Outcomes of patients with relapsed or refractory classic Hodgkin lymphoma after frontline brentuximab vedotin

Frontline therapy for classic Hodgkin Lymphoma (cHL) incorporating brentuximab vedotin (BV) improves outcomes compared with traditional chemotherapy, but up to 20% of patients relapse and need salvage treatment. Prior retrospective studies examining salvage therapies are mostly limited to patients who received chemotherapy-based treatment in frontline without novel agents. We evaluated outcomes in 116 patients with relapsed/refractory (R/R) cHL who received brentuximab and anthracycline-containing frontline treatment. High risk factors at relapse or progression were common, including primary refractory disease (62%), advanced stage (63%), and extranodal disease (46%). At first salvage, 73% of patients received PD-1 blockade (58% in conjunction with chemotherapy), and 81% received PD-1 blockade at any salvage line. Overall, 78% of patients proceeded to ASCT. With a median follow-up of 19 months, the 2-year PFS and OS from the start of salvage in all patients were 61% and 97% respectively. Among patients with ASCT, the 2-year post-transplant PFS (PFS_HCT) was 76% for patients who had PD-1 blockade as salvage before ASCT, compared with 59% for those who did not. In univariate analysis, PD-1 blockade use in first salvage was significantly associated with improved PFS_HCT, and this association remained statistically significant after adjusting for stage, extranodal involvement, and primary refractory disease (HR 0.31, p = 0.04). Primary refractory disease after BV-AVD emerged as an ongoing unmet need with a significantly inferior 2-year PFS_HCT compared with relapsed patients (58% vs 86%, p = 0.017). Among primary refractory patients who received ASCT, first salvage incorporating a PD-1 blockade showed a trend toward improved PFS_HCT compared with non-PD-1 blockade salvage. These results support PD-1 blockade incorporation as preferred first salvage in R/R cHL after BV-containing frontline therapy.