POLATUZUMAB VEDOTIN, RITUXIMAB, GEMCITABINE AND OXALIPLATIN (POLA-R-GEMOX) FOR RELAPSED/REFRACTORY (R/R) DIFFUSE LARGE B-CELL LYMPHOMA (DLBCL): PHASE III POLARGO TRIAL
J. Sancho, Z. Li, T. P. Vassilakopoulos, A. Viardot, A. McMillan, M. Sinan Dal, J. Pereira, J. S. Kim, L. Qiu, C. L. Batlevi, R. Ibrahim, J. Hernandez, B. McCall, Y. Jiang, M. Yan, W. Harris, L. Musick, C. Haioun, M. Matasar
{"title":"POLATUZUMAB VEDOTIN, RITUXIMAB, GEMCITABINE AND OXALIPLATIN (POLA-R-GEMOX) FOR RELAPSED/REFRACTORY (R/R) DIFFUSE LARGE B-CELL LYMPHOMA (DLBCL): PHASE III POLARGO TRIAL","authors":"J. Sancho, Z. Li, T. P. Vassilakopoulos, A. Viardot, A. McMillan, M. Sinan Dal, J. Pereira, J. S. Kim, L. Qiu, C. L. Batlevi, R. Ibrahim, J. Hernandez, B. McCall, Y. Jiang, M. Yan, W. Harris, L. Musick, C. Haioun, M. Matasar","doi":"10.1002/hon.70093_7","DOIUrl":null,"url":null,"abstract":"<p><b>Introduction:</b> 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.</p><p><b>Methods:</b> Following a Pola-R-GemOx safety run-in (<i>n</i> = 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/m<sup>2</sup>; Gem, 1000 mg/m<sup>2</sup>; Ox, 100 mg/m<sup>2</sup>) 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.</p><p><b>Results:</b> 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 (<i>N</i> = 255; median OS follow-up 24.6 months), a statistically significant OS benefit was observed with Pola-R-GemOx (<i>n</i> = 129) versus R-GemOx (<i>n</i> = 126; hazard ratio [HR] 0.60, 95% confidence interval [CI] 0.43–0.83; <i>p</i> = 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, <i>n</i> = 128; R-GemOx, <i>n</i> = 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.</p><p><b>Conclusion:</b> 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.</p><p><b>Research</b> <b>funding declaration:</b> 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.</p><p><b>Encore Abstract:</b> EHA 2025</p><p><b>Keywords:</b> aggressive B-cell non-Hodgkin lymphoma; combination therapies</p><p><b>Potential sources of conflict of interest:</b></p><p><b>J. Sancho</b></p><p><b>Consultant or advisory role:</b> Lilly, AbbVie, Janssen, BeiGene, Roche, Gilead-Kite, BMS-Celgene, Incyte, Sobi, Miltenyi-Biomedicine</p><p><b>Honoraria:</b> Lilly, AbbVie, Janssen, BeiGene, Roche, Gilead-Kite, BMS-Celgene, Incyte</p><p><b>Educational</b> <b>grants:</b> Roche</p><p><b>Other remuneration:</b> Speaker's bureau: Gilead-Kite, BeiGene, AbbVie</p><p><b>T. P. Vassilakopoulos</b></p><p><b>Consultant or advisory role:</b> Roche, Genesis Pharma, AbbVie, Merck, Gilead, Sandoz, Teva, AstraZeneca, Winmedica, Sobi, Swixx</p><p><b>Honoraria:</b> Takeda, Roche, Genesis Pharma, Merck, Glaxo, AbbVie, AstraZeneca, Gilead, Sandoz, Lilly, Janssen, Sobi, Swixx (all via institution)</p><p><b>Educational</b> <b>grants:</b> Takeda, Roche, Genesis Pharma, AbbVie, AstraZeneca, Vianex, Winmedica, Swixx, Faran</p><p><b>Other remuneration:</b> Research funding: Merck, Roche, AbbVie, BMS, Karyopharm (all via institution)</p><p><b>A. Viardot</b></p><p><b>Consultant or advisory role:</b> AbbVie, Roche, AstraZeneca, BeiGene, BMS, Kite/Gilead, Incyte</p><p><b>Honoraria:</b> Roche Pharma AG, AbbVie, AstraZeneca, BeiGene, BMS, Kite/Gilead, Incyte</p><p><b>Educational</b> <b>grants:</b> Sobi, Janssen (Johnson & Johnson), BMS, AbbVie, Kite/Gilead</p><p><b>A. McMillan</b></p><p><b>Consultant or advisory role:</b> Amgen, Sobi</p><p><b>Honoraria:</b> Amgen, Sobi</p><p><b>L. Qiu</b></p><p><b>Consultant or advisory role:</b> BeiGene, Pfizer, AstraZeneca, Sanofi, Johnson & Johnson</p><p><b>Educational</b> <b>grants:</b> BeiGene, Pfizer, Johnson & Johnson, AstraZeneca, Sanofi</p><p><b>Other remuneration:</b> Speaker's bureau: Roche, BeiGene, Pfizer, Johnson & Johnson, AstraZeneca, Sanofi</p><p><b>C. L. Batlevi</b></p><p><b>Employment or leadership position:</b> Roche/Genentech</p><p><b>Consultant or advisory role:</b> BMS, Seattle Genetics, Kite, Karyopharm, TG Therapeutics, ADC Therapeutics, AbbVie, Genentech, Treeline Bioscience</p><p><b>Stock ownership:</b> Roche</p><p><b>Honoraria:</b> Dava Oncology, TouchIME, Medscape</p><p><b>Other remuneration:</b> Research funding: Epizyme, Autolus, Roche, Vincerx</p><p><b>R. Ibrahim</b></p><p><b>Employment