Lenalidomide maintenance compared with placebo in responding elderly patients with diffuse large B-cell lymphoma treated with first-line rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone

Catherine Thieblemont, Hervé Tilly, Maria Gomes Da Silva, Rene Olivier Casasnovas, Christophe Fruchart, Franck Morschhauser, Corinne Haioun, Julien Lazarovici, Anida Grosicka, Aurore Perrot, Judith Trotman, Catherine Sebban, Dolores Caballero, Richard Greil, Koen Van Eygen, Amos M. Cohen, Hugo Gonzalez, Reda Bouabdallah, Lucie Oberic, Bernadette Corront & 10 others Bachra Choufi, Armando Lopez-Guillermo, John Catalano, Achiel Van Hoof, Josette Briere, Jose Cabeçadas, Gilles Salles, Philippe Gaulard, Andre Bosly, Bertrand B Coiffier

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Abstract

Purpose: The standard treatment of patients with diffuse large B-cell lymphoma (DLBCL) is rituximab in combination with cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP). Lenalidomide, an immunomodulatory agent, has shown activity in DLBCL. This randomized phase III trial compared lenalidomide as maintenance therapy with placebo in elderly patients with DLBCL who achieved a complete response (CR) or partial response (PR) to R-CHOP induction. Methods: Patients with previously untreated DLBCL or other aggressive B-cell lymphoma were 60 to 80 years old, had CR or PR after six or eight cycles of R-CHOP, and were randomly assigned to lenalidomide maintenance 25 mg/d or placebo for 21 days of every 28-day cycle for 24 months. The primary end point was progression-free survival (PFS). Results: A total of 650 patients were randomly assigned. At the time of the primary analysis (December 2015), with a median follow-up of 39 months from random assignment, median PFS was not reached for lenalidomide maintenance versus 58.9 months for placebo (hazard ratio, 0.708; 95% CI, 0.537 to 0.933; P = .01). The result was consistent among analyzed subgroups (eg, male v female, age-adjusted International Prognostic Index 0 or 1 v 2 or 3, age younger than 70 v ≥ 70 years), response (PR v CR) after R-CHOP, and positron emission tomography status at assignment (negative v positive). With longer median follow-up of 52 months (October 2016), overall survival was similar between arms (hazard ratio, 1.218; 95% CI, 0.861 to 1.721; P = .26). Most common grade 3 or 4 adverse events associated with lenalidomide versus placebo maintenance were neutropenia (56% v 22%) and cutaneous reactions (5% v 1%), respectively. Conclusion: Lenalidomide maintenance for 24 months after obtaining a CR or PR to R-CHOP significantly prolonged PFS in elderly patients with DLBCL.

Original languageEnglish
Pages (from-to)2473-2481
Number of pages9
JournalJournal of Clinical Oncology
Volume35
Issue number22
DOIs
Publication statusPublished - 1 Aug 2017

