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 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.