Advances in CD30- and PD-1-targeted therapies for classical Hodgkin lymphoma

Abstract

CD30 and programmed cell death protein 1 (PD-1) are two ideal therapeutic targets in classical Hodgkin lymphoma (cHL). The CD30 antibody-drug conjugate (ADC) brentuximab vedotin and the PD-1 antibodies nivolumab and pembrolizumab are highly efficacious in treating relapsed and/or refractory cHL. Ongoing studies are evaluating their efficacy in earlier lines of therapy and have demonstrated encouraging results. These agents are expected to further change the landscape of cHL management. Increased cure rates and reduced long-term toxicity from traditional chemotherapy and radiotherapy are likely with the emergence of these novel targeted therapies.

Fig. 1

Mechanisms of action of brentuximab vedotin and anti-PD-1 antibodies. Brentuximab vedotin binds to CD30 on the HRS cell surface and gets internalized into the cell via endocytosis. The cytotoxic MMAE then gets cleaved from the anti-CD30 antibody and interrupts mitosis. The anti-PD-1 antibodies nivolumab and pembrolizumab bind to PD-1 on T cells and block the PD-L1/PD-1-mediated immune checkpoint signaling, allowing reactivation of T cells that exert cytotoxic function against HRS cells. HRS, Hodgkin and Reed-Sternberg; MMAE, monomethyl auristatin E; MHC I, major histocompatibility complex (MHC) type I; TCR, T cell receptor