Hervé Tilly1, Franck Morschhauser1, Laurie H Sehn1, Jonathan W Friedberg1, Marek Trněný1, Jeff P Sharman1, Charles Herbaux1, John M Burke1, Matthew Matasar1, Shinya Rai1, Koji Izutsu1, Neha Mehta-Shah1, Lucie Oberic1, Adrien Chauchet1, Wojciech Jurczak1, Yuqin Song1, Richard Greil1, Larysa Mykhalska1, Juan M Bergua-Burgués1, Matthew C Cheung1, Antonio Pinto1, Ho-Jin Shin1, Greg Hapgood1, Eduardo Munhoz1, Pau Abrisqueta1, Jyh-Pyng Gau1, Jamie Hirata1, Yanwen Jiang1, Mark Yan1, Calvin Lee1, Christopher R Flowers1, Gilles Salles1. 1. From the Department of Hematology and INSERM Unité 1245, Centre Henri-Becquerel and University of Rouen, Rouen (H.T.), Université de Lille, Centre Hospitalier Universitaire (CHU) Lille, ULR 7365 - GRITA - Groupe de Recherche sur les Formes Injectables et les Technologies Associées, Lille (F.M.), CHU de Montpellier, Montpellier (C.H.), the Department of Hematology, Institut Universitaire du Cancer, Toulouse-Oncopole, Toulouse (L.O.), and the Department of Hematology, Centre Hospitalier Régional Universitaire - Besançon, Besançon (A.C.) - all in France; the Centre for Lymphoid Cancer at BC Cancer and the University of British Columbia, Vancouver (L.H.S.), the Odette Cancer Centre, Sunnybrook Health Sciences Centre, University of Toronto, Toronto (M.C.C.), and F. Hoffmann-La Roche, Mississauga, ON (M.Y.) - all in Canada; the Wilmot Cancer Institute, University of Rochester, Rochester (J.W.F.), and Memorial Sloan Kettering Cancer Center, New York (M.M., G.S.) - both in New York; the First Faculty of Medicine, Charles University and the General University Hospital, Prague, Czech Republic (M.T.); the Willamette Valley Cancer Institute and Research Center, the US Oncology Network, Eugene, OR (J.P.S.); Rocky Mountain Cancer Centers, Aurora, CO (J.M.B.); Memorial Sloan Kettering Cancer Center, Montvale, NJ (M.M.); the Department of Hematology and Rheumatology, Kindai University, Faculty of Medicine, Osaka-Sayama City (S.R.), and the National Cancer Center Hospital, Tokyo (K.I.) - both in Japan; Washington University in St. Louis, St. Louis (N.M.-S.); the Maria Sklodowska-Curie National Research Institute of Oncology, Krakow, Poland (W.J.); Peking University Cancer Hospital, Beijing (Y.S.); the 3rd Medical Department, Paracelsus Medical University, Salzburg Cancer Research Institute-Center for Clinical Cancer and Immunology Trials, and Cancer Cluster Salzburg, Salzburg, Austria (R.G.); the Feofaniya Clinical Hospital, Kyiv, Ukraine (L.M.); Hospital San Pedro de Alcántara, Cáceres (J.M.B.-B.), and the Department of Hematology, Vall d'Hebron University Hospital, Vall d'Hebron Institute of Oncology, Barcelona (P.A.) - both in Spain; the Hematology-Oncology and Stem Cell Transplantation Unit, Istituto Nazionale Tumori, Fondazione G. Pascale, IRCCS, Naples, Italy (A.P.); the Division of Hematology-Oncology, Department of Internal Medicine, Research Institute of Medical Science, Pusan National University Hospital, Pusan National University School of Medicine, Busan, South Korea (H.-J.S.); Princess Alexandra Hospital, Brisbane, QLD, Australia (G.H.); Hospital Erasto Gaertner, Curitiba, Brazil (E.M.); Taipei Veterans General Hospital, Taipei, Taiwan (J.-P.G.); Genentech, South San Francisco, CA (J.H., Y.J., C.L.); and M.D. Anderson Cancer Center, Houston (C.R.F.).
