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The studies include several recent landmark clinical trials that integrated novel targeted therapeutic agents into frontline therapy for adolescents and adults with cHL. For early\u2010stage disease, the completion of PET\u2010based response\u2010adapted studies has resulted in refined therapeutic approaches, particularly informing the amount and type of chemotherapy as well as the impact of radiotherapy, balancing immediate efficacy with the mitigation of post\u2010acute and long\u2010term consequences. In untreated advanced\u2010stage cHL, the integration of brentuximab vedotin and checkpoint inhibitors has ushered in a new therapeutic era with improved patient outcomes with progressive\u2010free survival rates exceeding 90%. In addition, outcomes have significantly improved for older cHL patients, partly due to the understanding of the unique needs of this patient population (e.g., the impact of geriatric assessments) and vis\u2010\u00e0\u2010vis frontline regimens that have incorporated targeted therapeutic agents. Future directions in cHL emphasize the need for prospective clinical trials that include dynamic clinical prediction models, metabolic tumor burden, ctDNA, and other critical biomarkers to establish predictive factors of treatment effect that yield individualized therapeutic options for patients. Continued innovations in frontline therapy, coupled with efforts to address unmet needs in specific populations, promise to enhance survival rates further and preserve long\u2010term quality of life for all individuals with cHL.<\/jats:p>","DOI":"10.1002\/hon.70066","type":"journal-article","created":{"date-parts":[[2025,6,15]],"date-time":"2025-06-15T17:51:55Z","timestamp":1750009915000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Newly Diagnosed Classical Hodgkin Lymphoma: Optimizing Outcomes in a New Therapeutic Era"],"prefix":"10.1002","volume":"43","author":[{"given":"Andrew M.","family":"Evens","sequence":"first","affiliation":[{"name":"Division of Blood Disorders Rutgers Cancer Institute Rutgers Robert Wood Johnson Medical School  New Brunswick New Jersey USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2025,6,15]]},"reference":[{"key":"e_1_2_9_2_1","doi-asserted-by":"publisher","DOI":"10.1200\/jco.2001.19.11.2905"},{"key":"e_1_2_9_3_1","doi-asserted-by":"publisher","DOI":"10.1200\/jco.2003.03.023"},{"key":"e_1_2_9_4_1","doi-asserted-by":"publisher","DOI":"10.1200\/jco.2005.05.2746"},{"key":"e_1_2_9_5_1","doi-asserted-by":"publisher","DOI":"10.1136\/bmj.g7594"},{"key":"e_1_2_9_6_1","first-page":"P053","volume-title":"13th International Symposium on Hodgkin Lymphoma (ISHL), Cologne, Germany, HemaSphere","author":"Rodday A. 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