Current and Future Developments in the Treatment of CD30+ Lymphomas

CD30 is a cell membrane protein expressed on the surface of a range of lymphomas, which has important diagnostic, pathogenic, and prognostic roles. The most common CD30⁺lymphomas are Hodgkin’s lymphoma (HL) and anaplastic large cell lymphoma (ALCL), but other types of lymphoma also express CD30, although less frequently. Attempts to develop a monoclonal antibody therapy that targets CD30 were initially unsuccessful, but recent Phase I and II trials have shown promising results from the use of the immune conjugate brentuximab vedotin in HL and ALCL. Phase III trials are ongoing to evaluate clearly the benefit–risk ratio when compared with standard treatment. The first of these to report preliminary findings, the AETHERA trial, showed improved progression-free survival times in relapsing/refractory HL patients treated with brentuximab vedotin as a consolidation therapy after autologous stem cell transplantation compared with those receiving placebo. Patients with rarer CD30⁺ lymphomas may also benefit from brentuximab vedotin therapy in the future. Moreover, combination treatment with immunomodulatory and cell cycle checkpoint modulators that are currently under development, as well as conventional chemotherapeutic agents, may yield further benefits. To this end, improved methods of CD30 detection and quantitation will improve the delineation of non-HL subtypes in which CD30-targeted therapy may be clinically indicated.