Gains on Chromosome Band 9q34 Could Represent a Novel Independent Prognostic Marker in Multiple Myeloma Patients Receiving High-Dose Chemotherapy with Autologous Stem Cell Transplantation.

Introduction: Genomic aberrations represent important prognostic markers in many hematological cancers. In multiple myeloma (MM), chromosome 13q deletion (13q-) has emerged as one of the most important outcome predictors and indicates a dismal prognosis. Other chromosomal abnormalities have been discussed as prognostic markers in this disease but came not out as independent variables when they were tested in a multivariate fashion. However, the complexity of genomic rearrangements and the clinical heterogeneity seen in malignant plasma cell disorders argue against 13q- as the sole genomic change of prognostic relevance.

Material and Methods: In a retrospective analysis, 109 patients (pts.) treated with one or two cycles of high-dose chemotherapy (HD-CTX) followed by autologous stem cell transplantation (ASCT) at a single center were analyzed by tri-color FISH and four DNA probes mapping to chromosome bands 1q21, 9q34, 11q25, and 13q14. The selection of DNA probes based upon previous data from a comprehensive molecular cytogenetic study that revealed a high incidence of chromosomal gains (+) and losses (−) involving these four loci. The Cox proportional hazards regression model was applied to correlate molecular cytogenetic markers with clinical data.

Results: The most frequent chromosomal abnormalities in the present series were +9q (49%), +1q (48%), +11q (47%), and 13q- (42%). The median follow-up time was 30 months (m) and the median event free survival (EFS) and overall survival (OS) time (calculated from first ASCT) of the entire cohort was 30 m and 71 m, respectively. There were 52 events (31 deaths). In a multivariable analysis including the four most frequent chromosomal abnormalities, +9q (hazard ratio 2.49, 95% CI 1.20-5.18; p=.01) and 13q- (2.34, 1.17–4.68; p=.02) were statistically significant risk factors for shorter EFS. The median EFS in pts. lacking both genomic changes was 3.6 years , while it was 2.5 years in pts. with either +9q or 13q- and only 1.5 years in pts. that exhibited both chromosomal abnormalities. Of note, when other potential prognostic factors ß2-microglobulin, albumin, number of chemotherapy cycles prior to first ASCT) were included in the multivariable analysis, +9q and 13q- remained independent risk factors for shorter EFS (p=.008 and p=.03, respectively). Due to the diversity of salvage treatment protocols applied after relapse, OS was not analyzed in this study.

Conclusions: +9q34 could represent a novel independent marker of adverse prognosis in MM pts. receiving HD-CTX with ASCT. The prognostic significance of +9q34 and other molecular cytogenetic aberrations is currently investigated within large multicenter trials on more homogenously treated cohorts of pts.