CLINICAL NEWS
Using Molecular Mutations in Myelodysplastic Syndromes
to Guide Treatment
Two studies presented at the 2015 ASH Annual
Meeting highlighted efforts by researchers to
move beyond current risk stratification models
for patients with myelodysplastic syndromes
(MDS), toward revised models that include
somatic mutations.
Incorporating mutations creates risk
models that more closely reflect real-world
patients with MDS than do currently available
models. Existing prognostic models, such as
the Revised International Prognostic Scoring
System (IPSS-R), were created using treatmentnaïve patients with primary disease who do not
receive therapy subsequently and, therefore, do
not reflect typical MDS patients.
Mutations Predict Overall Survival
Independent of IPSS-R
In the first study, Rafael Bejar, MD, PhD, and
colleagues from the Moores Cancer Center
at the University of California, San Diego,
identified mutations in MDS-associated genes
and clinical outcomes to create a prognostic
model that could provide a deeper level of risk
stratification, regardless of MDS subtype or
prior therapies.
While some mutations have been recognized as important for predicting survival,
they have not been widely accepted among the
medical community, the authors noted. “There
still isn’t consensus on how best to use this
information, or even how best to test for it,” Dr.
Bejar told ASH Clinical News. “Our group is
trying to amass data from around the globe to
see if we can identify a best understanding of
how these mutations affect prognosis and how
we might come to a consensus on how to use
them in the future.”
Dr. Bejar and colleagues pooled data from
3,392 patients with MDS across multiple
centers to determine the relationship between
mutations in MDS-associated genes and clinical measures, such as overall survival (OS).
“We have been able to identify many genes
that have independent significance of the IPPSR and to estimate what that independent risk
is,” said Dr. Bejar.
With a median follow-up of 3.7 years,
median survival among the patient cohort was
2.88 years. Mutations in 12 different genes were
associated with reduced OS, including: ASXL1,
CBL, EZH2, IDH2, NF1, NRAS, PTPN11,
RUNX1, SRSF2, STAG2, TP53, and U2AF1.
Mutations in one gene, SF3B1, were found to
prolong s W'f