Balancing risk and benefit in early-stage classical Hodgkin lymphoma

Abstract

With defined chemotherapy and radiotherapy (RT) and risk-adapted treatment, early-stage classical Hodgkin lymphoma (HL) has become curable in a majority of patients. Hence, a major current goal is to reduce treatment-related toxicity while maintaining long-term disease control. Patients with early-stage favorable disease (ie, limited stage without risk factors [RFs]) are frequently treated with 2 cycles of doxorubicin, bleomycin, vinblastine, and dacarbazine (23ABVD) followed by 20-Gy involved-field or involved-site RT (IF/ISRT). In patients with early-stage unfavorable disease (ie, limited stage with RFs), 4 cycles of chemotherapy are usually consolidated with 30-Gy IF/ISRT. Compared with 43ABVD, 2 cycles of bleomycin, etoposide, doxorubicin, cyclo-phosphamide, vincristine, procarbazine, and prednisone (23BEACOPPescalated) followed by 23ABVD improved 5-year progression-free survival (PFS), with similar 5-year overall survival. Recently, treatment strategies based on [18F]fluorodeoxyglucose positron emission tomography (PET) response were evaluated. In early-stage unfavorable HL, a majority of patients achieved a negative interim PET after 23ABVD and an excellent outcome after 43ABVD, whereas in those with a positive interim PET, 23BEACOPPescalated improved 5-year PFS. Furthermore, a PET-guided RT approach was evaluated to decrease long-term toxicity. Although both the RAPID and H10 trials reported poorer disease control without RT, PET-guided omission of RT can constitute a valid therapeutic option in patients with an increased risk of RT-associated toxicity (eg, because of sex, age, or disease localization). Implementation of drugs such as the anti-CD30 antibody-drug conjugate brentuximab vedotin or the anti–programmed death 1 antibodies nivolumab or pembrolizumab might allow further reduction of overall mortality and improve quality of life in affected patients.