Evolution of therapeutic paradigms in Hodgkin lymphoma: from "cure-oriented" to "functional cure".

Hodgkin lymphoma (HL) is a B-cell-derived hematologic malignancy originating from germinal centre B cells. Owing to its remarkable sensitivity to chemotherapy and radiotherapy, HL has become one of the most curable adult malignancies. Over the past decades, treatment regimens such as ABVD and escalated BEACOPP, combined with radiotherapy, have achieved 5-year survival rates exceeding 90% in early-stage patients and long-term remission rates above 75% in advanced-stage disease. However, long-term toxicities associated with conventional therapies-including secondary malignancies, cardiovascular disease, pulmonary fibrosis, and infertility-have increasingly compromised survivors' quality of life. Meanwhile, approximately 5%-10% of patients exhibit primary refractory disease, and 10%-30% eventually relapse.In recent years, the emergence of targeted and immunotherapeutic agents, particularly the anti-CD30 antibody-drug conjugate (brentuximab vedotin) and immune checkpoint inhibitors (e.g., PD-1 inhibitors), has profoundly reshaped the therapeutic landscape of HL. This review systematically summarises the epidemiological characteristics and biological foundations of HL, as well as the achievements and limitations of conventional therapies. We place particular emphasis on key clinical trial evidence in recent years and discuss paradigm shifts in four major areas: treatment de-escalation and toxicity reduction in frontline therapy, precision salvage strategies for relapsed/refractory HL, the evolving role of transplantation, and the application of precision medicine tools such as circulating tumour DNA (ctDNA) and molecular subtyping. We further explore how HL treatment is transitioning from a "cure-oriented" model focused solely on survival to a novel paradigm of "functional cure" that balances efficacy with long-term quality of life. We define "functional cure" as durable remission with minimal long-term toxicity, preserving organ function and quality of life-a unifying principle of modern HL management. Special attention is given to clinical decision-making in PD-1-exposed patients, emerging therapeutic targets, cellular therapies, and the growing role of real-world evidence. These insights aim to inform future individualised treatment strategies in HL.