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Addition of Lenalidomide to R-CHOP Improves Outcomes in Newly Diagnosed Diffuse Large B-Cell Lymphoma in a Randomized Phase II US Intergroup Study ECOG-ACRIN E1412

Lenalidomide combined with rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) (R2CHOP) in untreated diffuse large B-cell lymphoma (DLBCL) has shown promising activity, particularly in the activated B-cell–like (ABC) subtype. Eastern Cooperative Oncology Group (ECOG)-A...

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Autores principales: Nowakowski, Grzegorz S., Hong, Fangxin, Scott, David W., Macon, William R., King, Rebecca L., Habermann, Thomas M., Wagner-Johnston, Nina, Casulo, Carla, Wade, James L., Nagargoje, Gauri G., Reynolds, C. M., Cohen, Jonathon B., Khan, Nadia, Amengual, Jennifer E., Richards, Kristy L., Little, R. F., Leonard, John P., Friedberg, Jonathan W., Kostakoglu, Lale, Kahl, Brad S., Witzig, Thomas E.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Wolters Kluwer Health 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8078264/
https://www.ncbi.nlm.nih.gov/pubmed/33555941
http://dx.doi.org/10.1200/JCO.20.01375
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author Nowakowski, Grzegorz S.
Hong, Fangxin
Scott, David W.
Macon, William R.
King, Rebecca L.
Habermann, Thomas M.
Wagner-Johnston, Nina
Casulo, Carla
Wade, James L.
Nagargoje, Gauri G.
Reynolds, C. M.
Cohen, Jonathon B.
Khan, Nadia
Amengual, Jennifer E.
Richards, Kristy L.
Little, R. F.
Leonard, John P.
Friedberg, Jonathan W.
Kostakoglu, Lale
Kahl, Brad S.
Witzig, Thomas E.
author_facet Nowakowski, Grzegorz S.
Hong, Fangxin
Scott, David W.
Macon, William R.
King, Rebecca L.
Habermann, Thomas M.
Wagner-Johnston, Nina
Casulo, Carla
Wade, James L.
Nagargoje, Gauri G.
Reynolds, C. M.
Cohen, Jonathon B.
Khan, Nadia
Amengual, Jennifer E.
Richards, Kristy L.
Little, R. F.
Leonard, John P.
Friedberg, Jonathan W.
Kostakoglu, Lale
Kahl, Brad S.
Witzig, Thomas E.
author_sort Nowakowski, Grzegorz S.
collection PubMed
description Lenalidomide combined with rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) (R2CHOP) in untreated diffuse large B-cell lymphoma (DLBCL) has shown promising activity, particularly in the activated B-cell–like (ABC) subtype. Eastern Cooperative Oncology Group (ECOG)-ACRIN trial E1412 was a randomized phase II study comparing R2CHOP versus R-CHOP in untreated DLBCL. PATIENTS AND METHODS: Patients with newly diagnosed DLBCL, stage II bulky-IV disease, International Prognostic Index (IPI) ≥ 2, and ECOG performance status ≤ 2 were eligible and randomly assigned 1:1 to R2CHOP versus R-CHOP for six cycles. Tumors were analyzed using the NanoString Lymph2Cx for cell of origin. The primary end point was progression-free survival (PFS) in all patients with the co-primary end point of PFS in ABC-DLBCL. Secondary end points included overall response rate (ORR), complete response (CR) rate, and overall survival (OS). RESULTS: Three hundred forty-nine patients were enrolled; 280 patients (145 R2CHOP and 135 R-CHOP) were evaluable: 94 were ABC-DLBCL, 122 germinal center B-cell–like-DLBCL, 18 unclassifiable, and 46 unknowns. Baseline characteristics were well-balanced between arms, and the median age was 66 (range, 24-92); 70% of patients had stage IV disease; 34%, 43%, and 24% had IPI 2, 3, and 4 or 5, respectively. Myelosuppression was more common in the R2CHOP arm. The ORR and CR rate were 92% and 68% in R-CHOP and 97% (P = .06) and 73% (P = .43) in the R2CHOP arm, respectively. The median follow-up was 3.0 years; R2CHOP was associated with a 34% reduction in risk of progression or death versus R-CHOP (hazard ratio [HR], 0.66 95% CI, 0.43 to 1.01) and 3-year PFS of 73% versus 61%, one-sided P = .03, and an improvement in OS (83% and 75% at 3 years; HR, 0.67; one-sided P = .05). The PFS HR for R2CHOP was 0.67 for ABC-DLBCL, one-sided P = .1. CONCLUSION: In this signal-seeking study, the addition of lenalidomide to R-CHOP (R2CHOP) improved outcomes in newly diagnosed DLBCL including patients with ABC-DLBCL.
