TY - JOUR
T1 - Polatuzumab Vedotin in Previously Untreated Diffuse Large B-Cell Lymphoma
AU - Tilly, Hervé
AU - Morschhauser, Franck
AU - Sehn, Laurie H.
AU - Friedberg, Jonathan W.
AU - Trněný, Marek
AU - Sharman, Jeff P.
AU - Herbaux, Charles
AU - Burke, John M.
AU - Matasar, Matthew
AU - Rai, Shinya
AU - Izutsu, Koji
AU - Mehta-Shah, Neha
AU - Oberic, Lucie
AU - Chauchet, Adrien
AU - Jurczak, Wojciech
AU - Song, Yuqin
AU - Greil, Richard
AU - Mykhalska, Larysa
AU - Bergua-Burgués, Juan M.
AU - Cheung, Matthew C.
AU - Pinto, Antonio
AU - Shin, Ho Jin
AU - Hapgood, Greg
AU - Munhoz, Eduardo
AU - Abrisqueta, Pau
AU - Gau, Jyh Pyng
AU - Hirata, Jamie
AU - Jiang, Yanwen
AU - Yan, Mark
AU - Lee, Calvin
AU - Flowers, Christopher R.
AU - Salles, Gilles
N1 - Funding Information:
The POLARIX trial is a randomized, double-blind, placebo-controlled, international phase 3 trial. The protocol, which is available with the full text of this article at NEJM.org, was approved by the institutional review board or ethics committee at each participating institution. The trial was conducted in accordance with the Good Clinical Practice guidelines of the International Council for Harmonisation of Technical Requirements for Pharmaceuticals for Human Use and the principles of the Declaration of Helsinki.24 All the patients provided written informed consent. The trial was sponsored by F. Hoffmann–La Roche/ Genentech and was designed by the sponsor in collaboration with the Lymphoma Study Association. An independent data and safety monitoring committee reviewed safety data on a regular basis during the conduct of the trial. The first draft of the manuscript was written primarily by one academic author and one author employed by the sponsor; medical writing assistance was funded by the sponsor. All the authors reviewed the data and contributed to the preparation of the final version of the manuscript. The authors vouch for the completeness and accuracy of the data and for the fidelity of the trial to the protocol and statistical analysis plan.
Publisher Copyright:
Copyright © 2021 Massachusetts Medical Society.
PY - 2022/1/27
Y1 - 2022/1/27
N2 - 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 polaR-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.
AB - 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 polaR-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.
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U2 - 10.1056/NEJMoa2115304
DO - 10.1056/NEJMoa2115304
M3 - Article
C2 - 34904799
AN - SCOPUS:85123295133
SN - 0028-4793
VL - 386
SP - 351
EP - 363
JO - New England Journal of Medicine
JF - New England Journal of Medicine
IS - 4
ER -