Improving salvage regimens prior to autologous stem cell transplantation in relapsed/refractory Hodgkin’s lymphoma patients: updates in the novel therapy era

INTRODUCTION: Relapsed or refractory (R/R) classical Hodgkin lymphoma (cHL) has historically been managed with multi-agent salvage chemotherapy followed by autologous stem cell transplantation (ASCT). Recently, brentuximab vedotin (BV) and programmed cell death protein 1 (PD-1) inhibitors in the salvage setting have substantially improved response rates and post-transplant outcomes. A PubMed search was conducted to identify key studies evaluating salvage therapies in R/R transplant-eligible cHL. AREAS COVERED: This review summarizes conventional salvage regimens and modern BV/ PD-1 inhibitor-based strategies, including response-adapted approaches. Emerging data on chemotherapy-sparing regimens, retreatment after frontline PD-1 inhibitor exposure, and novel consolidation strategies are discussed. The evolving role of post-ASCT maintenance, circulating tumor DNA-guided response assessment, potential for ASCT omission in deep molecular remission, and the next generation of immunotherapeutic approaches for multiply relapsed disease are also reviewed. EXPERT OPINION: PD-1 inhibitor-based salvage regimens now represent the preferred strategy for many transplant-eligible patients, producing unprecedented complete response rates and durable disease control after ASCT. The next major advance will be biologically guided risk stratification using metabolic and molecular response measures to individualize consolidation and potentially omit ASCT in selected patients. Novel immune-based therapies are urgently needed for patients who relapse after BV and PD-1 inhibitor therapy.