Polatuzumab Vedotin in Previously Untreated Diffuse Large B-Cell Lymphoma

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 M. Bergua-Burgués; Matthew C. Cheung; Antonio Pinto; Ho Jin Shin; Greg Hapgood; Eduardo Munhoz; Pau Abrisqueta; Jyh Pyng Gau; Jamie Hirata; Yanwen Jiang; Mark Yan; Calvin Lee; Christopher R. Flowers; Gilles Salles

doi:10.1056/NEJMoa2115304

Polatuzumab Vedotin in Previously Untreated Diffuse Large B-Cell Lymphoma

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 M. Bergua-Burgués
, Matthew C. Cheung

Antonio Pinto, Ho Jin Shin, Greg Hapgood, Eduardo Munhoz, Pau Abrisqueta, Jyh Pyng Gau, Jamie Hirata, Yanwen Jiang, Mark Yan, Calvin Lee, Christopher R. Flowers, Gilles Salles

Research output: Contribution to journal › Article › peer-review

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 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.

Original language	American English
Pages (from-to)	351-363
Number of pages	13
Journal	New England Journal of Medicine
Volume	386
Issue number	4
DOIs	https://doi.org/10.1056/NEJMoa2115304
State	Published - Jan 27 2022
Externally published	Yes

ASJC Scopus subject areas

General Medicine

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10.1056/NEJMoa2115304

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Tilly, H., Morschhauser, F., Sehn, L. H., Friedberg, J. W., Trněný, M., Sharman, J. P., Herbaux, C., Burke, J. M., Matasar, M., Rai, S., Izutsu, K., Mehta-Shah, N., Oberic, L., Chauchet, A., Jurczak, W., Song, Y., Greil, R., Mykhalska, L., Bergua-Burgués, J. M., ... Salles, G. (2022). Polatuzumab Vedotin in Previously Untreated Diffuse Large B-Cell Lymphoma. New England Journal of Medicine, 386(4), 351-363. https://doi.org/10.1056/NEJMoa2115304

@article{39688c55e00642f9b99ff394f3562308,

title = "Polatuzumab Vedotin in Previously Untreated Diffuse Large B-Cell Lymphoma",

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 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.",

author = "Herv{\'e} Tilly and Franck Morschhauser and Sehn, \{Laurie H.\} and Friedberg, \{Jonathan W.\} and Marek Trn{\v e}n{\'y} and Sharman, \{Jeff P.\} and Charles Herbaux and Burke, \{John M.\} and Matthew Matasar and Shinya Rai and Koji Izutsu and Neha Mehta-Shah and Lucie Oberic and Adrien Chauchet and Wojciech Jurczak and Yuqin Song and Richard Greil and Larysa Mykhalska and Bergua-Burgu{\'e}s, \{Juan M.\} and Cheung, \{Matthew C.\} and Antonio Pinto and Shin, \{Ho Jin\} and Greg Hapgood and Eduardo Munhoz and Pau Abrisqueta and Gau, \{Jyh Pyng\} and Jamie Hirata and Yanwen Jiang and Mark Yan and Calvin Lee and Flowers, \{Christopher R.\} and Gilles Salles",

note = "Publisher Copyright: Copyright {\textcopyright} 2021 Massachusetts Medical Society.",

year = "2022",

month = jan,

day = "27",

doi = "10.1056/NEJMoa2115304",

language = "American English",

volume = "386",

pages = "351--363",

journal = "New England Journal of Medicine",

issn = "0028-4793",

publisher = "Massachussetts Medical Society",

number = "4",

}

Tilly, H, Morschhauser, F, Sehn, LH, Friedberg, JW, Trněný, M, Sharman, JP, Herbaux, C, Burke, JM, Matasar, M, Rai, S, Izutsu, K, Mehta-Shah, N, Oberic, L, Chauchet, A, Jurczak, W, Song, Y, Greil, R, Mykhalska, L, Bergua-Burgués, JM, Cheung, MC, Pinto, A, Shin, HJ, Hapgood, G, Munhoz, E, Abrisqueta, P, Gau, JP, Hirata, J, Jiang, Y, Yan, M, Lee, C, Flowers, CR & Salles, G 2022, 'Polatuzumab Vedotin in Previously Untreated Diffuse Large B-Cell Lymphoma', New England Journal of Medicine, vol. 386, no. 4, pp. 351-363. https://doi.org/10.1056/NEJMoa2115304

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

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.

UR - https://www.scopus.com/pages/publications/85123295133

UR - https://www.scopus.com/pages/publications/85123295133#tab=citedBy

U2 - 10.1056/NEJMoa2115304

DO - 10.1056/NEJMoa2115304

M3 - Article

C2 - 34904799

SN - 0028-4793

VL - 386

SP - 351

EP - 363

JO - New England Journal of Medicine

JF - New England Journal of Medicine

IS - 4

ER -

Polatuzumab Vedotin in Previously Untreated Diffuse Large B-Cell Lymphoma

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