Addition of Rituximab to Standard Chemotherapy Improves the Survival of Both the Germinal Center B-Cell-Like and Non-Germinal Center B-Cell-Like Subtypes of Diffuse Large B-Cell Lymphoma

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Journal of Clinical Oncology, 10.1200/JCO.2007.15.9277

Addition of Rituximab to Standard Chemotherapy Improves the Survival of Both the

Germinal Center B-Cell-Like and Non-Germinal Center B-Cell-Like Subtypes of

Diffuse Large B-Cell Lymphoma

Kai Fu, Dennis D. Weisenburger, W.L. Choi, D. , Lynette M.

, Xinlan Shi, P. Hans, C. Greiner, Philip J. Bierman, R.

Bociek, O. Armitage, Wing C. Chan, and M. Vose*

From the Departments of Pathology and Microbiology, Biostatistics, and Internal

Medicine, University of Nebraska Medical Center, Omaha, NE.

* To whom correspondence should be addressed. E-mail: jmvose@...

Purpose: Diffuse large B-cell lymphoma (DLBCL) includes at least two

prognostically important subtypes (ie, germinal center B-cell-like [GCB] and

activated B-cell-like [ABC] DLBCL), which initially were characterized by gene

expression profiling and subsequently were confirmed by immunostaining. However,

with the addition of rituximab to standard chemotherapy, the prognostic

significance of this subclassification of DLBCL is unclear.

Patients and Methods: We studied 243 patient cases of de novo DLBCL, which

included 131 patient cases treated with rituximab plus standard chemotherapy

(rituximab group) and 112 patient cases treated with only standard chemotherapy

(control group). The cases were assigned to GCB or non-GCB subgroups (the latter

of which included both ABC DLBCL and unclassifiable DLBCL) on the basis of

immunophenotype by using the Hans method. Clinical characteristics and survival

outcomes of the two patient groups were compared.

Results: The clinical characteristics of the patients in the rituximab and the

control groups were similar. Compared with the control group, addition of

rituximab improved the 3-year overall survival (OS; 42% v 77%; P < .001) of

patients with DLBCL. Rituximab-treated patients in either the GCB or the non-GCB

subgroups also had a significantly improved 3-year OS compared with their

respective subgroups in the control group (P < .001). In the rituximab group,

the GCB subgroup had a significantly better 3-year OS than the non-GCB subgroup

(85% v 69%; P = .032). Multivariate analyses confirmed that rituximab treatment

was predictive for survival in both the GCB and the non-GCB subgroups.

Conclusion: In this retrospective study, we have shown that the

subclassification of DLBCL on the basis of the cell of origin continues to have

prognostic importance in the rituximab era.