Lenalidomide combined with R-CHOP overcomes negative prognostic impact of non-germinal center B-cell phenotype in newly diagnosed diffuse large B-cell lymphoma: A phase II study

Grzegorz S Nowakowski, Betsy LaPlant, William R. Macon, Craig B. Reeder, James M Foran, Garth D. Nelson, Carrie A Thompson, Candido E Rivera, David J. Inwards, Ivana Micallef, Patrick Bruce Johnston, Luis F. Porrata, Stephen Maxted Ansell, Randy D. Gascoyne, Thomas Matthew Habermann, Thomas Elmer Witzig

Research output: Contribution to journalArticle

194 Citations (Scopus)

Abstract

Purpose: Lenalidomide has significant single-agent activity in relapsed diffuse large B-cell lymphoma (DLBCL). We demonstrated that lenalidomide can be safely combined with R-CHOP (rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone); this new combination is known as R2CHOP. The goal of this phase II study was to evaluate the efficacy of this combination in newly diagnosed DLBCL. Patients and Methods: Eligible patients were adults with newly diagnosed untreated stages II to IV CD20+ DLBCL. Patients received lenalidomide 25 mg orally per day on days 1 through 10 with standard-dose R-CHOP every 21 days for six cycles. All patients received pegfilgrastim on day 2 of each cycle and aspirin prophylaxis throughout. DLBCL molecular subtype was determined by tumor immunohistochemistry and classified as germinal center B-cell (GCB) versus non-GCB in the R2CHOP patients and 87 control patients with DLBCL from the Lymphoma Database who were treated with conventional R-CHOP. Results: In all, 64 patients with DLBCL were enrolled, and 60 were evaluable for response. The overall response rate was 98% (59 of 60) with 80% (48 of 60) achieving complete response. Event-free survival and overall survival (OS) rates at 24 months were 59% (95% CI, 48% to 74%) and 78% (95% CI, 68% to 90%), respectively. In R-CHOP patients, 24-month progression-free survival (PFS) and OS were 28% versus 64% (P < .001) and 46% versus 78% (P < .001) in non-GCB DLBCL versus GCB DLBCL, respectively. In contrast, there was no difference in 24-month PFS or OS for R2CHOP patients on the basis of non-GCB and GCB subtype (60% v 59% [P = .83] and 83% v 75% [P = .61] at 2 years, respectively). Conclusion: R2CHOP shows promising efficacy in DLBCL. The addition of lenalidomide appears to mitigate a negative impact of non-GCB phenotype on patient outcome.

Original languageEnglish (US)
Pages (from-to)251-257
Number of pages7
JournalJournal of Clinical Oncology
Volume33
Issue number3
DOIs
StatePublished - Jan 20 2015

Fingerprint

Lymphoma, Large B-Cell, Diffuse
B-Lymphocytes
Phenotype
Germinal Center
Disease-Free Survival
lenalidomide
Survival
Vincristine
Prednisone
Doxorubicin
Cyclophosphamide
Aspirin
Lymphoma
Survival Rate
Immunohistochemistry
Databases

ASJC Scopus subject areas

  • Cancer Research
  • Oncology
  • Medicine(all)

Cite this

@article{2901c9d7c86e47c188ac385c3c186a6c,
title = "Lenalidomide combined with R-CHOP overcomes negative prognostic impact of non-germinal center B-cell phenotype in newly diagnosed diffuse large B-cell lymphoma: A phase II study",
abstract = "Purpose: Lenalidomide has significant single-agent activity in relapsed diffuse large B-cell lymphoma (DLBCL). We demonstrated that lenalidomide can be safely combined with R-CHOP (rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone); this new combination is known as R2CHOP. The goal of this phase II study was to evaluate the efficacy of this combination in newly diagnosed DLBCL. Patients and Methods: Eligible patients were adults with newly diagnosed untreated stages II to IV CD20+ DLBCL. Patients received lenalidomide 25 mg orally per day on days 1 through 10 with standard-dose R-CHOP every 21 days for six cycles. All patients received pegfilgrastim on day 2 of each cycle and aspirin prophylaxis throughout. DLBCL molecular subtype was determined by tumor immunohistochemistry and classified as germinal center B-cell (GCB) versus non-GCB in the R2CHOP patients and 87 control patients with DLBCL from the Lymphoma Database who were treated with conventional R-CHOP. Results: In all, 64 patients with DLBCL were enrolled, and 60 were evaluable for response. The overall response rate was 98{\%} (59 of 60) with 80{\%} (48 of 60) achieving complete response. Event-free survival and overall survival (OS) rates at 24 months were 59{\%} (95{\%} CI, 48{\%} to 74{\%}) and 78{\%} (95{\%} CI, 68{\%} to 90{\%}), respectively. In R-CHOP patients, 24-month progression-free survival (PFS) and OS were 28{\%} versus 64{\%} (P < .001) and 46{\%} versus 78{\%} (P < .001) in non-GCB DLBCL versus GCB DLBCL, respectively. In contrast, there was no difference in 24-month PFS or OS for R2CHOP patients on the basis of non-GCB and GCB subtype (60{\%} v 59{\%} [P = .83] and 83{\%} v 75{\%} [P = .61] at 2 years, respectively). Conclusion: R2CHOP shows promising efficacy in DLBCL. The addition of lenalidomide appears to mitigate a negative impact of non-GCB phenotype on patient outcome.",
author = "Nowakowski, {Grzegorz S} and Betsy LaPlant and Macon, {William R.} and Reeder, {Craig B.} and Foran, {James M} and Nelson, {Garth D.} and Thompson, {Carrie A} and Rivera, {Candido E} and Inwards, {David J.} and Ivana Micallef and Johnston, {Patrick Bruce} and Porrata, {Luis F.} and Ansell, {Stephen Maxted} and Gascoyne, {Randy D.} and Habermann, {Thomas Matthew} and Witzig, {Thomas Elmer}",
year = "2015",
month = "1",
day = "20",
doi = "10.1200/JCO.2014.55.5714",
language = "English (US)",
volume = "33",
pages = "251--257",
journal = "Journal of Clinical Oncology",
issn = "0732-183X",
publisher = "American Society of Clinical Oncology",
number = "3",

