288 | FIVE‐YEAR ANALYSIS OF AN ASIA SUBPOPULATION WITH PREVIOUSLY UNTREATED DLBCL CONFIRMS POLA‐R‐CHP BENEFIT ON OUTCOMES: THE POLARIX STUDY

Introduction: The extended 5-year follow-up analysis of POLARIX (NCT0327449) demonstrated sustained and significant progression-free survival (PFS) and disease-free survival (DFS) benefits for previously untreated diffuse large B cell lymphoma (DLBCL) patients receiving polatuzumab vedotin plus rituximab, cyclophosphamide, doxorubicin, and prednisone (Pola-R-CHP) versus rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP). Numerically fewer deaths, especially lymphoma-related deaths, were observed in patients receiving Pola-R-CHP versus R-CHOP (Salles et al. ASH 2024). Here, we report the 5-year results of the Asia subpopulation of this study including molecular outcomes. Methods: Eligible DLBCL patients (18–80 years) were randomized 1:1 to six cycles of Pola-R-CHP or R-CHOP plus two cycles of rituximab alone (Tilly et al. NEJM 2022, Song et al. Blood 2023). The primary endpoint was investigator (INV)-assessed PFS. Secondary end points included INV-assessed event-free survival (EFS), overall survival (OS) and safety. Results: In total, 281 patients were included (China mainland, 150; Japan, 85; Korea, 31; and China Taiwan, 15); 141 were randomized to Pola-R-CHP and 140 to R-CHOP. At time of data cut-off (5 July 2024; median follow-up of 60.0 months [range 0–74]), the 5-year PFS rates were 64.0% (95% CI: 55.01–72.90) in Pola-R-CHP versus 57.3% (95% CI: 48.25–66.27) in R-CHOP (HR 0.74; 95% CI: 0.50–1.10). The 5-year EFS rates for Pola-R-CHP versus R-CHOP were 63.4% (95% CI: 54.51–72.37) versus 53.5% (95% CI: 43.22–63.76) (HR 0.72; 95% CI: 0.49–1.06), respectively. The 5-year OS estimates were 84.6% (95% CI: 78.28–90.92) in Pola-R-CHP versus 77.7% (95% CI: 70.30–85.05) in R-CHOP (HR 0.65; 95% CI: 0.37–1.14). Fewer patients died in the Pola-R-CHP arm (14 deaths, 14.9%) versus R-CHOP arm (21 deaths, 21.4%), showing a trend of OS benefit. Exploratory data also showed a trend toward better 5-year PFS rates with Pola-R-CHP over R-CHOP in high-risk subgroup including patients with double expression lymphoma (DEL) (58.3% vs. 51.1%, HR 0.65, 95% CI: 0.32–1.29), activated B-cell subtype (ABC) (73.1% vs. 53.9%, HR 0.44, 95% CI: 0.23–0.85), low M1-polarized macrophage infiltration levels (M1low) (73.5% vs. 58.8%, HR 0.52, 95% CI: 0.23–1.16) and positive dark zone signature (DZsig) (87.5% vs. 62.5%, HR 0.29, 95% CI: 0.04–2.44). The safety profile was comparable between Pola-R-CHP and R-CHOP, including rates of grade 3 to 5 adverse events (AEs; 75.0% vs. 68.3%, respectively), serious AEs (32.9% vs. 32.4%), grade 5 AEs (1.4% vs. 0.7%), any grade of peripheral neuropathy (45.0% vs. 51.8%) and AEs leading to study treatment discontinuation (5.7% vs. 7.2%). Conclusions: Pola-R-CHP continues to demonstrate a clinically meaningful benefit in INV-assessed PFS compared with R-CHOP in Asia subpopulation. With longer follow-up, there are numerically fewer deaths observed with the treatment, indicating a stable effect on OS. No new safety signals have been identified. Research funding declaration: This study was sponsored by Genentech, Inc and F. Hoffmann-La Roche Ltd. Keywords: Aggressive B-cell non-Hodgkin lymphoma; Molecular Targeted Therapies; Combination Therapies Potential sources of conflict of interest: H. Goto Honoraria: Chugai, Abbvie, BMS, Novartis, Gilead, Kyowa Kirin, Takeda, Meiji and MSD Other remuneration: Research funding: Sanofi, BMS, Gilead, Kyowa Kirin, Symbio D. H. Yoon Consultant or advisory role: Abclon, Beigene, BMS, GI cell, GC cell, Verismo, Janssen, Novartis, Roche and Pharos Bio Honoraria: Amgen, Antengene, BMS, Boryung, GSK, Kyowa Kirin, Novartis, Roche, Takeda and Janssen Other remuneration: Research funding: Abbvie, Beigene, Boryung, Celltrion, Kyowa Kirin, Janssen, Samyang and Sanofi D. Maruyama Consultant or advisory role: Janssen, AstraZeneca, Chugai, Roche, AbbVie, Genmab, Sanofi, BMS, Pfizer Honoraria: Ono, Nippon Shinyaku, Janssen, Mundipharma, Eisai, Chugai, Kyowa Kirin, MSD, Zenyaku, Sanofi, Symbio, Takeda, AbbVie, AstraZeneca, BMS, Genmab, Novartis, Pfizer and Roche G. Salles Consultant or advisory role: Abbvie, Ellipses, Genentech/Roche, Genmab, Innate Pharma, Incyte, Kite/Gilead, Modex, Orna Therapeutics, Treeline Other remuneration: Membership on advisory committees: Abbvie, Beigene, BMS, Foresight, Genentech/Roche, Genmab, Janssen, Ipsen, Incyte, Kite/Gilead, Lilly, Merck, Novartis, Nurix, Pfizer, SERB pharmaceuticals. Research funding: Abbvie, Genentech, Genmab, Janssen, Ipsen L. Bu Employment or leadership position: Roche Y. Jiang Employment or leadership position: Genentech S. Chohan Employment or leadership position: Roche M. Sugidono Employment or leadership position: Roche Stock ownership: Roche C. L. Batlevi Employment or leadership position: Roche Stock ownership: Roche M. Yan Employment or leadership position: Roche Stock ownership: Roche C. Xu Employment or leadership position: Roche S. Huang Employment or leadership position: Roche W. Li Employment or leadership position: Roche Y. Zhang Employment or leadership position: Roche K. Izutsu Consultant or advisory role: MSD, AstraZeneca, Abbvie, Bristol Myers Squibb, Novartis, Yakult, Kyowa Kirin, Chugai, Beigene, Genmab, Otsuka, Ono Pharma, Mitsubishi Tanabe Pharmaceutical, Eisai, Symbio, Taked, Zenyakua, Carna Biosciences, Nihon Shinyaku Honoraria: AstraZeneca, Abbvie, Bristol Myers Squibb, Novartis, Pfizer, Janssen, Kyowa Kirin, Daiichi Sankyo, Chugai, Genmab, Gilead, Ono Pharmac, Nihon Kayakueutical, Symbio, Takeda, Lilly, Astellas, Meiji Seika Pharma.

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