or leadership position:</b> Genentech, Inc. (contractor)</p><p><b>J. Hernandez</b></p><p><b>Employment or leadership position:</b> F. Hoffmann-La Roche Ltd</p><p><b>Stock ownership:</b> F. Hoffmann-La Roche Ltd</p><p><b>Honoraria:</b> F. Hoffmann-La Roche Ltd</p><p><b>Educational</b> <b>grants:</b> F. Hoffmann-La Roche Ltd</p><p><b>B. McCall</b></p><p><b>Employment or leadership position:</b> Genentech/Roche</p><p><b>Stock ownership:</b> Roche</p><p><b>Y. Jiang</b></p><p><b>Employment or leadership position:</b> Roche/Genentech</p><p><b>Stock ownership:</b> Roche</p><p><b>Educational</b> <b>grants:</b> Roche</p><p><b>Other remuneration:</b> Patents, royalties, other intellectual property: Roche</p><p><b>M. Yan</b></p><p><b>Employment or leadership position:</b> Hoffmann-La Roche</p><p><b>Stock ownership:</b> Hoffmann-La Roche</p><p><b>Other remuneration:</b> Patents, royalties, other intellectual property: Hoffmann-La Roche</p><p><b>W. Harris</b></p><p><b>Employment or leadership position:</b> Genentech, Inc.</p><p><b>Stock ownership:</b> Roche</p><p><b>Other remuneration:</b> Patents, royalties, other intellectual property: Genentech, Inc.</p><p><b>L. Musick</b></p><p><b>Employment or leadership position:</b> Genentech, Inc./F Hoffmann-La Roche Ltd (both author and spouse are employees—within the past 2 years)</p><p><b>Stock ownership:</b> Genentech, Inc./F Hoffmann-La Roche Ltd, Novartis, UCB, Pfizer; spouse: Genentech, Inc./F Hoffmann-La Roche Ltd, Novartis, UCB</p><p><b>C. Haioun</b></p><p><b>Consultant or advisory role:</b> Roche, Gilead, Incyte, AbbVie, Takeda, BeiGene, MSD</p><p><b>Honoraria:</b> Roche, Gilead, Incyte, AbbVie, Takeda, BeiGene, MSD</p><p><b>Educational</b> <b>grants:</b> Janssen, Roche</p><p><b>M. Matasar</b></p><p><b>Consultant or advisory role:</b> Bayer, Genentech, Kite, Roche, Seattle Genetics</p><p><b>Stock ownership:</b> Merck</p><p><b>Honoraria:</b> ADC Therapeutics, AstraZeneca, Bayer, BMS, Celgene, Epizyme, IMV Therapeutics, Johnson & Johnson, Kite, Regeneron, Roche, Pfizer</p><p><b>Other remuneration:</b> Research funding: Seattle Genetics, Roche, Pharmacyclics, Genentech, Johnson & Johnson, Bayer</p>","PeriodicalId":12882,"journal":{"name":"Hematological Oncology","volume":"43 S3","pages":""},"PeriodicalIF":3.3000,"publicationDate":"2025-06-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/hon.70093_7","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Hematological Oncology","FirstCategoryId":"3","ListUrlMain":"https://onlinelibrary.wiley.com/doi/10.1002/hon.70093_7","RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q2","JCRName":"HEMATOLOGY","Score":null,"Total":0}
引用次数: 0
Abstract
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.
Researchfunding 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.
期刊介绍：
Hematological Oncology considers for publication articles dealing with experimental and clinical aspects of neoplastic diseases of the hemopoietic and lymphoid systems and relevant related matters. Translational studies applying basic science to clinical issues are particularly welcomed. Manuscripts dealing with the following areas are encouraged:
-Clinical practice and management of hematological neoplasia, including: acute and chronic leukemias, malignant lymphomas, myeloproliferative disorders
-Diagnostic investigations, including imaging and laboratory assays
-Epidemiology, pathology and pathobiology of hematological neoplasia of hematological diseases
-Therapeutic issues including Phase 1, 2 or 3 trials as well as allogeneic and autologous stem cell transplantation studies
-Aspects of the cell biology, molecular biology, molecular genetics and cytogenetics of normal or diseased hematopoeisis and lymphopoiesis, including stem cells and cytokines and other regulatory systems.
Concise, topical review material is welcomed, especially if it makes new concepts and ideas accessible to a wider community. Proposals for review material may be discussed with the Editor-in-Chief. Collections of case material and case reports will be considered only if they have broader scientific or clinical relevance.
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