How to interpret a multiple myeloma Fluorescence In Situ Hybridization (FISH) report?

From the Guidelines

To interpret a myeloma FISH report, focus on identifying high-risk cytogenetic markers including t(4;14), t(14;16), t(14;20), del(17p), and gain(1q), which are associated with poorer outcomes and may warrant more aggressive treatment approaches, as recommended by the NCCN guidelines 1. When reviewing the report, it is essential to consider the following key points:

• High-risk cytogenetic markers, such as t(4;14), t(14;16), t(14;20), del(17p), and gain(1q), are associated with poorer outcomes and may require more aggressive treatment approaches 1.
• Standard-risk findings, including t(11;14), trisomies, and hyperdiploidy, generally indicate better prognosis 1.
• The percentage of plasma cells showing each abnormality is crucial, with higher percentages typically indicating greater disease burden 1.
• Multiple abnormalities may be present simultaneously, with the highest-risk abnormality generally determining the overall risk classification 1. These cytogenetic findings should be integrated with other clinical parameters like stage, renal function, and patient age to guide treatment selection. For high-risk cytogenetics, proteasome inhibitor-based regimens (bortezomib, carfilzomib) are often preferred, while immunomodulatory drugs may be particularly effective for certain abnormalities like t(11;14) 1. Regular reassessment with FISH testing may be necessary during disease progression as the cytogenetic profile can evolve over time 1. It is also important to note that the NCCN guidelines recommend examining for del 13, del 17p13, t(4;14), t(11;14), t(14;16), t(14:20), 1q21 gain/amplification, and 1p deletion in the FISH panel for prognostic estimation of plasma cells 1.

From the Research

Interpreting Myeloma FISH Report

To interpret a myeloma FISH report, it's essential to understand the different cytogenetic abnormalities and their implications on prognosis and treatment.

• Cytogenetic abnormalities such as t(4;14), t(14;16), or del(17p) are associated with poor prognosis in multiple myeloma 2.
• The presence of these abnormalities can be detected using FISH analysis, which can identify clonal heterogeneity and adverse cytogenetic profiles 3.
• A combination of FISH probes, including del(17p13), t(4;14), 1q21 gain, and del(1p32), can enhance the detection of adverse cytogenetic profiles and identify patients with high-risk disease 3.

Prognostic Implications

The prognostic implications of these cytogenetic abnormalities are significant, with patients having adverse abnormalities showing shorter progression-free survival and overall survival 2, 4.

• The accumulation of adverse FISH lesions is associated with a progressive impairment of survival, and patients with multiple adverse lesions have a poorer prognosis 4.
• The International Staging System (ISS) can be integrated with genetic grouping to identify an ultra-high-risk group with a median overall survival of 19.4 months 4.

Treatment Implications

The treatment implications of these cytogenetic abnormalities are also important, with some studies suggesting that bortezomib can improve the prognosis of patients with t(4;14) but not those with del(17p) 5.

• The use of novel agents such as bortezomib and lenalidomide can partially mitigate the poor prognosis associated with t(4;14), but an unmet medical need remains for patients with this aberration 6.
• Preclinical studies of inhibitors of FGFR3 have shown promise in t(4;14) MM, and clinical trials are ongoing to determine the clinical utility of these inhibitors 6.