Relative Stability Of Plasma Cells Immunophenotype In Multiple Myeloma Over Time

Emerging evidence indicates that multiple myeloma (MM) can follow a number of evolutionary pathways over a patient’s disease course. Recently, genomic data have shown the coexistence in many patients of several tumour types, which could be either genetically stable, evolving linearly or be constituted of heterogeneous clonal mixtures with predominant clones shifting over time (Keats, Blood 2012;120:1067-1076). Little is known however of immunophenotypic evolution of the myeloma cells (MM cells) during MM progression.

In a retrospective single-centre analysis of tumoral immunophenotypes, we examined sequential bone marrow or peripheral blood samples from 51 MM patients. Multiparameter flow cytometry was performed to assess MM phenotype using CD38 and CD138 expression as well as intracytoplasmic light chain usage restriction in most cases. The presence or absence of CD19, CD20, CD27, CD28, CD56 or CD117 on the MM cells’surface was investigated additionally. A median of 4 of the latter antigens was examined per sample. Most MM cells were homogeneous in the expression or absence of expression of the differentiation antigens investigated. Immunophenotype changes were defined as the loss or gain of at least 1 antigen. Whenever partial expression of one or several antigens was observed on MM cells, indicating MM subsets, the presence of subclones was suspected.

Samples were obtained at diagnosis and relapse for 33 MM patients, and during consecutive relapses for 18. The total amount of analysed samples was 109, with a median of 2 samples per patient (range: 2-3). A modification of immunophenotype occurred in 22 patients (43%), with one antigen change (68%), two antigens changes (18%) or three antigens changes (14%). Immunophenotypic changes are summarized in table 1. For 20% of the cases or more, this involved CD28 (n=11, balanced gain or loss) or CD27 (n=7, mostly loss). CD56 expression, scarcely negative on the first assessment, was gained at relapse in three cases. Other antigens were expressed in a stable fashion over time. Eighteen (35%) of the patients had at least a subclone on the first immunophenotype, which was lost and/or modified in 14 / 18 patients at time of subsequent relapse.

There was no significant impact of immunophenotypic modifications on overall survival rates Similarly, the presence of a subclone at first examination, or the immunophenotypic change of this subclone over time was not associated with differences in overall survival rates.

In conclusion, this retrospective single centre study demonstrates that the immunophenotype of MM cells is mostly stable during the course of the disease. When changes occur, they do not seem to affect the clinical course of the patients. These preliminary results need confirmation on a larger and prospective trial.

No relevant conflicts of interest to declare.