Abstract
Introduction While high-dose therapy with autologous stem cell transplantation (HDT/ASCT) following salvage therapy remains the current standard for relapsed/refractory classic Hodgkin lymphoma (RR-cHL), its long-term benefit, particularly in patients who achieve complete remission (CR), is increasingly questioned. Recent phase II trials (Daw et al., 2025a, b; Hoppe et al., 2025) have demonstrated that low-risk pediatric and young adult patients achieving CR with nivolumab-brentuximab vedotin plus radiotherapy, or with conventional regimens, can achieve 5-year event-free survival (EFS) rates exceeding 80% without HDT/ASCT, thereby avoiding the significantly increased late mortality associated with transplantation (Buhtoiarov & Hanna, 2025). Additionally, data from prospective phase II studies presented at ASH 2024 (Abstracts 569 and 4434) further support transplant-free treatment strategies in adult populations. In this context, we compare the long-term outcomes of HDT/ASCT consolidation versus alternative, non-transplant approaches in adult RR-cHL patients who achieve first CR after salvage therapy.
Methods Eligible patients (≥18 years) included those with cHL experiencing relapse or primary refractory disease, defined as disease progression or failure to achieve remission after frontline therapy. Patients who subsequently achieved a complete remission following salvage treatment were included. Participants were stratified into two cohorts: the HDT/ASCT group and the transplant-free group. Progression-free survival (PFS) was defined as the time from the start of salvage therapy to disease progression or death, whichever occurred first. The primary endpoint was 3-year PFS.
Results A total of 163 RR-cHL patients were enrolled. The median age at relapse or progression was 29 years (range 18-76), with 58.9% male. Of these, 116 patients were assigned to the transplant-free group and 47 to the HDT/ASCT group. In the transplant-free group, 60 patients (51.7%) had early-stage disease (I-II), while 56 (48.3%) had advanced-stage disease (III-IV). In the HDT/ASCT group, 12 patients (25.5%) had early-stage disease, and 36 (74.5%) had advanced-stage disease.
The median number of prior therapy lines was 1 (range 1-8) in the HDT/ASCT cohort and 1 (range 1-5) in the transplant-free cohort. About 21.3% (10/47) of patients in the HDT/ASCT group and 12.9% (15/116) in the transplant-free group had received three or more previous lines of therapy. The transplant-free group was subdivided into three salvage treatment arms: checkpoint inhibitors (CPI)-based (n=71), Brentuximab Vedotin (BV)-based (n=16), and chemotherapy alone (n=29). The chemotherapy-alone subgroup included regimens such as GVD (n=12), ABVD (n=8), MOPP (n=3), ICE (n=2), BEACOPP (n=2), among others. Patients in the CPI group received PD-1 antibodies with (n=4) or without (n=8) radiotherapy, PD-1 antibody combined with BV (n=8), or PD-1 antibody combined with chemotherapy with (n=24) or without (n=27) radiotherapy. Thirty-four patients in the CPI group underwent PD-1 maintenance therapy for a median duration of 9 months (range 3-24). The BV group received BV plus chemotherapy, with (n=11) or without (n=5) radiotherapy. In the HDT/ASCT group, salvage therapies included CPI-based (n=16), BV-based (n=1) and chemotherapy-based (n=30) regimens, with 28 patients receiving post-transplant maintenance therapy (PD-1 inhibitors [n=22], thalidomide/lenalidomide [n=5], or BV [n=1]).
With a median follow-up of 3.6 years (IQR, 2.2-5.7) after salvage initiation, 50 patients experienced disease progression: 36 patients (31.0%) in the transplant-free group and 14 patients (29.8%) in the HDT/ASCT group. The 3-year PFS was 68.3% in the transplant-free group and 74.0% in the HDT-ASCT group (HR,1.3; 95% CI, 0.69-2.40; p=0.42), indicating no significant difference between two approaches. Among transplant-free patients, 3-year PFS rates differed by salvage arms: CPI group 71.1% (95% CI, 59.9-84.3), BV group 86.7% (95% CI, 71.1-100.0), and chemotherapy-alone group 53.5% (95% CI 36.3-78.8), with a statistically significant difference across groups (p=0.031).
Conclusions In patients with relapsed/refractory cHL achieving CR after salvage therapy, transplant-free strategies, particularly those based on PD-1 inhibitors and brentuximab vedotin, demonstrate comparable survival outcomes to HDT/ASCT consolidation.
