Abstract
Cytogenetic evaluation at the time of diagnosis is essential for risk stratification in multiple myeloma, however little is known about the occurrence and prognostic significance of cytogenetic evolution during follow-up. We studied 989 patients with multiple myeloma, including 304 patients with at least two cytogenetic evaluations. Multivariable-adjusted regression models were used to assess the associations between the parameters of interest and cytogenetic evolution as well as overall survival. The prognostic significance of baseline cytogenetic abnormalities was most pronounced at the time of diagnosis and attenuated over time. In the patients with serial cytogenetic evaluations, the presence of t(11;14) at the time of diagnosis was associated with decreased odds of cytogenetic evolution during follow-up (odds ratio (OR)=0.22, 95% confidence interval (CI)=0.09–0.56, P=0.001), while the presence of at least one trisomy or tetrasomy was associated with increased odds (OR=2.96, 95% CI=1.37–6.42, P=0.006). The development of additional abnormalities during the 3 years following diagnosis was associated with increased subsequent mortality (hazard ratio=3.31, 95% CI=1.73–6.30, P<0.001). These findings emphasize the importance of the underlying clonal disease process for risk assessment and suggest that selected patients may benefit from repeated risk stratification.
Highlights
Two distinct oncogenic pathways have been implicated in the molecular pathogenesis of multiple myeloma.1 One pathway is characterized by the occurrence of translocations involving the immunoglobulin heavy chain locus,2 the other one by multiple trisomies of odd-numbered chromosomes.3 The involved pathway and the presence of specific cytogenetic abnormalities at the time of diagnosis have been shown to be of prognostic significance.4–7 The occurrence of cytogenetic abnormalities has been implicated in disease progression8,9 but it is hitherto unknown which factors are determining the subsequent development of cytogenetic abnormalities and whether or not these abnormalities are of prognostic significance later on in the course of disease
Adjusting for the same factors as before, the number of abnormalities at the time of diagnosis was the only characteristic associated with increased odds of loss of abnormalities during the follow-up (OR = 1.49 for each abnormality present at the time of diagnosis, 95% confidence interval (CI) = 1.20–1.85, P o0.001)
The patients who underwent serial cytogenetic evaluations were younger at the time of diagnosis and experienced longer overall survival compared with the patient with a single cytogenetic evaluation, reflecting the fact that these patients had to survive long enough to undergo repeated cytogenetic evaluation
Summary
Two distinct oncogenic pathways have been implicated in the molecular pathogenesis of multiple myeloma.1 One pathway is characterized by the occurrence of translocations involving the immunoglobulin heavy chain locus (non-hyperdiploid pathway),2 the other one by multiple trisomies of odd-numbered chromosomes (hyperdiploid pathway).3 The involved pathway and the presence of specific cytogenetic abnormalities at the time of diagnosis have been shown to be of prognostic significance.4–7 The occurrence of cytogenetic abnormalities has been implicated in disease progression8,9 but it is hitherto unknown which factors are determining the subsequent development of cytogenetic abnormalities and whether or not these abnormalities are of prognostic significance later on in the course of disease. All the models were adjusted for sex, age, the presence of high-risk abnormalities, the number of abnormalities at the time of diagnosis and the time between the first and last cytogenetic evaluation.
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