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

Nijland, M.; Issa, D.E.; Bult, J.A.A.; Deeren, D.; Velders, G.A.; Nijziel, M.R.; Sandberg, Y.; Vergote, V.; Oosterveld, M.; Fijnheer, R.; Brouwer, R.E.; Boersma, R.S.; Wu, K.L.; Nieuwenhuizen, L.; Vermaat, J.S.P.; Kampen, R.J.W. van; Terpstra, W.E.; Snauwaert, S.; Poel, M.W. van der; Jongh, E. de; Durian, M.F.; Strobbe, L.; Beeker, A.; Gadisseur, A.; Rijn, R.S. van; Visser, O.; Doorduijn, J.K.; Snijders, T.J.F.; Silbermann, M.H.; Jong, D. de; Chamuleau, M.; Mous, R.; Jalving, H.; Visser-Wisselaar, H.; Bergh, S.J. van de; Zwezerijnen, G.J.C.; Bremer, E.; Brink, M.; Diepstra, A.; Chitu, D.A.; Koene, H.R.; Zijlstra, J.M.

doi:doi:10.1182/bloodadvances.2024015226

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...Show moreThe 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.Show less

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