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. 2012 Feb;26(2):349-55.
doi: 10.1038/leu.2011.204. Epub 2011 Aug 12.

A novel prognostic model in myeloma based on co-segregating adverse FISH lesions and the ISS: analysis of patients treated in the MRC Myeloma IX trial

K D Boyd  1 , F M Ross, L Chiecchio, G P Dagrada, Z J Konn, W J Tapper, B A Walker, C P Wardell, W M Gregory, A J Szubert, S E Bell, J A Child, G H Jackson, F E Davies, G J Morgan; NCRI Haematology Oncology Studies Group
Affiliations

A novel prognostic model in myeloma based on co-segregating adverse FISH lesions and the ISS: analysis of patients treated in the MRC Myeloma IX trial

K D Boyd et al. Leukemia. 2012 Feb.

Abstract

The association of genetic lesions detected by fluorescence in situ hybridization (FISH) with survival was analyzed in 1069 patients with newly presenting myeloma treated in the Medical Research Council Myeloma IX trial, with the aim of identifying patients associated with the worst prognosis. A comprehensive FISH panel was performed, and the lesions associated with short progression-free survival and overall survival (OS) in multivariate analysis were +1q21, del(17p13) and an adverse immunoglobulin heavy chain gene (IGH) translocation group incorporating t(4;14), t(14;16) and t(14;20). These lesions frequently co-segregated, and there was an association between the accumulation of these adverse FISH lesions and a progressive impairment of survival. This observation was used to define a series of risk groups based on number of adverse lesions. Taking this approach, we defined a favorable risk group by the absence of adverse genetic lesions, an intermediate group with one adverse lesion and a high-risk group defined by the co-segregation of >1 adverse lesion. This genetic grouping was independent of the International Staging System (ISS) and so was integrated with the ISS to identify an ultra-high-risk group defined by ISS II or III and >1 adverse lesion. This group constituted 13.8% of patients and was associated with a median OS of 19.4 months.

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Figures

Figure 1
Figure 1
Venn diagram of the relationship of each of the adverse FISH groups (adverse IGH translocations, +1q21 and del(17p13)).
Figure 2
Figure 2
OS of each of the adverse FISH lesions when they occur in isolation compared to samples lacking any adverse lesions.
Figure 3
Figure 3
OS graded by number of adverse lesions, showing the progressive impact of accumulation of adverse lesions.
Figure 4
Figure 4
A – PFS of genetic risk groups defined by the presence of 0, 1 and >1 adverse FISH lesions respectively. B – OS of genetic risk groups defined by the presence of 0, 1 and >1 adverse FISH lesions respectively.
Figure 4
Figure 4
A – PFS of genetic risk groups defined by the presence of 0, 1 and >1 adverse FISH lesions respectively. B – OS of genetic risk groups defined by the presence of 0, 1 and >1 adverse FISH lesions respectively.
Figure 5
Figure 5
Integration of the ISS and FISH groups to identify an ultra-high risk group, defined by ISS II or III with >1 adverse lesion.
See this image and copyright information in PMC

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