Relapsed or refractory classical Hodgkin's lymphoma. Novel therapeutic approaches

Classical Hodgkin's lymphoma is highly curable with risk-adapted first-line therapy. Despite a reduction of potential therapy-associated short-term and long-term toxicities, treatment of patients with relapsed or primary refractory disease (r/r HL) remains a clinical challenge. This review summarizes the currently available data regarding safety and efficacy of different therapeutic approaches in r/r HL and provides recommendations for specific clinical situations. Up to 50% of patients eligible for intensified therapies achieve long-term remission after high-dose chemotherapy and autologous stem cell transplantation (ASCT); however, multiple relapsed, refractory, elderly or frail patients until recently had an unfavorable prognosis with mostly palliative therapy. The anti-CD30 antibody-drug conjugate brentuximab vedotin (BV) constitutes a highly effective and tolerable therapeutic option with some durable complete remissions. Accordingly, BV has been approved for r/r HL after ASCT or two prior therapies. More recently, two checkpoint inhibitors, i.aEuroe., the anti-PD1 antibodies nivolumab and pembrolizumab were also investigated in heavily pretreated r/r HL patients. Both drugs were very well tolerated and resulted in high response rates with long-lasting remission. Nivolumab and pembrolizumab were recently approved for r/r HL after prior treatment with BV. In addition, other targeted drugs, such as AFM13, everolimus, panobinostat, mocetinostat as well as agents, such as lenalidomide or bendamustine showed activity in intensively pretreated r/r HL patients