Multiple myeloma staging based on the combination of beta-2-microglobulin and albumin: the role of albumin in the model.

Background And Objective: Since the prognostic significance of the combination of beta-2-microglobulin (beta(2)m) and albumin in multiple myeloma (MM) has been recognized, these two easily obtainable parameters were subsequently employed in the staging systems of Bataille et al. (BSS), the South West Oncology Group (SWOG SS) and most recently the International Myeloma Working Group (ISS). There is no consensus, however, regarding the cut off levels of beta(2)m and the stage, early or advanced, at which albumin should be added to the model. At the same time, Weber et al. demonstrated similar results using beta(2)m alone in identical cut-offs with ISS (WSS). The aim of the present study is to apply these four staging systems in 504 MM patients, in order to discern the role of albumin in MM staging and evaluate if, and at which stage, albumin should be added to the model.

Methods: Median overall survival (OS) according to BSS, SWOG SS, ISS and WSS was estimated according to the Kaplan-Meier method. OS differences between the stages were assessed using the log-rank test. Patients with beta(2)m < 3.5 mg/l and albumin < 3.5 g/dl, who were classified in stage II according to ISS and in stage I according to WSS, were analyzed separately in order to detect in which prognostic group they practically belong.

Results: BSS and SWOG SS failed to distinguish stage II from stage III patients and stage III from stage IV patients, respectively. ISS and WSS achieved clear stratification of the patients into three distinct prognostic subgroups, but WSS I patients had a lower life expectancy than ISS I patients. This difference was due to false inclusion of patients with beta(2)m < 3.5 mg/l and albumin < 3.5 g/dl in stage I by WSS, while separate analysis of these patients proved that they belong, in fact, in stage II. In an attempt to improve its prognostic impact, WSS was then successfully modified by dividing WSS I patients in two substages, WSS IA: beta(2)m < 2.5 mg/l and WSS IB: 2.5 mg/l < or = beta(2)m < 3.5 mg/l, thus designating a low-risk and a low-intermediate-risk subgroup, respectively.

Conclusion: Albumin appears to lose its prognostic value at high cut-off levels of beta(2)m, while it enhances the prognostic significance of beta(2)m at low cut-off levels of the latter. Albumin cannot be eliminated from the ISS, since it is absolutely necessary in order to identify true low-risk patients. The only possibility for albumin exclusion from the model, could be to decrease the beta(2)m low-risk cut-off from 3.5 to 2.5 mg/l.