High rate of complete responses to immune checkpoint inhibitors in patients with relapsed or refractory Hodgkin lymphoma previously exposed to epigenetic therapy

Lorenzo Falchi,Jennifer E Amengual,Owen A O’Connor,Emily A Lichtenstein,Donald S Colbourn,Ahmed Sawas,Lawrence H Schwartz,Changchun Deng,Karen A Khan

doi:10.1186/s13045-016-0363-1

Abstract

Options for patients with relapsed or refractory (R/R) classical Hodgkin lymphoma (cHL) after brentuximab vedotin (Bv) and autologous stem cell transplantation (ASCT) are limited. Immune checkpoint inhibitors (ICI) are active in this population but rarely induce complete response (CR). Ten patients with R/R cHL after ASCT and Bv received pembrolizumab (n = 8) or nivolumab (n = 2). Five had been previously exposed to 5-azacitidine on a phase 1 study. Among nine evaluable patients, seven (78%) achieved CR, one partial response, and one reduction of tumor burden. All five patients who had received 5-azacitidine prior to ICI achieved CR, while only two of four who did not receive prior 5-azacitidine achieved CR. At a median follow-up of 9.9 months [0.5–14.3], eight patients are alive and five are still receiving treatment. We documented an unprecedented CR rate after ICI in patients with R/R cHL. We hypothesize that hypomethylating agents might have an immune priming effect and enhance the efficacy of ICI.Electronic supplementary materialThe online version of this article (doi:10.1186/s13045-016-0363-1) contains supplementary material, which is available to authorized users.

Highlights

Options for patients with relapsed or refractory (R/R) classical Hodgkin lymphoma after brentuximab vedotin (Bv) and autologous stem cell transplantation (ASCT) are limited
* Correspondence: oo2130@cumc.columbia.edu 1Center for Lymphoid Malignancies, Division of Hematology/Oncology, Department of Medicine, Columbia University Medical Center, 51 West 51st Street, Suite 200, New York, NY 10019, USA Full list of author information is available at the end of the article antibodies nivolumab and pembrolizumab, two immune checkpoint inhibitors (ICI), are highly active in patients with relapsed or refractory (R/R) classical Hodgkin lymphoma (cHL) but induced complete response (CR) only in a minority of them [5, 6]
We report our experience with Immune checkpoint inhibitors (ICI) in ten patients with R/R cHL, five of whom were previously exposed to 5-azacitidine

Summary

Introduction

Options for patients with relapsed or refractory (R/R) classical Hodgkin lymphoma (cHL) after brentuximab vedotin (Bv) and autologous stem cell transplantation (ASCT) are limited. * Correspondence: oo2130@cumc.columbia.edu 1Center for Lymphoid Malignancies, Division of Hematology/Oncology, Department of Medicine, Columbia University Medical Center, 51 West 51st Street, Suite 200, New York, NY 10019, USA Full list of author information is available at the end of the article antibodies nivolumab and pembrolizumab, two immune checkpoint inhibitors (ICI), are highly active in patients with relapsed or refractory (R/R) cHL but induced complete response (CR) only in a minority of them [5, 6]. The hypomethylating agent (HMA) 5-azacitidine was shown to induce expression of retroviral genes in tumor cells and trigger a T cell-mediated response, potentially synergizing with ICI [7].

Results

Conclusion