{"doi":"10.1002/hon.70093_20","title":"20 | IMPACT OF EBV STATUS AND HISTOLOGY ON OUTCOMES WITH NIVOLUMAB‐AVD VERSUS Bv‐AVD IN PATIENTS ENROLLED ON SWOG S1826","abstract":"Introduction: Historically, survival rates in patients (pts) with Epstein-Barr virus (EBV)-positive (+) classic Hodgkin lymphoma (cHL) are lower than EBV− pts, in part due to increased frequency in older pts. EBV itself directly leads to increased PD-L1 expression in cHL, in addition to chromosome 9p24.1 alterations and the tumor microenvironment. This subset analysis from the S1826 trial which evaluated N-AVD versus Bv-AVD in newly diagnosed advanced-stage cHL assesses the impact of EBV status and histology on treatment outcomes. Methods: Eligible pts with stage III–IV cHL had histology confirmed by central pathology review (nodular sclerosis (NS) versus non-NS subtypes: mixed cellularity, lymphocyte-rich/depleted) and reported EBV status (IHC or ISH). Pts were randomized 1:1 to 6 cycles of N-AVD or Bv-AVD. The primary endpoint was progression-free survival (PFS). Results: Of 994 pts enrolled, 522 pts (53%) had available EBV status (EBV+ = 101; EBV− = 421). Among the 254 pts randomized to N-AVD, 48 (19%) were EBV+ and 206 were EBV-. Amongst 268 pts randomized to Bv-AVD, 53 (20%) were EBV+ and 215 were EBV-. Median age was 42 years (range 12–83) in EBV+ pts versus 25 years (range 12–80) in EBV− pts (p < 0.0001). EBV+ pts had higher IPS scores but no statistical difference in stage or B symptoms. With median follow-up of 24 months, within EBV− group, PFS was longer with N-AVD (HR 0.54; p = 0.0306); 2-year PFS of 92% (95% CI: 87–95) versus 85% (95% CI: 79–89) for Bv-AVD. In the EBV+ group, PFS was dramatically improved with N-AVD (HR 0.27; p = 0.0127); 2-year PFS of 95% (95% CI: 80–99) in N-AVD and 72% (95% CI: 58–83) in Bv-AVD. Among EBV+ patients, the treatment effect with N-AVD remained significant after adjusting for age groups (HR = 0.25; p = 0.0144). In N-AVD arm, no PFS difference was seen between EBV+ and EBV− (95% versus 92%; p = 0.88) but in Bv-AVD arm EBV+ pts had poorer PFS (72% versus 85%; p = 0.03). 102 pts had non-NS histology (N-AVD = 55; Bv-AVD = 47), median age 48 years versus 22 years for NS (p < 0.0001), and 30% non-NS were > 60 years versus 4% of NS pts > 60 years. In non-NS pts, N-AVD resulted in longer PFS (HR 0.31; 95% CI: 0.31–0.74; p = 0.005), 2-year PFS of 92% (95% CI: 79–97) versus 65% (95% CI: 50–77) for Bv-AVD. NS pts had longer PFS with N-AVD (HR 0.49; 95% CI: 0.28–0.86; p = 0.01): 2-year PFS of 94% (95% CI: 90–96) versus 87% (95% CI: 83–91). In N-AVD arm, PFS was not significantly different in non-NS 2 years PFS 92% versus 94% in NS pts (HR 2.01, p = 0.11). In Bv-AVD arm, non-NS pts had inferior PFS (HR = 3.4, p < 0.0001), 2 years PFS 65% versus 87% in NS. Conclusions: While N-AVD improves outcomes for advanced stage cHL in all pts irrespective of EBV status or histologic subtype, it substantially abrogated the historically poor outcomes in pts with EBV+ cHL and those with non-NS histologies compared with Bv-AVD. These results inform future correlative studies to understand the impact of checkpoint blockade in molecular clusters of cHL. N-AVD should be considered a standard of care for advanced-stage cHL, particularly non-NS and EBV+ cHL. Research funding declaration: Funding provided by the National Cancer Institute of the National Institutes of Health U10CA180888, U10CA180819; and in part by BMS. Keywords: immunotherapy; Hodgkin lymphoma (pediatric, adolescent, and young adult); targeting the tumor microenvironment Potential sources of conflict of interest: S. Ahmed Consultant or advisory role: ADC therapeutics, KITE/Gilead, Genmab and BMS. Other remuneration: Research funding to institution from Nektar, Merck, Xencor, Chimagen and Genmab, KITE/Gilead, Janssen, Caribou. A. F. Herrera Consultant or advisory role: Bristol Myers Squibb, Genentech, Merck, Seagen, AstraZeneca, ADC Therapeutics, Takeda, Genmab, Pfizer, Abbvie, Allogene Therapeutics Other remuneration: Research funding -Bristol Myers Squibb, Genentech, Merck, Seagen, AstraZeneca S. C. Rutherford Consultant or advisory role: Abbvie, ADC","journal":"Hematological Oncology","year":2025,"id":536275,"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":0.9507,"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":681678,"name":"Anamarija M. 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