title: High rate of complete responses to immune checkpoint inhibitors in patients with relapsed or refractory Hodgkin lymphoma previously exposed to epigenetic therapy.
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.
authors.affiliation: Center 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.
authors.forename: Lorenzo
authors.initials: L
authors.lastname: Falchi
authors.affiliation: Center 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.
authors.forename: Ahmed
authors.initials: A
authors.lastname: Sawas
authors.affiliation: Center 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.
authors.forename: Changchun
authors.initials: C
authors.lastname: Deng
authors.affiliation: Center 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.
authors.forename: Jennifer E
authors.initials: JE
authors.lastname: Amengual
authors.affiliation: Center 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.
authors.forename: Donald S
authors.initials: DS
authors.lastname: Colbourn
authors.affiliation: Center 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.
authors.forename: Emily A
authors.initials: EA
authors.lastname: Lichtenstein
authors.affiliation: Center 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.
authors.forename: Karen A
authors.initials: KA
authors.lastname: Khan
authors.affiliation: Department of Radiology, Columbia University Medical Center, 180 Fort Washington Avenue, New York, NY, 10032, USA.
authors.forename: Lawrence H
authors.initials: LH
authors.lastname: Schwartz
authors.affiliation: Center 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. oo2130@cumc.columbia.edu.
authors.forename: Owen A
authors.initials: OA
authors.lastname: O'Connor
mesh_terms: D000911:Antibodies, Monoclonal / Q000494:pharmacology / Q000627:therapeutic use; D061067:Antibodies, Monoclonal, Humanized / Q000494:pharmacology / Q000627:therapeutic use; D000964:Antimetabolites, Antineoplastic / Q000494:pharmacology; D000074322:Antineoplastic Agents, Immunological / Q000494:pharmacology / Q000627:therapeutic use*; D001374:Azacitidine / Q000494:pharmacology; D059447:Cell Cycle Checkpoints / Q000187:drug effects; D019175:DNA Methylation / Q000187:drug effects; D006689:Hodgkin Disease / Q000188:drug therapy*; D006801:Humans; D000077594:Nivolumab; D012074:Remission Induction / Q000379:methods; D016879:Salvage Therapy / Q000379:methods*
chemical_list: D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D000964:Antimetabolites, Antineoplastic; D000074322:Antineoplastic Agents, Immunological; D000077594:Nivolumab; C582435:pembrolizumab; D001374:Azacitidine
keywords: Azacitidine; Epigenetic therapy; Hodgkin lymphoma; Nivolumab; Pembrolizumab