Classic Hodgkin Lymphoma

Importance: Hodgkin lymphoma (HL) is a lymphoid malignancy derived from B cells. Globally, there were 82 409 new cases of HL in 2022, associated with 22 701 deaths. In the US, 8720 incident cases of HL and 1150 deaths due to HL were reported in 2025. Classic HL (cHL) accounts for 90% to 95% of HL cases. Observations: Classic HL has a bimodal age distribution, with an initial peak at age 15 to 35 years and a second, smaller peak at approximately age 70 years. The median age at cHL diagnosis is 33 years. Most patients present with supradiaphragmatic lymphadenopathy (cervical, mediastinal, supraclavicular, or axillary lymph node involvement or a combination of these lymph nodes); isolated infradiaphragmatic involvement occurs in less than 10% of individuals. Approximately 30% to 40% of patients have B (systemic) symptoms, including fevers (>38.3 °C), drenching sweats, and unintentional weight loss (>10% of body weight during the prior 6 months). Risk factors for cHL include Epstein-Barr virus infection, immune dysregulation (autoimmunity or immunosuppression), and familial predisposition. Patients with early-stage cHL (stage I-II) are risk stratified based on presence of favorable or unfavorable features, which include older age, elevated erythrocyte sedimentation rate, B symptoms, higher disease bulk (>10 cm for a nodal mass or greater than one-third of the internal transverse thoracic diameter at T5 to T6 for a mediastinal mass, measured on chest radiograph), increased number of nodal sites, and extranodal involvement. Patients with early-stage cHL receive chemotherapy with or without consolidative radiotherapy; advanced-stage disease (stage III-IV) is typically treated with chemotherapy alone. Novel agents, including anti-programmed cell death 1 immunotherapy or the CD30-targeted antibody-drug conjugate brentuximab vedotin, are combined with chemotherapy for some patients with early-stage unfavorable cHL and all patients with advanced-stage cHL. Patients with relapsed or refractory cHL who meet eligibility criteria should undergo high-dose chemotherapy and autologous stem cell transplant, with curative intent. Allogeneic stem cell transplant is reserved for select patients with relapse after high-dose chemotherapy and autologous stem cell transplant. Cure is achieved in up to 90% of treated patients with both early-stage and advanced-stage disease. However, survivors have increased risk of secondary malignancies (including non-Hodgkin lymphomas; breast, lung, and colorectal cancers; and myelodysplasia), cardiopulmonary dysfunction, and thyroid dysfunction. Conclusions and Relevance: First-line treatment for cHL is chemotherapy, with addition of radiotherapy for some patients with early-stage disease. Select patients with unfavorable early-stage cHL and all patients with advanced-stage cHL should also receive anti-programmed cell death 1 immunotherapy or a CD30-targeted antibody-drug conjugate in addition to chemotherapy. Patients with relapsed or refractory cHL should be evaluated for stem cell transplant.