}

TY - JOUR

T1 - Lenalidomide combined with R-CHOP overcomes negative prognostic impact of non-germinal center B-cell phenotype in newly diagnosed diffuse large B-cell lymphoma

T2 - A phase II study

AU - Nowakowski, Grzegorz S

AU - LaPlant, Betsy

AU - Macon, William R.

AU - Reeder, Craig B.

AU - Foran, James M

AU - Nelson, Garth D.

AU - Thompson, Carrie A

AU - Rivera, Candido E

AU - Inwards, David J.

AU - Micallef, Ivana

AU - Johnston, Patrick Bruce

AU - Porrata, Luis F.

AU - Ansell, Stephen Maxted

AU - Gascoyne, Randy D.

AU - Habermann, Thomas Matthew

AU - Witzig, Thomas Elmer

PY - 2015/1/20

Y1 - 2015/1/20

N2 - Purpose: Lenalidomide has significant single-agent activity in relapsed diffuse large B-cell lymphoma (DLBCL). We demonstrated that lenalidomide can be safely combined with R-CHOP (rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone); this new combination is known as R2CHOP. The goal of this phase II study was to evaluate the efficacy of this combination in newly diagnosed DLBCL. Patients and Methods: Eligible patients were adults with newly diagnosed untreated stages II to IV CD20+ DLBCL. Patients received lenalidomide 25 mg orally per day on days 1 through 10 with standard-dose R-CHOP every 21 days for six cycles. All patients received pegfilgrastim on day 2 of each cycle and aspirin prophylaxis throughout. DLBCL molecular subtype was determined by tumor immunohistochemistry and classified as germinal center B-cell (GCB) versus non-GCB in the R2CHOP patients and 87 control patients with DLBCL from the Lymphoma Database who were treated with conventional R-CHOP. Results: In all, 64 patients with DLBCL were enrolled, and 60 were evaluable for response. The overall response rate was 98% (59 of 60) with 80% (48 of 60) achieving complete response. Event-free survival and overall survival (OS) rates at 24 months were 59% (95% CI, 48% to 74%) and 78% (95% CI, 68% to 90%), respectively. In R-CHOP patients, 24-month progression-free survival (PFS) and OS were 28% versus 64% (P < .001) and 46% versus 78% (P < .001) in non-GCB DLBCL versus GCB DLBCL, respectively. In contrast, there was no difference in 24-month PFS or OS for R2CHOP patients on the basis of non-GCB and GCB subtype (60% v 59% [P = .83] and 83% v 75% [P = .61] at 2 years, respectively). Conclusion: R2CHOP shows promising efficacy in DLBCL. The addition of lenalidomide appears to mitigate a negative impact of non-GCB phenotype on patient outcome.

AB - Purpose: Lenalidomide has significant single-agent activity in relapsed diffuse large B-cell lymphoma (DLBCL). We demonstrated that lenalidomide can be safely combined with R-CHOP (rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone); this new combination is known as R2CHOP. The goal of this phase II study was to evaluate the efficacy of this combination in newly diagnosed DLBCL. Patients and Methods: Eligible patients were adults with newly diagnosed untreated stages II to IV CD20+ DLBCL. Patients received lenalidomide 25 mg orally per day on days 1 through 10 with standard-dose R-CHOP every 21 days for six cycles. All patients received pegfilgrastim on day 2 of each cycle and aspirin prophylaxis throughout. DLBCL molecular subtype was determined by tumor immunohistochemistry and classified as germinal center B-cell (GCB) versus non-GCB in the R2CHOP patients and 87 control patients with DLBCL from the Lymphoma Database who were treated with conventional R-CHOP. Results: In all, 64 patients with DLBCL were enrolled, and 60 were evaluable for response. The overall response rate was 98% (59 of 60) with 80% (48 of 60) achieving complete response. Event-free survival and overall survival (OS) rates at 24 months were 59% (95% CI, 48% to 74%) and 78% (95% CI, 68% to 90%), respectively. In R-CHOP patients, 24-month progression-free survival (PFS) and OS were 28% versus 64% (P < .001) and 46% versus 78% (P < .001) in non-GCB DLBCL versus GCB DLBCL, respectively. In contrast, there was no difference in 24-month PFS or OS for R2CHOP patients on the basis of non-GCB and GCB subtype (60% v 59% [P = .83] and 83% v 75% [P = .61] at 2 years, respectively). Conclusion: R2CHOP shows promising efficacy in DLBCL. The addition of lenalidomide appears to mitigate a negative impact of non-GCB phenotype on patient outcome.

UR - http://www.scopus.com/inward/record.url?scp=84921764017&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84921764017&partnerID=8YFLogxK

U2 - 10.1200/JCO.2014.55.5714

DO - 10.1200/JCO.2014.55.5714

M3 - Article

C2 - 25135992

AN - SCOPUS:84921764017

VL - 33

SP - 251

EP - 257

JO - Journal of Clinical Oncology

JF - Journal of Clinical Oncology

SN - 0732-183X

IS - 3

ER -