ABCL-073 Polatuzumab Vedotin Plus Rituximab, Cyclophosphamide, Doxorubicin, and Prednisone (Pola-R-CHP) Versus Rituximab, Cyclophosphamide, Doxorubicin, Vincristine and Prednisone (R-CHOP) Therapy in Patients With Previously Untreated Diffuse Large B-Cell Lymphoma (DLBCL): Results From the Phase III POLARIX Study

Christopher Flowers, Hervé Tilly, Franck Morschhauser, Laurie H. Sehn, Jonathan W. Friedberg, Marek Trněný, Jeff P. Sharman, Charles Herbaux, John M. Burke, Matthew Matasar, Shinya Rai, Koji Izutsu, Neha Mehta-Shah, Lucie Oberic, Adrien Chauchet, Wojciech Jurczak, Yuqin Song, Richard Greil, Larysa Mykhalska, Juan Miguel Bergua-BurguésMatthew C. Cheung, Antonio Pinto, Ho Jin Shin, Greg Hapgood, Eduardo Munhoz, Pau Abrisqueta, Jyh Pyng Gau, Jamie Hirata, Yanwen Jiang, Mark Yan, Calvin Lee, Gilles Salles

Research output: Contribution to journalArticlepeer-review

Abstract

Context: R-CHOP is the standard of care for newly diagnosed DLBCL patients; however, 40% remain uncured. Polatuzumab vedotin (Pola), a CD79b-targeting antibody-drug conjugate, has shown promising activity/safety in a Phase Ib/II study (Tilly, et al. Lancet Oncol 2019). We report the Phase III double-blind, placebo-controlled, international POLARIX study (NCT03274492), which compared Pola-R-CHP with R-CHOP in treatment-naïve DLBCL patients with an International Prognostic Index score of 2–5. Design: Patients were randomized (1:1) to six cycles of Pola-R-CHP or R-CHOP and on Day 1 of each cycle received Pola 1.8mg/kg or vincristine 1.4mg/m2, plus intravenous rituximab 375mg/m2, cyclophosphamide 750mg/m2, and doxorubicin 50mg/m2. Patients also received oral prednisone 100mg once daily (Days 1–5) and two further cycles of rituximab. The primary endpoint was investigator-assessed progression-free survival (PFS). Results: Overall, 879 patients (median age 65 [range 19–80] years) were randomized (Pola-R-CHP: n=440; R-CHOP: n=439). At primary data cut-off (28 June 2021), median follow-up was 28.2 months. PFS was superior with Pola-R-CHP vs R-CHOP (hazard ratio [HR] 0.73; 95% confidence interval [CI]: 0.57–0.95; P=0.02) and 2-year PFS rate was improved (76.7% [95% CI: 72.7–80.8] vs 70.2% [95% CI: 65.8–74.6], respectively). Investigator-assessed event-free survival favored Pola-R-CHP vs R-CHOP (HR 0.75; 95% CI: 0.58–0.96; P=0.02) and overall survival was comparable (HR 0.94; 95% CI: 0.65–1.37; P=0.75). While independent review committee-assessed end-of-treatment complete response rate by positron emission tomography-computed tomography was not significantly different with Pola-R-CHP (78.0%) vs R-CHOP (74.0%; P=0.16), disease-free survival suggested more durable responses with Pola-R-CHP vs R-CHOP (HR 0.70; 95% CI: 0.50–0.98). Safety profiles were similar for Pola-R-CHP vs R-CHOP: grade 3–4 adverse event (AE) rates, 57.7% vs 57.5%, respectively; serious AEs, 34.0% vs 30.6%; grade 5 AEs, 3.0% vs 2.3%; AEs leading to dose reduction, 9.2% vs 13.0%; and peripheral neuropathy, any grade, 52.9% vs 53.9%. At data cut-off, fewer patients treated with Pola-R-CHP (23%) vs R-CHOP (30%) had received ≥1 subsequent anti-lymphoma therapy. Conclusions: As the first-line treatment of DLBCL, Pola-R-CHP demonstrated a 27% reduction in the relative risk of disease progression, relapse, or death, and a similar safety profile, compared with R-CHOP.

Original languageEnglish
Pages (from-to)S358-S359
JournalClinical Lymphoma, Myeloma and Leukemia
Volume22
DOIs
StatePublished - Oct 2022

Keywords

  • ABCL
  • diffuse large B-cell lymphoma
  • first-line treatment
  • Phase III
  • polatuzumab vedotin
  • R-CHOP

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