Expression of p21 protein predicts clinical outcome in DLBCL patients older than 60 years treated with R-CHOP but not CHOP: a prospective ECOG and Southwest Oncology Group correlative study on E4494.

Abstract

PURPOSE:

To prospectively investigate the prognostic significance of p21 and p53 expression in diffuse large B-cell lymphoma in the context of the U.S. Intergroup trial comparing conventional cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP) chemotherapy to rituximab-CHOP (R-CHOP) induction, with or without maintenance rituximab.

EXPERIMENTAL DESIGN:

Immunohistochemical staining of 197 paraffin-embedded biopsy specimens was scored by an independent panel of experts.

RESULTS:

The cyclin-dependent kinase inhibitor, p21, was expressed in 55% of cases examined. In a multivariable analysis adjusting for International Prognostic Index score and BCL2 status, p21 expression was a significant, independent, favorable predictive factor for failure-free survival (relative risk, 0.3; P = 0.001) and overall survival (relative risk, 0.3; P = 0.003) for patients treated with R-CHOP. Expression of p21 was not predictive of outcome for CHOP-treated patients. Only p21-positive cases benefited from the addition of rituximab to CHOP. Among p21-positive patients, treatment with R-CHOP was associated with a higher failure-free survival rate at 5 years compared with CHOP (61% versus 24%; P = 0.01). In contrast, no significant differences were detected in failure-free survival according to treatment arm for p21-negative patients. Expression of p53, alone or in combination with p21, did not predict for outcome in univariable or multivariable analyses.

CONCLUSIONS:

In this study, p21 protein expression emerged as an important independent predictor of a favorable clinical outcome when rituximab was added to CHOP therapy. These data suggest that rituximab-related effects on lymphoma survival pathways may be functionally linked to p21 activity.

• Authors: Jane N Winter, Shuli Li, Vikas Aurora, Daina Variakojis, Beverly Nelson, Maryla Krajewska, Lijun Zhang, Thomas M Habermann, Richard I Fisher, William R Macon, Mukesh Chhanabhai, Raymond E Felgar, Eric D Hsi, L Jeffrey Medeiros, James K Weick, Edie A Weller, Ari Melnick, John C Reed, Sandra J Horning, Randy D Gascoyne
• Journal: Clinical cancer research : an official journal of the American Association for Cancer Research (Clin Cancer Res) Vol. 16 Issue 8 Pg. 2435-42 (Apr 15 2010) ISSN: 1557-3265 [Electronic] United States
• PMID: 20371683 (Publication Type: Comparative Study, Journal Article, Randomized Controlled Trial, Research Support, N.I.H., Extramural)

Chemical References

• Antibodies, Monoclonal
• Antibodies, Monoclonal, Murine-Derived
• Biomarkers, Tumor
• CDKN1A protein, human
• Cyclin-Dependent Kinase Inhibitor p21
• Rituximab
• Vincristine
• Doxorubicin
• Cyclophosphamide
• Prednisone

Topics

• Age Factors
• Aged
• Aged, 80 and over
• Antibodies, Monoclonal (administration & dosage)
• Antibodies, Monoclonal, Murine-Derived
• Antineoplastic Combined Chemotherapy Protocols (therapeutic use)
• Biomarkers, Tumor (genetics, metabolism)
• Cyclin-Dependent Kinase Inhibitor p21 (metabolism)
• Cyclophosphamide (administration & dosage)
• Doxorubicin (administration & dosage)
• Female
• Humans
• Immunoenzyme Techniques
• Lymphoma, Large B-Cell, Diffuse (drug therapy, metabolism, pathology)
• Male
• Middle Aged
• Prednisone (administration & dosage)
• Rituximab
• Survival Rate
• Treatment Outcome
• Vincristine (administration & dosage)