Gene mutation information may improve prognostic models for myelodysplastic syndrome
Including genetic mutations in the current revised International Prognostic Scoring System (IPSS-R) can improve the risk stratification of patients with myelodysplastic syndrome (MDS) and help in identification of patients requiring more aggressive treatment, a recent study has shown.
Multivariate Cox proportional hazards regression analysis showed that aside from older age (relative risk [RR], 1.024; 95 percent CI, 1.014–1.034; p<0.001), mutations in the CBL (RR, 2.292; 1.164–4.513; p=0.016), IDH2 (RR, 1.957; 1.045–3.665; p=0.036), DNMT3A (RR, 1.571; 1.028–2.401; p=0.037), ASXL1 (RR, 1.557; 1.040–2.329; p=0.031) and TP53 (RR, 9.524; 6.067–14.950; p<0.001) genes were independent and significant predictors of poor overall survival (OS; WHO-based Prognostic Scoring System). [Blood Cancer J 2018;8:39]
In contrast, lower IPSS-R scores independently predicted a good OS prognosis (RR, 0.306; 0.208–0.450; p<0.001). The median OS for the cohort was 30.9 months over a median follow-up period of 43.2 months.
Compared to those without, participants with at least one poor-risk mutation (41.8 percent) had a significantly higher risk of leukaemia transformation (5-year rate: 61.7±7.1 percent vs 22.1±4.1 percent; p<0.001) and shorter median OS (15 vs 69.9 months; p<0.001).
Notably, in each IPSS-R risk subgroup, patients with these poor-risk mutations had poorer survival than other members in the same subgroup who did not have the mutations. For instance, molecular information reclassified 22.9 percent of those in the very low/low-risk to the intermediate-risk subgroup.
This upwards reclassification was further observed in 31.5 percent of the intermediate-risk subgroup and 53.8 percent of the high-risk group, who were deemed to be of high-risk and very high-risk, respectively, after taking genetic mutation information into consideration.
Researchers observed a similar trend of worse OS outcomes in those with vs without a poor-risk mutation within the same 2016 (WPSS) subgroup.
“Patients with these poor-risk mutations had an OS worse than others in the same IPSS-R or 2016 WHO subgroup, but similar to those in the next higher risk subgroup. These findings explain the clinical heterogeneity in the same IPSS-R risk groups,” said researchers.
“The incorporation of the status of these poor-risk mutations into the survival analysis would be especially helpful to identify patients with poorer prognosis for more aggressive treatment in the rather heterogeneous group of patients with lower risk MDS defined by conventional scoring systems,” they added.
For the present study, bone marrow cells were collected from 426 adult patients with primary MDS (median age at diagnosis 67 years). Only those with complete clinical, mutational and cytogenetic information were eligible. Following DNA extraction, mutational analysis of 25 relevant genes was performed.
The WPSS and IPSS-R are international prognostic models designed to facilitate the classification of MDS patients according to risk, and to aid in making clinical decisions. However, recent discoveries pertaining to genetic alterations that may also affect patient survival have yet to be included in these prognostic systems, noted researchers. [J Clin Oncol 2007;25:3503-3510; Blood 1997;89:2079-2088; Blood 2013;122:3616-3627]
“Because the median survival and risk of leukaemia transformation vary widely in the MDS patients, even in the same IPSS or IPSS-R group, it is prudent to identify novel prognostic markers to make the prediction more accurate,” they added.