Novel treatment concepts in Hodgkin lymphoma

Treatment of classical Hodgkin's lymphoma (HL) has been a success story, with cure of localized disease with radiotherapy in the 1930s, cure of advanced stages with combination chemotherapy with/without radiotherapy in the mid-1960s and continuous improvements since then. Nonetheless, at present approximately 2% of patients with classical HL are primarily refractory to conventional therapy with only 50% becoming long-term survivors. Another 13% of patients relapse, with only 60% being alive 10 years postrecurrence (as exemplified in this review in a Swedish cohort of 18- to 65-year-old patients diagnosed during the period 1992-2009). Recently, novel targeted drugs were approved for refractory/relapsed HL and here we review results of trials that form the basis for these approvals as well as new trials. In summary, brentuximab vedotin can be used in refractory patients (i) as a complement to high-dose chemotherapy with autologous stem cell transplantation (SCT) improving the chances of being able to proceed to an allogenic SCT and cure, (ii) as consolidation after autologous SCT and (iii) as palliative life-prolonging treatment. However, we have yet to determine whether this drug provides the greatest benefit in first- or second-line treatment, as consolidation or in refractory disease or relapse. Trials of immune checkpoint inhibitors, such as those targeting programmed death 1 (nivolumab and pembrolizumab), and thus not primarily the tumour cells, have shown overall response rates of >65%. Long-term results and data from Phase III trials are still lacking, but nivolumab recently gained approval in refractory patients already treated with brentuximab vedotin and autologous SCT. Other novel treatments of interest include T cells with a chimeric antigen receptor and combination therapies with histone deacetylase inhibitors.