Role of Conventional Karyotyping in Multiple Myeloma in the Era of Modern Treatment and FISH Analysis.

Background: The Revised International Staging System (R-ISS) has been widely adopted to prognosticate multiple myeloma. As a result, the continued utility of conventional metaphase karyotyping has been called into question.

Patients And Methods: A multi-center study for newly diagnosed patients with multiple myeloma who received novel agent(s) at induction was conducted. Conventional metaphase karyotype information was categorized based on ploidy. We evaluated the impact of ploidy on overall survival (OS) including multivariate analysis, taking into account the R-ISS stages, transplant status, age, and novel agent(s) used at induction. We also evaluated if it is possible to identify high-risk (HR) patients with conventional karyotyping when a fluorescence in situ hybridization analysis is not available. Results were validated in an independent cohort.

Results: There were 308 patients evaluable. Ploidy significantly affected the OS of patients with R-ISS stage II, with non-hyperdiploid patients doing the worst. In the multivariate analysis, ploidy was significantly associated with OS. R-ISS stage II patients with or without non-hyperdiploid karyotype had significantly different survival. We replaced HR fluorescence in situ hybridization abnormalities with HR metaphase karyotypic abnormalities (non-hyperdiploid karyotype). When compared with R-ISS, there was a high level of concordance in HR patients identified using HR karyotypic abnormalities. These results were validated with an independent cohort of 375 patients.

Conclusion: Conventional metaphase karyotyping is an independent prognostic factor even in the setting of R-ISS.