Newly Diagnosed Classical Hodgkin Lymphoma: Optimizing Outcomes in a New Therapeutic Era

The treatment landscape for newly diagnosed classical Hodgkin lymphoma (cHL) has seen remarkable advancements over the past decade, which have been fueled by improved prognostication and response-adapted techniques, and primarily driven by randomized clinical trials, especially via the incorporation of novel targeted therapeutic agents into frontline therapy. 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-stage disease, the completion of PET-based response-adapted 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-acute and long-term consequences. In untreated advanced-stage cHL, the integration of brentuximab vedotin and checkpoint inhibitors has ushered in a new therapeutic era with improved patient outcomes with progressive-free 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-à-vis 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-term quality of life for all individuals with cHL.