7 | POLATUZUMAB VEDOTIN, RITUXIMAB, GEMCITABINE AND OXALIPLATIN (POLA‐R‐GEMOX) FOR RELAPSED/REFRACTORY (R/R) DIFFUSE LARGE B‐CELL LYMPHOMA (DLBCL): PHASE III POLARGO TRIAL

Introduction: Polatuzumab vedotin is approved in frontline and R/R DLBCL; the latter involving combination with bendamustine and rituximab (Tilly et al. 2022; Sehn et al. 2019). Alternative treatments are needed for patients (pts) with R/R DLBCL. We present efficacy and safety results from the randomized cohort of the POLARGO trial (NCT04182204) evaluating Pola-R-GemOx versus R-GemOx in pts with R/R DLBCL after ≥ 1 prior therapy. Methods: Following a Pola-R-GemOx safety run-in (n = 15), pts with R/R DLBCL (not otherwise specified [NOS] or transformed indolent lymphoma) ineligible for autologous stem cell transplant were randomized 1:1 to receive polatuzumab vedotin (1.8 mg/kg) plus R-GemOx (R, 375 mg/m2; Gem, 1000 mg/m2; Ox, 100 mg/m2) or R-GemOx alone every 21 days for ≤ 8 cycles. Primary endpoint was overall survival (OS). Secondary endpoints included investigator-assessed progression-free survival (PFS), and independent review committee-assessed objective response rate (ORR) and complete response rate (CRR) at end of treatment (EOT) by PET-CT. Results: In total, 270 pts with DLBCL were enrolled (median age 66 [range 20–89] years), including 176 (65.2%) pts after 1 prior therapy. Of 246 pts with DLBCL NOS, 143 (58.1%) had primary refractory disease. As of Nov 29, 2024, in the randomized cohort (N = 255; median OS follow-up 24.6 months), a statistically significant OS benefit was observed with Pola-R-GemOx (n = 129) versus R-GemOx (n = 126; hazard ratio [HR] 0.60, 95% confidence interval [CI] 0.43–0.83; p = 0.0017; Figure). Median OS was 19.5 months (95% CI: 13.3–not evaluable) for Pola-R-GemOx versus 12.5 months (95% CI: 8.9–15.8) for R-GemOx. OS benefit was consistent across most subgroups, including ABC (HR 0.53, 95% CI: 0.3–0.9) and GCB (HR 0.54, 95% CI: 0.3–0.9) subtypes by gene expression profiling. Key secondary endpoints are shown in the Table. In the safety-evaluable pts (Pola-R-GemOx, n = 128; R-GemOx, n = 125), median number of cycles received was higher with Pola-R-GemOx versus R-GemOx (7.5 versus 4.0) and Grade (Gr) 3–4 adverse event (AE) rates were similar (57.0% versus 58.4%), with higher rates of thrombocytopenia (34.4% versus 26.4%) and infections (14.1% versus 8.0%) with Pola-R-GemOx. Peripheral neuropathy (PN) was more common with Pola-R-GemOx versus R-GemOx (57.0% versus 28.8%); primarily Gr 1 (37.5% versus 23.2%). Five pts had Gr 3 PN in the Pola-R-GemOx arm. Treatment discontinuation rates due to AEs were higher with Pola-R-GemOx (23.4%) versus R-GemOx (8.0%). Gr 5 AEs were higher with Pola-R-GemOx versus R-GemOx (11.7% versus 4.0%), primarily driven by infections including COVID-19. Conclusion: Pola-R-GemOx demonstrated a statistically significant and clinically meaningful benefit in OS and PFS, with a 40% reduction in risk of death relative to R-GemOx. Pola-R-GemOx is an alternative treatment option for pts with transplant-ineligible R/R DLBCL not previously exposed to polatuzumab vedotin, which avoids the risk of T-cell depleting regimens and their potential deleterious effects on subsequent therapies. Research funding declaration: The POLARGO study was sponsored by F. Hoffmann-La Roche Ltd. Third-party editorial assistance, under the direction of the authors, was provided by Anna Nagy, BSc, of Ashfield MedComms, an Inizio company, and was funded by F. Hoffmann-La Roche Ltd. Encore Abstract: EHA 2025 Keywords: aggressive B-cell