The Molecular Characterization of Multiple Myeloma at Relapse

Multiple myeloma (MM) is an incurable cancer. The disease can often be brought to a halt with chemotherapy which in younger patients is accompanied by stem cell transplantation. But the disease relapses almost invariably. Cytogenetic changes in the myeloma cells can serve as prognostic markers. Accordingly, 25% of the patients show changes associated with a prognosis so poor that they should probably receive experimental treatment right from the start. Nevertheless, a part of these patients survive much longer than expected. Thus, the prognosis must depend on additional genetic events.

The aim of this project is to widen the investigators knowledge of the nature, chronology and prognostic value of the genetic events in MM in order to improve the risk stratification of the patients and hence the choice of treatment. Using cytogenetics (interphase FISH) and molecular biological analyses (SNP, GEP, miRNA) the investigators will study the changes in the myeloma cells. The investigators will search for genetic and clinical differences between patients within the same cytogenetic group and between patients at diagnosis and at relapse. The study population will consist of 100 newly diagnosed patients and 100 relapse patients included prospectively over a 2-year period in a cooperation between the four departments of hematology in Zealand, Denmark.

Hypotheses:

• Early relapse depends on a) molecular defects in the myeloma cells detectable with FISH, GEP, SNP and/or miRNA analyses, and b) the acquisition of new mutations resulting in chemotherapy resistance and increased prolific capacity.
• The progressive reduction of event free survival seen with every relapse until the disease turns refractory can be explained by selection of critical mutations.
• The cytogenetic changes associated with poor prognosis represent a heterogenous group of patients in whom the responsible genetic events remain unknown.

Inclusion criteria

• patients newly diagnosed with multiple myeloma and at the same time eligible for high dose chemotherapy and autologous stem cell transplantation
• patients with multiple myeloma experiencing relapse after high dose chemotherapy and autologous stem cell transplantation

Exclusion criteria

• for newly diagnosed patients: age or comorbidity preventing high dose chemotherapy and autologous stem cell transplantation,
• for all patients: age below 18, physical or psychological incapability to give an informed consent.