According to results of a study comparing CD38-positive tumor cells ofpatients with newly diagnosed multiple myeloma, a high-risk status determinedby either a validated gene-expression profiling assay or the presence of specificchromosomal abnormalities was independently predictive of poor outcome. Thesefindings were published in Leukemia.1
Because survival rates of patients with newly diagnosed multiplemyeloma can vary widely, it is important to identify those with high-riskdisease characterized by a more aggressive clinical course who may require a newtherapeutic approach.
Chromosomal aberrations known to be associated with more aggressivedisease include translocations t(4;16), t(14;16), and t(14;20), as well as thepresence of 4 or more copies of the 1q chromosome, as well as deletion of bothcopies of chromosome 17p. In particular, previous studies of patients with multiplemyeloma have shown low survival rates in those with disease characterized bythe presence of 2 or more of these genetic features (ie, a double hit). Inaddition, other methods that have been validated for the prediction of outcomein patients with multiple myeloma include gene-expression assays, such as the SKY92MMproflier (SKY92), and the International Staging System(ISS), as well as the combination of these 2 methods.2
In this study, the presence or absence of chromosomal aberrations, aswell as SKY92 expression profiles of 92 genes, were evaluated in CD38-postivetumor cells from a cohort of 329 patients with newly diagnosed multiple myelomareceiving intensive therapy in the NCRI Myeloma XI trial.
A comparison ofthe 81 patients in this cohort with disease characterized by a high-riskgene-expression profile showed median overall survival (OS) was significantlyshorter (36.7 months) compared with the subgroup with disease that lacked this gene-expressionsignature (median OS not reached; hazard ratio HR, 3.9; 95% CI, 2.7-5.7; P =2.5 x 10-13).
On multivariable analyses, a high-risk SKY92 profile (HR, 2.7; 95% CI, 1.84.2; P =4.4 106), high-risk chromosomal translocations (HR 1.8; 95% CI, 1.22.9; P =.007), and deletion of the 17p chromosome (HR; 2.5, 95% CI, 1.54.1; P =.0007) were all found to be independently associated with worse OS compared with patients without these markers of high-risk disease.
Furthermore,high-risk SKY92 and double-hit were independently prognostic by multivariableanalysis, with HRs for OS of 2.9 (95% CI, 1.94.2;P=2.6 107)and 2.3
(95%CI, 1.53.6; P=.0002) compared with subgroups withoutthese markers.
Percentagesof the 3 subgroups defined by a high-risk SKY92 profile and/or high-riskchromosomal marker(s), and the hazard ratios for OS for these subgroupscompared with the subgroup without these disease markers, were as follows:
Ofnote, these findings were validated in a separate cohort of 116 patientsenrolled in the transplant arm of MRC Myeloma IX study of newly diagnosed patientswith multiple myeloma.
The study authors stated that these results highlight the molecular diversity of [multiple myeloma] and demonstrate that single time point combined GEP and chromosomal profiling at diagnosis can predict clinical outcome with significant precision
References
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Gene-Expression Profiling Assay Predicts Survival in Newly Diagnosed Multiple Myeloma - Cancer Therapy Advisor
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