Clinical Lymphoma, Myeloma & Leukemia, Vol.22, Suppl.2 - October 2022

Abstracts Clinical Lymphoma, Myeloma & Leukemia October 2022 S358 relapses. R-mNHL-BFM-90 program is highly effective in de novo DLBCL NOS adult patients. R-mNHL-BFM-90 therapy toxicity is acceptable. The estimated CR duration probability within 10 months after treatment completion in the high-risk group is 100% in R-mNHL-BFM-90 group compared to 5 7 % in R-DA- EPOCH group (  2 test, p=0.004 7 ). Keywords: ABCL, DLBCL, randomized study, R-DA-EPOCH-21, R-mNHL-BFM-90 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 MD 1 , Hervé Tilly MD 2 , Franck Morschhauser MD, PhD 3 , Laurie H. Sehn MD 4 , Jonathan W. Friedberg MD 5 , Marek Trn ě ný MD 6 , Jeff P. Sharman MD 7 , Charles Herbaux MD 8 , John M. Burke MD 9 , Matthew Matasar MD 10 , Shinya Rai MD, PhD 11 , Koji Izutsu MD, PhD 12 , Neha Mehta-Shah MD 13 , Lucie Oberic MD 14 , Adrien Chauchet MD 15 , Wojciech Jurczak MD, PhD 16 , Yuqin Song MD 17 , Richard Greil MD 18 , Larysa Mykhalska MD 19 , Juan Miguel Bergua- Burgués MD 20 , Matthew C. Cheung MD, MSc 21 , Antonio Pinto MD 22 , Ho-Jin Shin MD, PhD 23 , Greg Hapgood MD, PhD 24 , Eduardo Munhoz MD 25 , Pau Abrisqueta MD, PhD 26 , Jyh-Pyng Gau MD 27 , Jamie Hirata PharmD 28 , Yanwen Jiang PhD 28 , Mark Yan PhD 29 , Calvin Lee MD 28 , Gilles Salles MD, PhD 30 1 The University of Texas MD Anderson Cancer Center, Houston, USA. 2 Centre Henri Becquerel and University of Rouen, Rouen, France. 3 Univ. Lille, CHU Lille, ULR 7365 – GRITA – Group de Recherche sur les formes Injectables et les Technologies Associées, Lille, France. 4 BC Cancer Centre for Lymphoid Cancer and the University of British Columbia, Vancouver, Canada. 5 Wilmot Cancer Institute, University of Rochester, Rochester, USA. 6 First Faculty of Medicine, Charles University, General Hospital, Prague, Czech Republic. 7 Willamette Valley Cancer Institute/ US Oncology, Eugene, USA. 8 CHU de Montpellier, Montpellier, France. 9 Rocky Mountain Cancer Centers/US Oncology, Aurora, USA. 10 Memorial Sloan Kettering Cancer Center, New York City/Montvale, USA. 11 Kindai University, Faculty of Medicine, Osaka-Sayama City, Japan. 12 National Cancer Center Hospital, Tokyo, Japan. 13 Washington University in St. Louis, St. Louis, USA. 14 Institut Universitaire du Cancer, Toulouse-Oncopole, Toulouse, France. 15 CHRU Besançon, Besançon, France. 16 Maria Sklodowska – Curie National Research Institute of Oncology, Krakow, Poland. 17 Peking University Cancer Hospital, Beijing, China. 18 Paracelsus Medical University, Salzburg Cancer Research Institute-CCCIT and Cancer Cluster Salzburg, Salzburg, Austria. 19 Clinical Hospital Feofaniya, Kyiv, Ukraine. 20 Hospital San Pedro de Alcántara, Cáceres, Spain. 21 Odette Cancer Centre, Sunnybrook Health Sciences Centre, University of Toronto, Toronto, Canada. 22 Hematology-Oncology & Stem Cell Transplantation Unit, Istituto Nazionale Tumori, Fondazione ‘G. Pascale’, IRCCS, Naples, Italy. 23 Medical Research Institute, Pusan National University Hospital, Pusan National University School of Medicine, Busan, Korea, Republic of. 24 Princess Alexandra Hospital, Brisbane, Australia. 25 Hospital Erasto Gaertner, Curitiba, Brazil. 26 Hospital Vall d’Hebron, Vall d’Hebron Institute of Oncology (VHIO), Barcelona, Spain. 27 Taipei Veterans General Hospital, Taipei, Taiwan. 28 Genentech, Inc., South San Francisco, USA. 29 Hoffmann-La Roche Ltd, Mississauga, Canada. 30 Memorial Sloan Kettering Cancer Center, New York City, USA Co n text: R-CHOP is the standard of care for newly diagnosed DLBCL patients; however, 40% remain uncured. Polatuzumab vedotin (Pola), a CD 7 9b-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 (NCT032 7 4492), which compared Pola-R-CHP with R-CHOP in treatment-naïve DLBCL patients with an International Prognostic Index score of 2–5. D esig n : 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 3 7 5mg/m 2 , cyclophosphamide 7 50mg/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, 8 7 9 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. 7 3; 95% confidence interval [CI]: 0.5 7 –0.95; P=0.02) and 2-year PFS rate was improved ( 7 6. 7 % [95% CI: 7 2. 7 –80.8] vs 7 0.2% [95% CI: 65.8– 7 4.6], respectively). Investigator-assessed event-free survival favored Pola-R-CHP vs R-CHOP (HR 0. 7 5; 95% CI: 0.58–0.96; P=0.02) and overall survival was comparable (HR 0.94; 95% CI: 0.65–1.3 7 ; P=0. 7 5). 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 ( 7 8.0%) vs R-CHOP ( 7 4.0%; P=0.16), disease-free survival suggested more durable responses with Pola-R-CHP vs R-CHOP (HR 0. 7 0; 95% CI: 0.50–0.98). Safety profiles were similar for Pola-R-CHP vs R-CHOP: grade 3–4 adverse event (AE) rates, 5 7 . 7 % vs 5 7 .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. Co n clusio n s: As the first-line treatment of DLBCL, Pola-R-CHP demonstrated a 2 7 % reduction in the relative risk of disease progression, relapse, or death, and a similar safety profile, compared with R-CHOP.