{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,25]],"date-time":"2026-08-25T19:41:27Z","timestamp":1787686887692,"version":"build-2784847793"},"reference-count":154,"publisher":"MDPI AG","issue":"18","license":[{"start":{"date-parts":[[2023,9,11]],"date-time":"2023-09-11T00:00:00Z","timestamp":1694390400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cancers"],"abstract":"<jats:p>Most patients with classic Hodgkin lymphoma (cHL) are cured with combination chemotherapy, but approximately 10\u201320% will relapse, and another 5\u201310% will have primary refractory disease. The treatment landscape of relapsed\/refractory (R\/R) cHL has evolved significantly over the past decade following the approval of brentuximab vedotin (BV), an anti-CD30 antibody-drug conjugate, and the PD-1 inhibitors nivolumab and pembrolizumab. These agents have significantly expanded options for salvage therapy prior to autologous hematopoietic cell transplantation (AHCT), post-transplant maintenance, and treatment of relapse after AHCT, which have led to improved survival in the modern era. In this review, we highlight our approach to the management of R\/R cHL in 2023 with a focus on choosing first salvage therapy, post-transplant maintenance, and treatment of relapse after AHCT. We also discuss the management of older adults and transplant-ineligible patients, who require a separate approach. Finally, we review novel immunotherapy approaches in clinical trials, including combinations of PD-1 inhibitors with other immune-activating agents as well as novel antibody-drug conjugates, bispecific antibodies, and cellular immunotherapies. Ongoing studies assessing biomarkers of response to immunotherapy and dynamic biomarkers such as circulating tumor DNA may further inform treatment decisions and enable a more personalized approach in the future.<\/jats:p>","DOI":"10.3390\/cancers15184509","type":"journal-article","created":{"date-parts":[[2023,9,11]],"date-time":"2023-09-11T09:11:18Z","timestamp":1694423478000},"page":"4509","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":25,"title":["Optimizing Treatment for Relapsed\/Refractory Classic Hodgkin Lymphoma in the Era of Immunotherapy"],"prefix":"10.3390","volume":"15","author":[{"given":"Michael P.","family":"Randall","sequence":"first","affiliation":[{"name":"Division of Hematology\/Oncology, Department of Medicine, University of California San Francisco, San Francisco, CA 94143, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael A.","family":"Spinner","sequence":"additional","affiliation":[{"name":"Division of Hematology\/Oncology, Department of Medicine, University of California San Francisco, San Francisco, CA 94143, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2023,9,11]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1999","DOI":"10.1200\/JCO.2016.70.9410","article-title":"Long-Term Follow-Up of Contemporary Treatment in Early-Stage Hodgkin Lymphoma: Updated Analyses of the German Hodgkin Study Group HD7, HD8, HD10, and HD11 Trials","volume":"35","author":"Sasse","year":"2017","journal-title":"J. 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