non-Hodgkin lymphoma; combination therapies Potential sources of conflict of interest: J. Sancho Consultant or advisory role: Lilly, AbbVie, Janssen, BeiGene, Roche, Gilead-Kite, BMS-Celgene, Incyte, Sobi, Miltenyi-Biomedicine Honoraria: Lilly, AbbVie, Janssen, BeiGene, Roche, Gilead-Kite, BMS-Celgene, Incyte Educational grants: Roche Other remuneration: Speaker's bureau: Gilead-Kite, BeiGene, AbbVie T. P. Vassilakopoulos Consultant or advisory role: Roche, Genesis Pharma, AbbVie, Merck, Gilead, Sandoz, Teva, AstraZeneca, Winmedica, Sobi, Swixx Honoraria: Takeda, Roche, Genesis Pharma, Merck, Glaxo, AbbVie, AstraZeneca, Gilead, Sandoz, Lilly, Janssen, Sobi, Swixx (all via institution) Educational grants: Takeda, Roche, Genesis Pharma, AbbVie, AstraZeneca, Vianex, Winmedica, Swixx, Faran Other remuneration: Research funding: Merck, Roche, AbbVie, BMS, Karyopharm (all via institution) A. Viardot Consultant or advisory role: AbbVie, Roche, AstraZeneca, BeiGene, BMS, Kite/Gilead, Incyte Honoraria: Roche Pharma AG, AbbVie, AstraZeneca, BeiGene, BMS, Kite/Gilead, Incyte Educational grants: Sobi, Janssen (Johnson & Johnson), BMS, AbbVie, Kite/Gilead A. McMillan Consultant or advisory role: Amgen, Sobi Honoraria: Amgen, Sobi L. Qiu Consultant or advisory role: BeiGene, Pfizer, AstraZeneca, Sanofi, Johnson & Johnson Educational grants: BeiGene, Pfizer, Johnson & Johnson, AstraZeneca, Sanofi Other remuneration: Speaker's bureau: Roche, BeiGene, Pfizer, Johnson & Johnson, AstraZeneca, Sanofi C. L. Batlevi Employment or leadership position: Roche/Genentech Consultant or advisory role: BMS, Seattle Genetics, Kite, Karyopharm, TG Therapeutics, ADC Therapeutics, AbbVie, Genentech, Treeline Bioscience Stock ownership: Roche Honoraria: Dava Oncology, TouchIME, Medscape Other remuneration: Research funding: Epizyme, Autolus, Roche, Vincerx R. Ibrahim Employment or leadership position: Genentech, Inc. (contractor) J. Hernandez Employment or leadership position: F. Hoffmann-La Roche Ltd Stock ownership: F. Hoffmann-La Roche Ltd Honoraria: F. Hoffmann-La Roche Ltd Educational grants: F. Hoffmann-La Roche Ltd B. McCall Employment or leadership position: Genentech/Roche Stock ownership: Roche Y. Jiang Employment or leadership position: Roche/Genentech Stock ownership: Roche Educational grants: Roche Other remuneration: Patents, royalties, other intellectual property: Roche M. Yan Employment or leadership position: Hoffmann-La Roche Stock ownership: Hoffmann-La Roche Other remuneration: Patents, royalties, other intellectual property: Hoffmann-La Roche W. Harris Employment or leadership position: Genentech, Inc. Stock ownership: Roche Other remuneration: Patents, royalties, other intellectual property: Genentech, Inc. L. Musick Employment or leadership position: Genentech, Inc./F Hoffmann-La Roche Ltd (both author and spouse are employees—within the past 2 years) Stock ownership: Genentech, Inc./F Hoffmann-La Roche Ltd, Novartis, UCB, Pfizer; spouse: Genentech, Inc./F Hoffmann-La Roche Ltd, Novartis, UCB C. Haioun Consultant or advisory role: Roche, Gilead, Incyte, AbbVie, Takeda, BeiGene, MSD Honoraria: Roche, Gilead, Incyte, AbbVie, Takeda, BeiGene, MSD Educational grants: Janssen, Roche M. Matasar Consultant or advisory role: Bayer, Genentech, Kite, Roche, Seattle Genetics Stock ownership: Merck Honoraria: ADC Therapeutics, AstraZeneca, Bayer, BMS, Celgene, Epizyme, IMV Therapeutics, Johnson & Johnson, Kite, Regeneron, Roche, Pfizer Other remuneration: Research funding: Seattle Genetics, Roche, Pharmacyclics, Genentech, Johnson & Johnson, Bayer