In a prospective, multicenter single-arm Phase 2 study in China, orelabrutinib plus R-CDOP produced a 70.5% objective response rate at the end of induction among 44 previously untreated diffuse large B-cell lymphoma patients with high CNS relapse risk. The study outcome is framed as an early efficacy signal in a difficult-to-treat subgroup where CNS involvement drives treatment escalation. Because it is single-arm, the work primarily supports signal generation rather than definitive comparative benefit. The key clinical next steps are confirmation through controlled trials and further characterization of durability, safety, and CNS-specific outcomes. For oncology development teams, the readout strengthens confidence in BTK-inhibition plus immunochemotherapy combinations in high-risk settings, but investigators will need follow-up to establish long-term control.