{"doi":"10.1002/hon.70093_127","title":"127 | HEALTH‐RELATED QUALITY OF LIFE (HRQoL) ENDPOINTS OF THE PHASE III INTERGROUP S1826 ADVANCED‐STAGE, CLASSIC HODGKIN LYMPHOMA (cHL) TRIAL","abstract":"Introduction: Patients with newly diagnosed, advanced stage cHL are at risk for poor HRQoL due to their underlying disease and its treatment. We assessed HRQoL in S1826, a trial showing that nivolumab plus doxorubicin, vinblastine, and dacarbazine (N+AVD) resulted in longer progression-free survival compared to brentuximab vedotin plus AVD (BV+AVD). Methods: S1826 was a phase 3 multicenter trial for patients > 12 years old with stage III or IV newly diagnosed cHL. HRQoL assessment was required for patients able to complete questionnaires in English, Spanish, or French, and was obtained before registration (“baseline”) and at cycle 3, at 4–8 weeks after the end of treatment (EOT), and at 1 and 3 years after randomization using the PROMIS-Fatigue (or Ped PROMIS Fatigue) and the FACT-GOG-Ntx scales. Two primary endpoints for fatigue (at EOT and 1 year) and two for neuropathy (at 1 and 3 years) were pre-specified, each tested using a two-sided alpha = 0.0125 test. We report on mature results through 1 year. Linear regression was used, adjusting for the baseline HRQoL score, age (12–17 vs. 18–60 vs. > 60 years), the international prognostic score (IPS; 0–3 vs. 4–7), and intent to use radiation (yes vs. no). An effect size of 0.3 for both fatigue and neuropathy endpoints was targeted, corresponding to minimal clinically meaningful differences (MCID) of 3.6 points and 3.0 points, respectively. Results: The N = 970 eligible patients were predominantly < 60 years (90.2%) and male (56.1%); 11.8% were Black race, and 32.0% had IPS 4–7. Adherence (i.e., completion rates) was better for the N+AVD arm (Table). For pre-specified primary endpoints, the adjusted PROMIS-Fatigue score was 1.7 (95% CI: −3.1 to −0.4, p = 0.01) points lower (i.e., more fatigue) for the N+AVD arm at EOT, although the difference did not exceed the MCID. At 1 year, there was no significant difference in fatigue (p = 0.83). In contrast, neuropathy scores at 1 year were better for patients on the N+AVD arm, exceeding the MCID (3.0 points, 95% CI: 2.0–3.9, p < 0.001). Secondary findings included significantly worse fatigue at cycle 3, and significantly less neuropathy at cycle 3 and at EOT, for patients on the N+AVD arm (Table); among these, the finding of less neuropathy on the N+AVD arm exceeded the MCID. Conclusions: Despite advanced stage disease and intensive treatment, completion rates of HRQoL assessments were high and did not differ by participant age (data not shown). Worse fatigue was found at the EOT, and less neuropathy throughout year 1, for patients on the N+AVD arm, whereas worse neuropathy was found in the BV-AVD arm at all specified time points. Further analyses are planned to evaluate the effect of these treatments on global HRQoL and further understand the impact of participant age and completion rates/retention on between-arm differences. Research funding declaration: NIH/NCI grant UG1CA189974 Keywords: quality of life, late effects, survivorship care; Hodgkin lymphoma; Hodgkin lymphoma (Pediatric, Adolescent, and Young Adult) Potential sources of conflict of interest: A. F. Herrera Consultant or advisory role: Bristol Myers Squibb; Genentech; Merck; SeaGen; AstraZeneca; Karyopharm; ADC Therapeutics; Takeda; Tubulis; Regeneron; Genmab; Pfizer; Caribou Biosciences; Adicet Bio; Abbvie; Allogene Therapeutics Other remuneration: KiTE; Gilead Sciences K. Davison Consultant or advisory role: BMS, SeaGen S. M. Castellino Consultant or advisory role: SeaGen Inc; Bristol Myers Squibb S. C. Rutherford Consultant or advisory role: ADC Therapeutics, Genmab, Karyopharm, Kite, SeaGen Other remuneration: Genentech, Karyopharm A. M. Evens Consultant or advisory role: Seattle Genetics, Hutchmed, Incyte, Daiichi Sankyo, Epizyme, Novartis, Abbvie, Pharmacyclics K. M. Kelly Consultant or advisory role: Seagen S. K. Parsons Consultant or advisory role: SeaGen","journal":"Hematological Oncology","year":2025,"id":536279,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":1,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.8328,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2025-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":260842,"name":"H. Li","orcid":null,"position":1,"is_corresponding":false},{"id":282395,"name":"Alex F. Herrera","orcid":"0000-0002-9665-7415","position":2,"is_corresponding":false},{"id":559300,"name":"Kelly Davison","orcid":"0000-0001-5159-3916","position":3,"is_corresponding":false},{"id":282785,"name":"Sharon M. Castellino","orcid":"0000-0001-8367-2002","position":4,"is_corresponding":false},{"id":713409,"name":"Hildy Dillon","orcid":null,"position":5,"is_corresponding":false},{"id":1421608,"name":"T. Hernandez","orcid":null,"position":6,"is_corresponding":false},{"id":559298,"name":"Sarah C. Rutherford","orcid":"0000-0002-1064-7727","position":7,"is_corresponding":false},{"id":559297,"name":"Angela Punnett","orcid":"0000-0003-4541-0823","position":8,"is_corresponding":false},{"id":268627,"name":"Michael LeBlanc","orcid":"0000-0001-7192-2860","position":9,"is_corresponding":false},{"id":423661,"name":"Joo Y. Song","orcid":"0000-0003-3497-2513","position":10,"is_corresponding":false},{"id":356246,"name":"Susan M. Smith","orcid":"0000-0001-6027-2727","position":11,"is_corresponding":false},{"id":262607,"name":"Andrew M. Evens","orcid":"0000-0002-6900-1824","position":12,"is_corresponding":false},{"id":321130,"name":"Kara M. Kelly","orcid":"0000-0003-1473-3937","position":13,"is_corresponding":false},{"id":11108,"name":"Jonathan W. Friedberg","orcid":"0000-0002-1420-5563","position":14,"is_corresponding":false},{"id":539568,"name":"Susan K. Parsons","orcid":"0000-0003-0282-6490","position":15,"is_corresponding":false},{"id":1421607,"name":"J. Unger","orcid":null,"position":0,"is_corresponding":true}],"reference_count":0,"raw_metadata":null,"created_at":"2026-07-19T02:52:05.227140Z","pmid":null,"pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}