Bendamustine, gemcitabine, and vinorelbine (BeGEV) regimen followed by ASCT Induces Durable Remissions in PD-(L)1 inhibitor-resistant Refractory/relapsed classical Hodgkin lymphoma: A single-center, long-term study

Abstract 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.