PD-1 inhibitors in patients with Hodgkin lymphoma

Most patients with Hodgkin lymphoma (HL) are cured with chemotherapy alone or combined with radiotherapy. However, 15–20% of patients have refractory disease or relapse (RR) after the primary treatment, and the prognosis of those who do not respond to salvage therapy is poor. Several novel targeted approaches to treating relapsed/refractory HL have significantly improved survival of these patients in recent years. Nivolumab and pembrolizumab were the first-in-class inhibitors of the programmed death-1 (PD-1) receptor, impairing the interaction between PD-1 and its ligands, PD-L1 and PD-L2. In HL, these checkpoint inhibitors (CPI) suppress the T-cell tolerance induced by the strong expression of PD1 ligands in tumour cells, which is related to PD-L1 gene alterations in 9p24.1 observed in most patients [ [1] Roemer M.G.M. Advani R.H. Ligon A.H. Natkunam Y. Redd R.A. Homer H. et al. PD-L1 and PD-L2 genetic alterations define classical Hodgkin lymphoma and predict outcome. J Clin Oncol Off J Am Soc Clin Oncol. 2016; 34 (10): 2690-2697 Google Scholar ]. Approval of these drugs in 2016 and 2017 resulted in high overall response rates (ORRs) and a favourable safety profile among heavily pretreated patients in phase II2 studies [ [2] Chen R. Zinzani P.L. Fanale M.A. Armand P. Johnson N.A. Brice P. et al. Phase II study of the efficacy and safety of pembrolizumab for relapsed/refractory classic Hodgkin lymphoma. J Clin Oncol. 1 juill 2017; 35: 2125-2132 Google Scholar , [3] Younes A. Santoro A. Shipp M. Zinzani P.L. Timmerman J.M. Ansell S. et al. Nivolumab for classical Hodgkin's lymphoma after failure of both autologous stem-cell transplantation and brentuximab vedotin: a multicentre, multicohort, single-arm phase 2 trial. Lancet Oncol. Sept 2016; 17: 1283-1294 Google Scholar ]. The significant clinical benefit has therefore led to improvements in the outcomes of patients with RR HL after brentuximab vedotin (BV) and/or autologous transplant (autologous stem cell transplantation [autoSCT]) failure, allowing a bridge to transplant in some of them. Currently, the US Food and Drug Administration (FDA) and European Medicines Agency (EMA) have approved nivolumab for adult patients with RR-HL after failure of both autoSCT and BV. The EMA has also approved pembrolizumab for adult patients with RR-HL who failed both autoSCT and BV or at least two chemotherapy regimens and BV if they are ineligible for autoSCT, and the FDA has approved it for refractory HL or patients who have relapsed after three prior lines of therapy [ [4] Vassilakopoulos T.P. Chatzidimitriou C. Asimakopoulos J.V. Arapaki M. Tzoras E. Angelopoulou M.K. et al. Immunotherapy in Hodgkin lymphoma: present status and future strategies. Cancers. 29 juill 2019; 11: 1071 Google Scholar ].