Hodgkin’s Lymphoma- a Review: Future Directions in the Era of Targeted Therapy

Abstract

Hodgkin lymphoma (HL) is a unique hematopoietic neoplasm characterized by cancerous Reed-Sternberg cells in an inflammatory background. Patients are commonly diagnosed in their 20s with a small proportion of patients in their 70s. Patients usually present with supra-diaphragmatic lymphadenopathy with or without associated systemic B symptoms. Even in advanced disease, HL is highly curable with combination chemotherapy, or combined-modality treatment. Although the same doxorubicin, bleomycin, vinblastine, and dacarbazine (ABVD) chemotherapeutic regimen has been the mainstay of therapy over the last 30 years, risk-adapted approaches have helped de-escalate therapy in low-risk patients while intensifying treatment for higher risk patients. Limited stage disease without risk factors (RFs), are frequently treated with two cycles of doxorubicin, bleomycin, vinblastine and dacarbazine (ABVD) followed by 20Gy involved-field or -site radiotherapy (IF/IS-RT). In patients with early-stage unfavorable disease, four cycles of chemotherapy are usually consolidated with 30Gy IF/IS-RT. Compared to 4xABVD, 2 cycles of escalated BEACOPP followed by 2 cycles of ABVD ("2+2") improved 5-year progression-free survival with similar 5-year overall survival. Recently, treatment strategies based on 18FDG positron emission tomography response were evaluated. PET-guided omission of RT can constitute a valid therapeutic option in patients with an increased risk of RT-associated toxicity. There are an increasing number of salvage therapies available to patients who are not cured with initial therapy. These include alternative chemotherapy combinations, the novel antibody-drug conjugate brentuximab, or high-dose autologous or allogeneic hematopoietic stem cell transplantation. The programmed death-1 inhibitors nivolumab and pembrolizumab have both demonstrated high response rates and durable remissions in patients with relapsed/refractory HL.