BACKGROUND: The prognosis of early unfavorable and advanced stage classic Hodgkin lymphoma (cHL) remains suboptimal with the widely used ABVD (doxorubicin, bleomycin, vinblastine, and dacarbazine) regimen. Novel agents such as brentuximab vedotin (BV) and anti-PD-1 antibody have demonstrated high efficacy and good tolerance in relapsed/refractory cHL and have also shown promising results in the frontline setting. However, concurrent administration of anti-PD-1 antibody plus AVD in comparison with traditional ABVD regimen alone in untreated classic Hodgkin lymphoma (cHL) has yet to be adequately studied in real-world clinical practice. METHODS: We enrolled eligible adult patients with histologically confirmed cHL who had received initial treatment with the ABVD regimen, or the novel combination regimens of anti-PD1-AVD. The study endpoints included modified progression-free survival (mPFS) and complete response (CR) after 2 cycles of therapy. Propensity score matching (PSM) was performed to balance clinical variables between regimens prior to efficacy comparisons. RESULTS: Of 172 patients, 137 received the ABVD regimen and 35 received the anti-PD1-AVD regimen. With a median follow-up of 37.7 months, significantly prolonged 3-year modified PFS was reported for anti-PD1-AVD versus ABVD (PSM: 91.0 vs. 61.6%, p = 0.032). Significantly improved CR rate was observed with anti-PD1-AVD versus ABVD (PSM: 86.7 vs. 63.8%, p = 0.049). CONCLUSIONS: In this real-world study, concurrent anti-PD1 antibody with AVD showed significantly prolonged modified PFS and improved CR rate after cycle 2 versus ABVD regimen, supporting the use of novel agents in frontline therapy.