P-243: Cytogenetics abnormalities in patients with newly diagnosed multiple myeloma analyzed by fluorescent in situ hybridization in Chilean patients.

Introduction: One of the most relevant points at diagnosis of multiple myeloma (MM) is the identification of adverse prognostic characteristics of the disease, such as clinical features, patient fitness, tumor burden and high risk cytogenetic abnormalities. The use of fluorescence in situ hybridization (FISH) for the genetic classification of newly diagnosed MM (NDMM) has become an essential tool.

There are multiple definitions, but currently patients are considered to have high-risk disease if FISH studies demonstrate one of the following abnormalities: t(4;14), t(14;16), del17p, t(14;20) and gain/amplification of 1q. The occurrence of any two high risk factors is considered double-hit myeloma and three or more high risk factors as triple-hit myeloma.

We aimed to determine the frequency of high risk cytogenetic abnormalities in patients with NDMM in a large cohort of Chilean patients.

Methods: Observational, retrospective, descriptive study based on data recovered from the

Cytogenetics Laboratory of at a National Reference Center for FISH testing from January

2018 to December 2023. FISH is made by immune- magnetic cell sorting. Descriptive statistics were used.

Results: Bone marrow samples from 462 patients were referred for study; 55.4% (n=256) were male, and the mean age of presentation was 63.1 years. Only 51.7% (n=239) were processed.

The most frequent alterations were those involving the immunoglobulin heavy chain (IGH) locus at the chromosome 14q32 region with 39.7% (n= 91/229), including t(11;14) with 15,8% (n=6/38), t(4;14) with 15.6% (n= 30/206) and t(14;16) with 1.5% (n=3/205). The deletion of 17p was observed in 19.8% of the patients (n= 47/237). Gain or amplification of 1q21 occurred in 63% (n=23/36) of the samples tested, 47% (n=11/23) of them being amp(1q), one with seven extra copies. Deletion of the short arm of chromosome 1, 1p32, was observed in 11% (n=4/35).

The proportion of patients labeled as high risk disease were 31% (n=74/239), double-hit myeloma 7,5% (n=18/239) and triple-hit myeloma 0.8% (n=2/239).

Conclusions: This is the most extensive report of cytogenetics alterations in NDMM in the Chilean population so far. Most of our results are similar to those reported in the literature. Until the end of this study, there were no cases of t(14;20) in our patients. We found a high frequency of chromosome 1 abnormalities. This probe has recently been added to our myeloma panel, and few tests were performed during the studied period, which may explain the high rate of positivity.

The most striking finding is that almost half of the samples could not be tested, whether for technical reasons or due to an imposed age limit at the public health system. It is critical that all patients with NDMM be properly stratified.
In conclusion the results are similar to that previously described, except for a higher incidence of gain/amp 1q. We have to optimize the technique and expand the indications for FISH testing.