Revisiting Beta-2 Microglobulin As a Prognostic Marker in Diffuse Large B-cell Lymphoma

Background: Several clinical prognostic models for diffuse large B-cell lymphoma (DLBCL) have been proposed, including the most commonly used International Prognostic Index (IPI), the National Comprehensive Cancer Network IPI (NCCN-IPI), and models incorporating beta-2 microglobulin (beta 2M). However, the role of beta 2M in DLBCL patients is not fully understood. Methods: We identified 6075 patients with newly diagnosed DLBCL treated with immunochemotherapy registered in the Danish Lymphoma Registry. Results: A total of 3232 patients had data available to calculate risk scores from each of the nine considered risk models for DLBCL, including a model developed from our population. Three of four models with beta 2M and NCCN-IPI performed better than the International Prognostic Indexes (IPI, age-adjusted IPI, and revised IPI). Five-year overall survival for high- and low-risk patients were 43.6% and 86.4% for IPI and 34.9% and 96.2% for NCCN-IPI. In univariate analysis, higher levels of beta 2M were associated with inferior survival, higher tumor burden (advanced clinical stage and bulky disease), previous malignancy and increased age, and creatinine levels. Furthermore, we developed a model (beta 2M-NCCN-IPI) by adding beta 2M to NCCN-IPI (c-index 0.708) with improved discriminatory ability compared to NCCN-IPI (c-index 0.698, p < 0.05) and 5-year OS of 33.1%, 56.2%, 82.4%, and 96.4% in the high, high-intermediate, low-intermediate and low-risk group, respectively. Conclusion: International Prognostic Indices, except for NCCN-IPI, fail to accurately discriminate risk groups in the rituximab era. beta 2M, a readily available marker, could improve the discriminatory performance of NCCN-IPI and should be re-evaluated in the development setting of future models for DLBCL.