Background Primary refractory or relapsed disease occurs in 20–40% of classical Hodgkin lymphoma (cHL) patients after first-line therapy. Although PD-(L)1 inhibitors are standard salvage therapy for refractory/relapsed (r/r) cHL, acquired resistance is increasingly prevalent. Post-PD-(L)1 inhibitor failure options remain limited, with brentuximab vedotin (BV) constrained by cost barriers in resource-limited settings. Autologous stem cell transplantation (ASCT) offers curative potential but requires salvage-sensitive regimen (≥partial response, PR) pre-transplantation. Thus, developing an effective, low-toxicity, and cost-efficient re-induction regimen for PD-(L)1 inhibitor-resistant r/r cHL is an urgent unmet need.

Aim To assess the efficacy, safety, and survival outcomes of the bendamustine, gemcitabine, and vinorelbine (BeGEV) regimen followed by ASCT in patients with PD-(L)1 inhibitor-resistant r/r cHL. Additionally, the impact of bendamustine on hematopoietic stem cell mobilization was investigated.

Methods This retrospective analysis enrolled eight patients with r/r cHL treated at Henan Cancer Hospital between May 2021 and May 2023. All participants had PD-(L)1 inhibitor-refractory/relapsed or intolerant disease, received four 21-day cycles of BeGEV re-induction therapy: bendamustine (90 mg/m² IV on days 2–3), gemcitabine (800 mg/m² IV on days 1 and 4), and vinorelbine (1.5 mg/m² [max 2 mg] IV on day 1). Patients achieving ≥ PR underwent immediate ASCT with G-CSF-only mobilization and BEAM conditioning (BCNU 300 mg/m² day -7, etoposide 200 mg/m² days -6 to -3, cytarabine 200 mg/m² days -6 to -3, melphalan 140 mg/m² day -2). Post-ASCT surveillance included quarterly clinical/radiologic assessments in year 1 and semi-annually thereafter, without maintenance therapy.

Results Eight patients were enrolled and median age was 36 years (range: 28-52). All presented with advanced-stage (Ann Arbor III–IV) and a median of 4 prior therapy lines before PD-(L)1 inhibitor. After four cycles of BeGEV chemotherapy, the overall response rate (ORR) was 100% (8/8), with a complete response (CR) rate of 62.5% (5/8). All patients underwent subsequent ASCT, achieving a post-ASCT ORR of 100% (8/8) and an improved CR rate of 87.5% (7/8). The most frequent BeGEV-related adverse event was grade 1–2 neutropenia (occurring in 2/8 patients, 25.0%). No bendamustine-related toxicities such as alopecia or peripheral neuropathy were observed.

With a median follow-up of 32 months, neither median progression-free survival (PFS) nor overall survival (OS) had been reached. Six patients (75.0%, 6/8) maintained continuous CR, while one patient (12.5%, 1/8) sustained PR. Only one patient (12.5%, 1/8) experienced disease progression at 17 months post-ASCT; notably, this patient had achieved PR after BeGEV and CR post-ASCT. One patient achieved the longest follow-up duration of 50 months and remained disease-free.

All eight patients achieved successful mobilization of peripheral blood stem cells, with a mean CD34+ cell yield of 9.04 × 10⁶/kg. Following ASCT, rapid hematopoietic recovery was observed, with median times to neutrophil engraftment and platelet engraftment of 11 days and 15 days, respectively.

Remarkably, total treatment costs were contained at <100,000 CNY (~14,000 USD) per patient, enabled by reimbursement-eligible BeGEV agents under China's healthcare policy and avoidance of post-ASCT maintenance therapy.

Conclusion Despite the limited sample size, this long-term study demonstrates that BeGEV-ASCT induces durable remissions in PD-(L)1 inhibitor-resistant cHL with favorable cost profiles, positioning it as a viable therapeutic strategy for resource-limited settings. Prospective multi-center validation is warranted.

This content is only available as a PDF.
2025
Sign in via your Institution