Cite this

Thieblemont, Catherine ; Tilly, Hervé ; Da Silva, Maria Gomes ; Casasnovas, Rene Olivier ; Fruchart, Christophe ; Morschhauser, Franck ; Haioun, Corinne ; Lazarovici, Julien ; Grosicka, Anida ; Perrot, Aurore ; Trotman, Judith ; Sebban, Catherine ; Caballero, Dolores ; Greil, Richard ; Van Eygen, Koen ; Cohen, Amos M. ; Gonzalez, Hugo ; Bouabdallah, Reda ; Oberic, Lucie ; Corront, Bernadette ; Choufi, Bachra ; Lopez-Guillermo, Armando ; Catalano, John ; Van Hoof, Achiel ; Briere, Josette ; Cabeçadas, Jose ; Salles, Gilles ; Gaulard, Philippe ; Bosly, Andre ; Coiffier, Bertrand B. / Lenalidomide maintenance compared with placebo in responding elderly patients with diffuse large B-cell lymphoma treated with first-line rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone. In: Journal of Clinical Oncology. 2017 ; Vol. 35, No. 22. pp. 2473-2481.
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title = "Lenalidomide maintenance compared with placebo in responding elderly patients with diffuse large B-cell lymphoma treated with first-line rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone",
abstract = "Purpose: The standard treatment of patients with diffuse large B-cell lymphoma (DLBCL) is rituximab in combination with cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP). Lenalidomide, an immunomodulatory agent, has shown activity in DLBCL. This randomized phase III trial compared lenalidomide as maintenance therapy with placebo in elderly patients with DLBCL who achieved a complete response (CR) or partial response (PR) to R-CHOP induction. Methods: Patients with previously untreated DLBCL or other aggressive B-cell lymphoma were 60 to 80 years old, had CR or PR after six or eight cycles of R-CHOP, and were randomly assigned to lenalidomide maintenance 25 mg/d or placebo for 21 days of every 28-day cycle for 24 months. The primary end point was progression-free survival (PFS). Results: A total of 650 patients were randomly assigned. At the time of the primary analysis (December 2015), with a median follow-up of 39 months from random assignment, median PFS was not reached for lenalidomide maintenance versus 58.9 months for placebo (hazard ratio, 0.708; 95{\%} CI, 0.537 to 0.933; P = .01). The result was consistent among analyzed subgroups (eg, male v female, age-adjusted International Prognostic Index 0 or 1 v 2 or 3, age younger than 70 v ≥ 70 years), response (PR v CR) after R-CHOP, and positron emission tomography status at assignment (negative v positive). With longer median follow-up of 52 months (October 2016), overall survival was similar between arms (hazard ratio, 1.218; 95{\%} CI, 0.861 to 1.721; P = .26). Most common grade 3 or 4 adverse events associated with lenalidomide versus placebo maintenance were neutropenia (56{\%} v 22{\%}) and cutaneous reactions (5{\%} v 1{\%}), respectively. Conclusion: Lenalidomide maintenance for 24 months after obtaining a CR or PR to R-CHOP significantly prolonged PFS in elderly patients with DLBCL.",
author = "Catherine Thieblemont and Herv{\'e} Tilly and {Da Silva}, {Maria Gomes} and Casasnovas, {Rene Olivier} and Christophe Fruchart and Franck Morschhauser and Corinne Haioun and Julien Lazarovici and Anida Grosicka and Aurore Perrot and Judith Trotman and Catherine Sebban and Dolores Caballero and Richard Greil and {Van Eygen}, Koen and Cohen, {Amos M.} and Hugo Gonzalez and Reda Bouabdallah and Lucie Oberic and Bernadette Corront and Bachra Choufi and Armando Lopez-Guillermo and John Catalano and {Van Hoof}, Achiel and Josette Briere and Jose Cabe{\cc}adas and Gilles Salles and Philippe Gaulard and Andre Bosly and Coiffier, {Bertrand B}",
year = "2017",
month = "8",
day = "1",
doi = "10.1200/JCO.2017.72.6984",
language = "English",
volume = "35",
pages = "2473--2481",
journal = "Journal of Clinical Oncology",
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publisher = "AMER SOC CLINICAL ONCOLOGY",
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Thieblemont, C, Tilly, H, Da Silva, MG, Casasnovas, RO, Fruchart, C, Morschhauser, F, Haioun, C, Lazarovici, J, Grosicka, A, Perrot, A, Trotman, J, Sebban, C, Caballero, D, Greil, R, Van Eygen, K, Cohen, AM, Gonzalez, H, Bouabdallah, R, Oberic, L, Corront, B, Choufi, B, Lopez-Guillermo, A, Catalano, J, Van Hoof, A, Briere, J, Cabeçadas, J, Salles, G, Gaulard, P, Bosly, A & Coiffier, BB 2017, 'Lenalidomide maintenance compared with placebo in responding elderly patients with diffuse large B-cell lymphoma treated with first-line rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone', Journal of Clinical Oncology, vol. 35, no. 22, pp. 2473-2481. https://doi.org/10.1200/JCO.2017.72.6984

Lenalidomide maintenance compared with placebo in responding elderly patients with diffuse large B-cell lymphoma treated with first-line rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone. / Thieblemont, Catherine; Tilly, Hervé; Da Silva, Maria Gomes; Casasnovas, Rene Olivier; Fruchart, Christophe; Morschhauser, Franck; Haioun, Corinne; Lazarovici, Julien; Grosicka, Anida; Perrot, Aurore; Trotman, Judith; Sebban, Catherine; Caballero, Dolores; Greil, Richard; Van Eygen, Koen; Cohen, Amos M.; Gonzalez, Hugo; Bouabdallah, Reda; Oberic, Lucie; Corront, Bernadette; Choufi, Bachra; Lopez-Guillermo, Armando; Catalano, John; Van Hoof, Achiel; Briere, Josette; Cabeçadas, Jose; Salles, Gilles; Gaulard, Philippe; Bosly, Andre; Coiffier, Bertrand B.

In: Journal of Clinical Oncology, Vol. 35, No. 22, 01.08.2017, p. 2473-2481.

Research output: Contribution to journalArticleResearchpeer-review

TY - JOUR

T1 - Lenalidomide maintenance compared with placebo in responding elderly patients with diffuse large B-cell lymphoma treated with first-line rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone

AU - Thieblemont, Catherine

AU - Tilly, Hervé

AU - Da Silva, Maria Gomes

AU - Casasnovas, Rene Olivier

AU - Fruchart, Christophe

AU - Morschhauser, Franck

AU - Haioun, Corinne

AU - Lazarovici, Julien

AU - Grosicka, Anida

AU - Perrot, Aurore

AU - Trotman, Judith

AU - Sebban, Catherine

AU - Caballero, Dolores

AU - Greil, Richard

AU - Van Eygen, Koen

AU - Cohen, Amos M.

