Proliferation is a central independent prognostic factor and target for personalized and risk-adapted treatment in multiple myeloma

Proliferation is a central independent prognostic factor and target for personalized and risk-adapted treatment in multiple myeloma

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Background Proliferation of malignant plasma cells is a strong adverse prognostic factor in multiple myeloma and simultaneously targetable by available (e.g.tubulin polymerase inhibitors) and upcoming (e.g.

aurora kinase inhibitors) compounds.Design and Methods We assessed proliferation using gene expression-based indices in 757 samples including independent cohorts of 298 and 345 samples of CD138-purified myeloma cells from previously untreated patients undergoing high-dose chemotherapy, together with clinical prognostic factors, chromosomal aberrations, and gene expression-based high-risk scores.Results In the two cohorts, 43.3% and 39.

4% of the myeloma cell samples showed a Hammocks proliferation index above the median plus three standard deviations of normal bone marrow plasma cells.Malignant plasma cells of patients in advanced stages or those harboring disease progression-associated gain of 1q21 or deletion of 13q14.3 showed significantly higher proliferation indices; patients with gain of chromosome 9, 15 or 19 (hyperdiploid samples) had significantly 5 Piece Outdoor Seating Set lower proliferation indices.Proliferation correlated with the presence of chromosomal aberrations in metaphase cytogenetics.

It was significantly predictive for event-free and overall survival in both cohorts, allowed highly predictive risk stratification (e.g.event-free survival 12.7 versus 26.

2 versus 40.6 months, P.