Clinicians’ Perspectives and Methodological Application of Fluorescence in situ Hybridization (FISH) to Define Cytogenetic Risk in Multiple Myeloma: An Italian, Real-World, Survey-Based Report From the European Myeloma Network (EMN) Italy

Background: Fluorescence in situ hybridization (FISH) is the standard technique for the prognostic detection of cytogenetic abnormalities (CA) in multiple myeloma (MM). In Italy, the application of practical guidelines for FISH testing in clinical studies and the degree of standardization of laboratory techniques are largely unknown. Methods: We conducted a survey from April to July 2023 among 70 MM-treating centers associated with the European Myeloma Network Italy and geographically well distributed across Italy. We aimed to record laboratory and clinicians’ perspectives about FISH application in Italy, with a focus on 1q alterations. Results: FISH was widely accessible across the country, with 71% of centers performing it locally, while the remaining centers (predominantly those with <30 newly diagnosed MM cases/year) sent samples to external laboratories. Variability in laboratory techniques, such as CD138+ cell purification and CA detection thresholds, was observed among centers. The centers analyzed del(17p) (100%), t(4;14) (100%), t(14;16) (98%), 1q+ (96%, with 70% distinguishing between gain and amplification), t(11;14) (90%), del(1p32) (88%), del(13q) (68%), and hyperdiploidy (52%). FISH emerged as a crucial prognostic technique, since 94% of centers used the Revised International Staging System (R-ISS) at diagnosis, and 69% implemented the recent R2-ISS. Most centers performed FISH at diagnosis in all patients, while others did not routinely perform FISH in some categories of patients (e.g., aged >80 years). At relapse, 53% of centers routinely repeated FISH testing, 9% did not, while others repeated it selectively. Conclusions: This overview of FISH use in Italy provides a basis for future standardization efforts.