AU - Gonzalez, Hugo

AU - Bouabdallah, Reda

AU - Oberic, Lucie

AU - Corront, Bernadette

AU - Choufi, Bachra

AU - Lopez-Guillermo, Armando

AU - Catalano, John

AU - Van Hoof, Achiel

AU - Briere, Josette

AU - Cabeçadas, Jose

AU - Salles, Gilles

AU - Gaulard, Philippe

AU - Bosly, Andre

AU - Coiffier, Bertrand B

PY - 2017/8/1

Y1 - 2017/8/1

N2 - Purpose: The standard treatment of patients with diffuse large B-cell lymphoma (DLBCL) is rituximab in combination with cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP). Lenalidomide, an immunomodulatory agent, has shown activity in DLBCL. This randomized phase III trial compared lenalidomide as maintenance therapy with placebo in elderly patients with DLBCL who achieved a complete response (CR) or partial response (PR) to R-CHOP induction. Methods: Patients with previously untreated DLBCL or other aggressive B-cell lymphoma were 60 to 80 years old, had CR or PR after six or eight cycles of R-CHOP, and were randomly assigned to lenalidomide maintenance 25 mg/d or placebo for 21 days of every 28-day cycle for 24 months. The primary end point was progression-free survival (PFS). Results: A total of 650 patients were randomly assigned. At the time of the primary analysis (December 2015), with a median follow-up of 39 months from random assignment, median PFS was not reached for lenalidomide maintenance versus 58.9 months for placebo (hazard ratio, 0.708; 95% CI, 0.537 to 0.933; P = .01). The result was consistent among analyzed subgroups (eg, male v female, age-adjusted International Prognostic Index 0 or 1 v 2 or 3, age younger than 70 v ≥ 70 years), response (PR v CR) after R-CHOP, and positron emission tomography status at assignment (negative v positive). With longer median follow-up of 52 months (October 2016), overall survival was similar between arms (hazard ratio, 1.218; 95% CI, 0.861 to 1.721; P = .26). Most common grade 3 or 4 adverse events associated with lenalidomide versus placebo maintenance were neutropenia (56% v 22%) and cutaneous reactions (5% v 1%), respectively. Conclusion: Lenalidomide maintenance for 24 months after obtaining a CR or PR to R-CHOP significantly prolonged PFS in elderly patients with DLBCL.

AB - Purpose: The standard treatment of patients with diffuse large B-cell lymphoma (DLBCL) is rituximab in combination with cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP). Lenalidomide, an immunomodulatory agent, has shown activity in DLBCL. This randomized phase III trial compared lenalidomide as maintenance therapy with placebo in elderly patients with DLBCL who achieved a complete response (CR) or partial response (PR) to R-CHOP induction. Methods: Patients with previously untreated DLBCL or other aggressive B-cell lymphoma were 60 to 80 years old, had CR or PR after six or eight cycles of R-CHOP, and were randomly assigned to lenalidomide maintenance 25 mg/d or placebo for 21 days of every 28-day cycle for 24 months. The primary end point was progression-free survival (PFS). Results: A total of 650 patients were randomly assigned. At the time of the primary analysis (December 2015), with a median follow-up of 39 months from random assignment, median PFS was not reached for lenalidomide maintenance versus 58.9 months for placebo (hazard ratio, 0.708; 95% CI, 0.537 to 0.933; P = .01). The result was consistent among analyzed subgroups (eg, male v female, age-adjusted International Prognostic Index 0 or 1 v 2 or 3, age younger than 70 v ≥ 70 years), response (PR v CR) after R-CHOP, and positron emission tomography status at assignment (negative v positive). With longer median follow-up of 52 months (October 2016), overall survival was similar between arms (hazard ratio, 1.218; 95% CI, 0.861 to 1.721; P = .26). Most common grade 3 or 4 adverse events associated with lenalidomide versus placebo maintenance were neutropenia (56% v 22%) and cutaneous reactions (5% v 1%), respectively. Conclusion: Lenalidomide maintenance for 24 months after obtaining a CR or PR to R-CHOP significantly prolonged PFS in elderly patients with DLBCL.

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U2 - 10.1200/JCO.2017.72.6984

DO - 10.1200/JCO.2017.72.6984

M3 - Article

VL - 35

SP - 2473

EP - 2481

JO - Journal of Clinical Oncology

JF - Journal of Clinical Oncology

SN - 0732-183X

IS - 22

ER -