Abstract
BACKGROUND: Diffuse large B-cell lymphoma (DLBCL) is typically treated with rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP). However, only 60% of patients are cured with R-CHOP. Polatuzumab vedotin is an antibody-drug conjugate targeting CD79b, which is ubiquitously expressed on the surface of malignant B cells. METHODS: We conducted a double-blind, placebo-controlled, international phase 3 trial to evaluate a modified regimen of R-CHOP (pola-R-CHP), in which vincristine was replaced with polatuzumab vedotin, as compared with standard R-CHOP, in patients with previously untreated intermediate-risk or high-risk DLBCL. Patients 18 to 80 years of age were randomly assigned in a 1:1 ratio to receive six cycles of either pola-R-CHP or R-CHOP, plus two cycles of rituximab alone. The primary end point was investigator-assessed progression-free survival. Secondary end points included overall survival and safety. RESULTS: Overall, 879 patients underwent randomization: 440 were assigned to the pola-R-CHP group and 439 to the R-CHOP group. After a median follow-up of 28.2 months, the percentage of patients surviving without progression was significantly higher in the pola-R-CHP group than in the R-CHOP group (76.7% [95% confidence interval (CI), 72.7 to 80.8] vs. 70.2% [95% CI, 65.8 to 74.6] at 2 years; stratified hazard ratio for progression, relapse, or death, 0.73 by Cox regression; 95% CI, 0.57 to 0.95; P = 0.02). Overall survival at 2 years did not differ significantly between the groups (88.7% [95% CI, 85.7 to 91.6] in the pola-R-CHP group and 88.6% [95% CI, 85.6 to 91.6] in the R-CHOP group; hazard ratio for death, 0.94; 95% CI, 0.65 to 1.37; P = 0.75). The safety profile was similar in the two groups. CONCLUSIONS: Among patients with previously untreated intermediate-risk or high-risk DLBCL, the risk of disease progression, relapse, or death was lower among those who received pola-R-CHP than among those who received R-CHOP. (Funded by F. Hoffmann-La Roche/Genentech; POLARIX ClinicalTrials.gov number, NCT03274492.).
BACKGROUND: Diffuse large B-cell lymphoma (DLBCL) is typically treated with rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP). However, only 60% of patients are cured with R-CHOP. Polatuzumab vedotin is an antibody-drug conjugate targeting CD79b, which is ubiquitously expressed on the surface of malignant B cells. METHODS: We conducted a double-blind, placebo-controlled, international phase 3 trial to evaluate a modified regimen of R-CHOP (pola-R-CHP), in which vincristine was replaced with polatuzumab vedotin, as compared with standard R-CHOP, in patients with previously untreated intermediate-risk or high-risk DLBCL. Patients 18 to 80 years of age were randomly assigned in a 1:1 ratio to receive six cycles of either pola-R-CHP or R-CHOP, plus two cycles of rituximab alone. The primary end point was investigator-assessed progression-free survival. Secondary end points included overall survival and safety. RESULTS: Overall, 879 patients underwent randomization: 440 were assigned to the pola-R-CHP group and 439 to the R-CHOP group. After a median follow-up of 28.2 months, the percentage of patients surviving without progression was significantly higher in the pola-R-CHP group than in the R-CHOP group (76.7% [95% confidence interval (CI), 72.7 to 80.8] vs. 70.2% [95% CI, 65.8 to 74.6] at 2 years; stratified hazard ratio for progression, relapse, or death, 0.73 by Cox regression; 95% CI, 0.57 to 0.95; P = 0.02). Overall survival at 2 years did not differ significantly between the groups (88.7% [95% CI, 85.7 to 91.6] in the pola-R-CHP group and 88.6% [95% CI, 85.6 to 91.6] in the R-CHOP group; hazard ratio for death, 0.94; 95% CI, 0.65 to 1.37; P = 0.75). The safety profile was similar in the two groups. CONCLUSIONS: Among patients with previously untreated intermediate-risk or high-risk DLBCL, the risk of disease progression, relapse, or death was lower among those who received pola-R-CHP than among those who received R-CHOP. (Funded by F. Hoffmann-La Roche/Genentech; POLARIX ClinicalTrials.gov number, NCT03274492.).
Authors: Miguel-Angel Perales; Larry D Anderson; Tania Jain; Saad S Kenderian; Olalekan O Oluwole; Gunjan L Shah; Jakub Svoboda; Mehdi Hamadani Journal: Transplant Cell Ther Date: 2022-06-26
Authors: Sotirios G Papageorgiou; Thomas P Thomopoulos; Athanasios Liaskas; Theodoros P Vassilakopoulos Journal: Cancers (Basel) Date: 2022-04-10 Impact factor: 6.575
Authors: R Andrew Harkins; Sharvil P Patel; Michelle J Lee; Jeffrey M Switchenko; Stephen M Ansell; Nancy L Bartlett; Kristie A Blum; Amanda F Cashen; Carla Casulo; Jonathan W Friedberg; Patrick B Johnston; Brad S Kahl; John P Leonard; Brian K Link; Izidore S Lossos; Peter Martin; Matt J Maurer; Neha Mehta-Shah; Patrick M Reagan; Jason R Westin; Jean L Koff; Christopher R Flowers Journal: Blood Adv Date: 2022-05-10