Classical Hodgkin Lymphoma Today

Classical Hodgkin Lymphoma is one of the most curable neoplasms worldwide, particularly among young adults. Significant advances have been made to maximize treatment efficacy and minimize acute and long-term toxicities, including infertility, cardiovascular complications and secondary primary malignancies. Pretreatment prognostic stratification and interim PET response are the cornerstones of personalized treatment strategies. Circulating tumor cell-free DNA represents an investigational tool for genotyping Hodgkin Lymphoma at diagnosis and monitoring treatment response. An abbreviated course of polychemotherapy followed by involved-site/involved nodal radiotherapy continues to be the gold standard in early-stage diseases, while polychemotherapy remains the mainstay for the treatment of advanced-stage disease with or without the incorporation of novel agents, such as the anti-CD30 antibody-drug conjugate brentuximab-vedotin (BV) or the anti-PD1 checkpoint inhibitors (CPI) nivolumab and pembrolizumab. In elderly patients, treatment requires careful adaptation to minimize acute toxicities, often reducing the chemotherapy load or incorporating new targeted therapies. Although consolidation with autologous stem cell transplantation (ASCT) after salvage chemotherapy remains the standard approach in patients with chemosensitive relapsed/refractory cHL, significant improvements in response rate and duration have been achieved when BV and CPI are integrated into salvage regimens prior to ASCT or as post-transplant maintenance. Both classes of drugs are also approved as monotherapy in patients who are transplant-ineligible or have refractory/relapsed disease. Novel therapeutic approaches, including anti-CD30 CAR-T cells and the combination of the anti-CD30/CD16A bispecific antibody AFM13 with preactivated allogeneic cord blood-derived NK cells, are under investigation for patients who have failed the currently approved treatment options.