Nivolumab consolidation in patients with double and triple hit high-grade B-cell lymphoma in complete metabolic remission after DA-EPOCH-R

Patients with high-grade B-cell lymphoma harboring MYC , BCL2 , and/or BCL6 rearrangements (HGBL-DH/TH) frequently relapse after induction chemoimmunotherapy. High MYC is claimed to contribute to immune escape. We evaluated consolidation with PD-1 blockade in patients with HGBL-DH/TH in complete metabolic remission (CMR) after DA-EPOCH-R. In this prospective, multicenter, single-arm, phase II trial (NCT03620578), patients ≥18 years with newly diagnosed, stage II–IV HGBL-DH/TH in CMR received nivolumab 480 mg intravenously every 4 weeks for 1 year. The primary endpoint was disease-free survival (DFS) from nivolumab initiation. Between August 2018 and March 2022, 97 patients were enrolled. One patient was excluded for CNS involvement. After DA-EPOCH-R induction, 63/96 (66%) patients achieved CMR and received nivolumab. With a median follow-up of 3.2 years (IQR: 2.8–3.9) from nivolumab initiation, 1- and 2-year DFS were 92% (95% CI: 86–99%) and 89% (95% CI: 81–97%). One- and 2-year overall survival (OS) were 97% (95% CI: 93–100%) and 95% (95% CI: 90–100%). During nivolumab, grade 3–4 adverse events occurred in 13/63 (21%) patients, including 5 infections. Fourteen immune-related AEs occurred in 13/63 (21%) patients (5% grade 3, 16% grade 2). In conclusion, nivolumab consolidation for HGBL-DH/TH patients in CMR after DA-EPOCH-R is feasible and results in high DFS and OS. Clinical trial registration : this trial was registered at www.clinicaltrials.gov as #NCT03620578 and in the EudraCT database as 2017-003631-12.