Prognostic Value of Immunophenotyping of Multiple Myeloma: A Study on 685 Patients Uniformly Treated with High-Dose Therapy.

Analysis of the antigenic profile of malignant cells has shown to be a valuable tool for the diagnosis and the identification of prognostic markers in haematological malignancies. By contrast, in multiple myeloma (MM), immunophenotyping is rarely used in clinical practice. Moreover, conflicting results have been reported probably because they were based on short series of heterogeneously treated MM patients. In the present study, we have prospectively analysed the prognostic impact of antigenic markers, assessed by multiparametric flow cytometry, in a series of 685 newly diagnosed MM patients that were uniformly treated according to the GEM-2000 protocol. The results show that three antigenic markers (CD19, CD28 and CD117) afford prognostic information. The expression of both CD19 and CD28 as well as the absence of CD117 were associated with a significantly shorter progression free-survival (PFS) and overall survival (OS). Interestingly, the CD28 expression correlated with t(14;16) and Del(17p), while CD117 negative cases were associated with t(4;14) and Del(13q) as well as several other disease characteristics. The simultaneous assessment of CD28 and CD117 antigens, allowed stratification of myeloma patients into three risk categories:

• poor risk (CD28+CD117−),

• intermediate (either both markers negative or both positive), and

• good risk (CD28−CD117+), with PFS rates of 30, 37 and 45 months, respectively (p=0.01), and OS of 45, 68 and not reached, respectively (p=0.0001).

To the best of our knowledge, this is the first prospective analysis in which the prognostic impact of a relatively high number of antigenic markers has been simultaneously analysed in a large series of uniformly treated patients.