Efficacy and Safety of Novel-Agent-Based Front-Line Therapy in Older Adults Aged ≥ 60 Years With Classic Hodgkin Lymphoma: A Systematic Review and Meta-Analysis.

Older patients with classical Hodgkin lymphoma (cHL) have poorer outcomes than younger patients, largely due to comorbidities, reduced chemotherapy tolerance, and limited representation in clinical trials. Brentuximab Vedotin (BV) and PD-1 inhibitors have entered frontline use in this population, but the optimal approach remains uncertain. We performed a systematic review and pooled analysis to evaluate the efficacy and safety of frontline regimens in patients aged ≥ 60 years with cHL. Studies reporting complete response (CR), overall response rate (ORR), progression-free survival (PFS), and toxicity were included. Outcomes were pooled using random-effects models. A total of 11 studies including 568 patients were analyzed. The pooled CR rate was 71% (95% CI: 57-81) and pooled 2-year PFS was 66% (95% CI: 45-83), with significant heterogeneity. Nivolumab-based regimens appeared, in indirect subgroup comparisons with marked heterogeneity, to have a higher pooled response rates and PFS than BV-based regimens, and were associated with lower rates of treatment discontinuation, Grade ≥ 3 infections, and neuropathy. Novel agent-based regimens produced better efficacy and lower toxicity than traditional chemotherapy in newly diagnosed older adults with cHL. Among novel agents, nivolumab-based regimens had more favorable efficacy and tolerability than BV-based regimens, though these comparisons are indirect and may reflect differences in study design and patient selection.