{"doi":"10.1002/hon.3163_5","title":"NIVOLUMAB(N)‐AVD IMPROVES PROGRESSION‐FREE SURVIVAL COMPARED TO BRENTUXIMAB VEDOTIN(BV)‐AVD IN ADVANCED STAGE (AS) CLASSIC HODGKIN LYMPHOMA (HL): RESULTS OF SWOG S1826","abstract":"Background: The addition of BV to initial chemotherapy improves outcomes in adult and pediatric patients (pts) with AS HL. However, frontline BV adds toxicity, most pediatric pts receive radiation therapy (RT), and 7%–20% of pts still develop relapsed/refractory (RR) HL. The PD-1 pathway is central to the pathogenesis of HL and PD-1 blockade is effective in RR HL. The adult and pediatric cooperative groups of the National Clinical Trials Network (NCTN) conducted the randomized, phase 3 S1826 trial to evaluate N-AVD versus BV-AVD in pts with newly diagnosed AS HL. Methods: Eligible pts were ≥12 years (y) with stage 3–4 HL. Pts were randomized 1:1 to either 6 cycles of N-AVD or BV-AVD. G-CSF neutropenia prophylaxis was required with BV-AVD versus optional with N-AVD. Pre-specified pts could receive RT to residually metabolically active lesions on end of treatment PET. Pts were stratified by age, international prognostic score (IPS), and intent to use RT. Response and disease progression were assessed by investigators using 2014 Lugano Classification. The primary endpoint was progression-free survival (PFS); secondary endpoints included overall survival (OS), event-free survival, patient-reported outcomes (PROs), and safety. Results: 994 pts were enrolled from 7/9/19 to 10/5/22; 976 were eligible and randomized to N-AVD (n = 489) or BV-AVD (n = 487). Median age was 27y (range 12–83y), 56% of pts were male, 76% were white, 12% were black, and 13% were Hispanic. 24% of pts were <18y, 10% were > 60y, and 32% had IPS 4–7. To date, <1% of pts received RT. At the planned 2nd interim analysis (50% of total PFS events) the SWOG Data and Safety Monitoring Committee recommended to report the primary results because the primary PFS endpoint crossed the protocol-specified conservative statistical boundary. 30 PFS events occurred after N-AVD versus 58 events after BV-AVD. With a median follow-up of 12.1 months, PFS was superior in the N-AVD arm (HR 0.48, 99% CI 0.27–0.87, one-sided p = 0.0005); 1y PFS: N-AVD, 94%, BV-AVD, 86% (Figure). 11 deaths (7 due to adverse events, AE) were observed after BV-AVD compared to 4 after N-AVD (3 due to AE). The rate of grade (gr) ≥3 hematologic AE was 48.4% (45.1% gr ≥3 neutropenia) after N-AVD compared to 30.5% (23.9% gr ≥3 neutropenia) after BV-AVD. Rates (any gr) of febrile neutropenia (5.6% N vs. 6.4% BV), pneumonitis (2.0% N vs. 3.2% BV), ALT elevation (30.7% N vs. 39.8% BV), and colitis (1% N vs. 1.3% BV) were similar. Hypo/hyperthyroidism was more frequent after N-AVD (7%/3% N vs. <1% BV) while peripheral neuropathy was more common after BV-AVD (sensory: 28.1%, 1.2% gr ≥ 3 N vs. 54.2%,7.8% gr ≥ 3 BV; motor: 4% N vs. 6.8% BV). Encore Abstract—previously submitted to ASCO 2023 The research was funded by: Funding provided by the National Cancer Institute of the National Institutes of Health U10CA180888, U10CA180819, U10CA180821, U10CA180820, U10CA180863, UG1CA189955 and funding and drug provided by Bristol-Myers Squibb, drug provided by SeaGen for patients enrolled in Canada. Keywords: Hodgkin lymphoma, immunotherapy, targeting the tumor microenvironment Conflicts of interests pertinent to the abstract A. F. Herrera Consultant or advisory role: Bristol-Myers Squib, Genentech, Merck, SeaGen, AstraZeneca, Karyopharm, ADC Therapeutics, Takeda, Tubulis, Regeneron, Genmab, Pfizer, Caribou Biosciences, Adicet Bio, Abbvie, Allogene Therapeutics, Roche Diagnostics Research funding: Bristol-Myers Squib, Genentech, Merck, SeaGen, KITE Pharma/Gilead Sciences, AstraZeneca, ADC Therapeutics S. M. Castellino Consultant or advisory role: SeaGen Inc. scientific advisory board; no honorarium taken S. C. Rutherford Consultant or advisory role: ADC Therapeutics, Genmab, Karyopharm, Kite, SeaGen Research funding: Genentech, Karyopharm A. M. Evens Consultant or advisory role: Seattle Genetics, Hutchmed, Incyte, Daiichi Sankyo, Epizyme, Novartis, Abbvie, and Pharmacyclics K. Davison Consultant or advisory role: BMS, SeaGen S.","journal":"Hematological Oncology","year":2023,"id":334648,"datarank":0.4636563680037475,"base_score":3.091042453358316,"endowment":3.091042453358316,"self_citation_contribution":0.4636563680037475,"citation_network_contribution":0.0,"self_endowment_contribution":0.4636563680037475,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":21,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9522,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2023-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":268627,"name":"Michael LeBlanc","orcid":"0000-0001-7192-2860","position":1,"is_corresponding":false},{"id":282785,"name":"Sharon M. 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