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spelling pubmed-80782642022-04-20 Addition of Lenalidomide to R-CHOP Improves Outcomes in Newly Diagnosed Diffuse Large B-Cell Lymphoma in a Randomized Phase II US Intergroup Study ECOG-ACRIN E1412 Nowakowski, Grzegorz S. Hong, Fangxin Scott, David W. Macon, William R. King, Rebecca L. Habermann, Thomas M. Wagner-Johnston, Nina Casulo, Carla Wade, James L. Nagargoje, Gauri G. Reynolds, C. M. Cohen, Jonathon B. Khan, Nadia Amengual, Jennifer E. Richards, Kristy L. Little, R. F. Leonard, John P. Friedberg, Jonathan W. Kostakoglu, Lale Kahl, Brad S. Witzig, Thomas E. J Clin Oncol ORIGINAL REPORTS Lenalidomide combined with rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) (R2CHOP) in untreated diffuse large B-cell lymphoma (DLBCL) has shown promising activity, particularly in the activated B-cell–like (ABC) subtype. Eastern Cooperative Oncology Group (ECOG)-ACRIN trial E1412 was a randomized phase II study comparing R2CHOP versus R-CHOP in untreated DLBCL. PATIENTS AND METHODS: Patients with newly diagnosed DLBCL, stage II bulky-IV disease, International Prognostic Index (IPI) ≥ 2, and ECOG performance status ≤ 2 were eligible and randomly assigned 1:1 to R2CHOP versus R-CHOP for six cycles. Tumors were analyzed using the NanoString Lymph2Cx for cell of origin. The primary end point was progression-free survival (PFS) in all patients with the co-primary end point of PFS in ABC-DLBCL. Secondary end points included overall response rate (ORR), complete response (CR) rate, and overall survival (OS). RESULTS: Three hundred forty-nine patients were enrolled; 280 patients (145 R2CHOP and 135 R-CHOP) were evaluable: 94 were ABC-DLBCL, 122 germinal center B-cell–like-DLBCL, 18 unclassifiable, and 46 unknowns. Baseline characteristics were well-balanced between arms, and the median age was 66 (range, 24-92); 70% of patients had stage IV disease; 34%, 43%, and 24% had IPI 2, 3, and 4 or 5, respectively. Myelosuppression was more common in the R2CHOP arm. The ORR and CR rate were 92% and 68% in R-CHOP and 97% (P = .06) and 73% (P = .43) in the R2CHOP arm, respectively. The median follow-up was 3.0 years; R2CHOP was associated with a 34% reduction in risk of progression or death versus R-CHOP (hazard ratio [HR], 0.66 95% CI, 0.43 to 1.01) and 3-year PFS of 73% versus 61%, one-sided P = .03, and an improvement in OS (83% and 75% at 3 years; HR, 0.67; one-sided P = .05). The PFS HR for R2CHOP was 0.67 for ABC-DLBCL, one-sided P = .1. CONCLUSION: In this signal-seeking study, the addition of lenalidomide to R-CHOP (R2CHOP) improved outcomes in newly diagnosed DLBCL including patients with ABC-DLBCL. Wolters Kluwer Health 2021-04-20 2021-02-08 /pmc/articles/PMC8078264/ /pubmed/33555941 http://dx.doi.org/10.1200/JCO.20.01375 Text en © 2021 by American Society of Clinical Oncology https://creativecommons.org/licenses/by-nc-nd/4.0/Creative Commons Attribution Non-Commercial No Derivatives 4.0 License: https://creativecommons.org/licenses/by-nc-nd/4.0/
spellingShingle ORIGINAL REPORTS
Nowakowski, Grzegorz S.
Hong, Fangxin
Scott, David W.
Macon, William R.
King, Rebecca L.
Habermann, Thomas M.
Wagner-Johnston, Nina
Casulo, Carla
Wade, James L.
Nagargoje, Gauri G.
Reynolds, C. M.
Cohen, Jonathon B.
Khan, Nadia
Amengual, Jennifer E.
Richards, Kristy L.
Little, R. F.
Leonard, John P.
Friedberg, Jonathan W.
Kostakoglu, Lale
Kahl, Brad S.
Witzig, Thomas E.
Addition of Lenalidomide to R-CHOP Improves Outcomes in Newly Diagnosed Diffuse Large B-Cell Lymphoma in a Randomized Phase II US Intergroup Study ECOG-ACRIN E1412
title Addition of Lenalidomide to R-CHOP Improves Outcomes in Newly Diagnosed Diffuse Large B-Cell Lymphoma in a Randomized Phase II US Intergroup Study ECOG-ACRIN E1412
title_full Addition of Lenalidomide to R-CHOP Improves Outcomes in Newly Diagnosed Diffuse Large B-Cell Lymphoma in a Randomized Phase II US Intergroup Study ECOG-ACRIN E1412
title_fullStr Addition of Lenalidomide to R-CHOP Improves Outcomes in Newly Diagnosed Diffuse Large B-Cell Lymphoma in a Randomized Phase II US Intergroup Study ECOG-ACRIN E1412
title_full_unstemmed Addition of Lenalidomide to R-CHOP Improves Outcomes in Newly Diagnosed Diffuse Large B-Cell Lymphoma in a Randomized Phase II US Intergroup Study ECOG-ACRIN E1412
title_short Addition of Lenalidomide to R-CHOP Improves Outcomes in Newly Diagnosed Diffuse Large B-Cell Lymphoma in a Randomized Phase II US Intergroup Study ECOG-ACRIN E1412
title_sort addition of lenalidomide to r-chop improves outcomes in newly diagnosed diffuse large b-cell lymphoma in a randomized phase ii us intergroup study ecog-acrin e1412
topic ORIGINAL REPORTS
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8078264/
https://www.ncbi.nlm.nih.gov/pubmed/33555941
http://dx.doi.org/10.1200/JCO.20.01375
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