Co-Existent Hyperdiploidy Does Not Abrogate The Poor Prognosis Associated With Adverse Cytogenetics In Myeloma

• Published in: Blood 2013-11, Vol.122 (21), p.529-529
• Main Authors: Pawlyn, Charlotte, Melchor, Lorenzo, Boyle, Eileen M, Brioli, Annamaria, Kaiser, Martin F, Gregory, Walter, Drayson, Mark T, Jackson, Graham, Ross, Fiona M, Child, J. Anthony, Morgan, Gareth J, Davies, Faith E
• Format: Article
• Language: English
• ISSN: 0006-4971; 1528-0020
• DOI: 10.1182/blood.V122.21.529.529

The development of the cytogenetic abnormalities hyperdiploidy or a translocation involving the immunoglobulin heavy chain are initiating events in the pathogenesis of myeloma. Previous studies have shown that hyperdiploidy is associated with a more favorable outcome whilst the presence of specific translocations (4;14), (14;16) and (14;20) are associated with poor clinical outcomes especially when they occur in association with other high risk features such as del17p and 1q+. While it has been generally accepted that these events are mutually exclusive, review of a number of clinical datasets shows that they occur together in a significant proportion of cases. This raises the mechanistic issue of which cytogenetic abnormality occurs first as well as the more practical issue of what it means for prognosis. In order to address these important questions we have investigated these cases with interphase FISH (iFISH) as well as determining their outcome in the Myeloma IX study. Myeloma IX is a large study (1960 newly diagnosed myeloma patients) that has been extensively described. iFISH results with a complete data set for hyperdiploidy, adverse IgH translocations, 1q+ and del17p were available for 847 patients with a median follow up of 5.9 years. 58% of patients (499/847) had hyperdiploidy and had a significantly improved survival compared with non-hyperdiploid patients (Median OS 49.7 vs 42.8 months, p=0.016 and PFS 18.8 vs 16.3 months, p=0.028). Hyperdiploid patients were divided into those who had one or more of the adverse lesions t(4;14), t(14;16), t(14;20), del17p and 1q+ (61%, 304/499) and their outcome was compared to those with none (39%, 195/499). The overall and progression free survival was significantly worse for those with hyperdiploidy plus an adverse lesion compared to those with hyperdiploidy alone (Median OS 60.9 vs 35.7 months, p1 lesion groups and a trend towards worse survival for those with an adverse translocation (numbers too small to prove significance) when compared to those with hyperdiploidy and no adverse lesion. (table 1) Table 1HD = HyperdiploidyNo. of patientsPFS (months)OS (months)HD, no