Résumé
Multiple myeloma patients? survival under treatment varies from a few months
to more than 15 years. Clinical prognostic factors, especially
beta2-microglobulin (B2M) and the international staging system (ISS), allow
risk assessment to a certain extent, but do not identify patients at very
high risk. As malignant plasma cells are characterized by a variety of
chromosomal aberrations and changes in gene expression, a molecular
characterization of CD138-purified myeloma cells by interphase fluorescence
in situ hybridization (iFISH) and gene expression profiling (GEP) can be used
for improved risk assessment. iFISH allows a risk stratification with
presence of a translocation t(4;14) and/or deletion of 17p13 being the best
documented adverse prognostic factors. A deletion of 13q14 is no longer
considered to define adverse risk. Patients harbouring a t(4;14) seems to
benefit from a bortezomib- or lenalidomide containing regimen, whereas
patients with deletion 17p13 seem only to benefit from a high dose therapy
approach using long term bortezomib (in induction and maintenance) and
autologous tandem-transplantation as used in the GMMG-HD4 trial, or the total
therapy 3 concept. Gene expression profiling allows the assessment of high
risk scores (IFM, UAMS), remaining prognostic despite treatment with novel
agents, and prognostic surrogates of biological factors (e.g. proliferation)
and (prognostic) target gene expression (e.g. Aurora-kinase A). Thus,
assessment of B2M and ISS-stage, iFISH, and GEP is considered extended
routine diagnostics in therapy requiring multiple myeloma patients for risk
assessment and, even now, to a certain extent selection of treatment.
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