American Society of Hematology",

}

Nijland, M, Issa, DE, Bult, JAA, Deeren, D, Velders, GA, Nijziel, MR, Sandberg, Y, Vergote, VK, Oosterveld, M, Fijnheer, R, Brouwer, R, Boersma, R, Wu, K, Nieuwenhuizen, L, Vermaat, JS, van Kampen, RJW, Terpstra, WE, Snauwaert, S, van der Poel, MW, de Jongh, E, Durian, M, Strobbe, L, Beeker, A, Gadisseur, AP, Van Rijn, R, Visser, OJ, Doorduijn, J, Snijders, TJF, Silbermann, MH, de Jong, D, Chamuleau, MED, Mous, R, Jalving, M, Visser-Wisselaar, H, Jansen van den Bergh, S, Zwezerijnen, GJ, Bremer, E , Brink, M , Diepstra, A, Chitu, DA, Koene, HR & Zijlstra, JM 2025, 'Atezolizumab Consolidation in Patients with High Risk Diffuse Large B-cell Lymphoma in Complete Remission after R-CHOP', Blood Advances. https://doi.org/10.1182/bloodadvances.2024015226

TY - JOUR

T1 - Atezolizumab Consolidation in Patients with High Risk Diffuse Large B-cell Lymphoma in Complete Remission after R-CHOP

AU - Nijland, Marcel

AU - Issa, Djamila E

AU - Bult, Johanna A A

AU - Deeren, Dries

AU - Velders, Gerjo A

AU - Nijziel, Marten R

AU - Sandberg, Yorick

AU - Vergote, Vibeke Kj

AU - Oosterveld, Margriet

AU - Fijnheer, Rob

AU - Brouwer, Rolf

AU - Boersma, Rinske

AU - Wu, Kalung

AU - Nieuwenhuizen, Laurens

AU - Vermaat, Joost Sp

AU - van Kampen, Roel J W

AU - Terpstra, Wim E

AU - Snauwaert, Sylvia

AU - van der Poel, Marjolein Wm

AU - de Jongh, Eva

AU - Durian, Marc

AU - Strobbe, Leonie

AU - Beeker, Aart

AU - Gadisseur, Alain Pa

AU - Van Rijn, Roos

AU - Visser, Otto J

AU - Doorduijn, Jeanette

AU - Snijders, Tjeerd J F

AU - Silbermann, Matthijs H

AU - de Jong, Daphne

AU - Chamuleau, Martine E D

AU - Mous, Rogier

AU - Jalving, Mathilde

AU - Visser-Wisselaar, Heleen

AU - Jansen van den Bergh, Sonja

AU - Zwezerijnen, Gerben Jc

AU - Bremer, Edwin

AU - Brink, Mirian

AU - Diepstra, Arjan

AU - Chitu, Dana A

AU - Koene, Harry R

AU - Zijlstra, Josée M

PY - 2025/4/18

Y1 - 2025/4/18

N2 - 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.

AB - 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.

U2 - 10.1182/bloodadvances.2024015226

DO - 10.1182/bloodadvances.2024015226

M3 - Article

C2 - 40249860

SN - 2473-9529

JO - Blood Advances

JF - Blood Advances

ER -

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

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