ASH Clinical News Focus on Myeloid Malignancies | Page 33

MEETING NEWS
Continued from page 23
Dr. Montalban-Bravo and researchers included 180 previously
untreated patients (median age at diagnosis = 67 years; range = 20-88
years) with MDS (n=143; 79%) or chronic myelomonocytic leukemia
(CMML; n=37; 21%) who were treated at the University of Texas MD
Anderson Cancer Center. Using next-generation sequencing, the
authors analyzed a panel of 28 genes (including ABL1, ASXL1, BRAF,
DNMT3A, EGFR, EZH2, FLT3, GATA1, GATA2, HRAS, IDH1, IDH2,
IKZF2, JAK2, KIT, KRAS, MDM2, MLL, MPL, MYD88, NOTCH1,
NPM1, NRAS, PTPN11, RUNX1, TET2, TP53, and WT1) in patients’
samples collected prior to receiving HMA treatment.
Most patients (60%; n=108) had lower-risk MDS (based on the
International Prognostic Scoring System [IPSS] low- and interme-
diate-1-risk criteria), while 40 percent (n=72) had higher-risk MDS
(based on IPSS intermediate-2- and high-risk criteria). A majority of
patients (n=87; 49%) had normal karyotype, while 20 percent (n=36)
had complex karyotype.
Patients received the following HMAs: azacitidine monotherapy
(n=60; 33%), decitabine monotherapy (n=55; 31%), or guadecitabine
(SGI-110) or combination therapy (n=65; 36%).
The overall response rate (ORR) was 58 percent (n=105), includ-
ing 37 percent (n=66) who achieved complete response (CR).
Sixty-eight percent of patients (n=123) had at least one detectable
mutation, and the median number of mutations was one (range =
0-5 mutations). The most commonly detected mutations were TET2
(23%), TP53 (16%), and RUNX1 (12%).
Contradicting previous research, the presence of TET2 muta-
tion was not significantly associated with an increased likelihood of
response in this series (odds ratio [OR] = 1.32; 95% CI 0.64-2.70;
p=0.453) or CR (OR=1.30; 95% CI 0.64-2.65; p=0.469). However, as
has been reported by other investigators, the ASXL1 mutation was
associated with a decreased chance of achieving CR (OR=0.30; 95%
CI 0.10-0.93; p=0.037).
No differences in ORR were observed based on the presence of
any mutation, but the number of mutations did significantly affect
ORR and CR. Patients who had ≥3 detectable mutations had lower
ORR (OR=0.29; 95% CI 0.10-0.88; p=0.028) and a decreased chance
of achieving CR (OR=0.22; 95% CI 0.05-1.01; p=0.052).
Notably, TET2 mutations did not predict ORR (OR=1.83; 95% CI
0.78-4.25; p=0.163) or CR (OR=1.75; 95% CI 0.80-3.81; p=0.159) in
patients with <3 mutations.
Over a median follow-up of 14.5 months (range = 2.4-101.3
months), patients who did not respond to HMA treatment had
significantly shorter overall survival (OS; not reached [NR] for
responders vs. 21.3 months for non-responders; hazard ratio [HR] =
1.68; 95% CI 1.03-2.73; p=0.037). Leukemia-free survival (LFS) was
also decreased in those who did not achieve a response (NR vs. 34.3
months; HR=2.13; 95% CI 1.00-4.50; p=0.049).
CR was predictive of improved OS in patients with higher-risk
MDS (median OS = NR vs. 14.6 months; p=0.046), but not for
lower-risk patients (median OS = NR vs. 27.3 months; p=0.239). No
significant differences in LFS were observed based on achievement of
CR in both higher- (p=0.238) and lower-risk patients (p=0.453).
“The number of driver mutations may be a new biomarker to
predict response to therapy with hypomethylating agents in patients
with MDS and CMML,” the authors concluded. “Incorporating se-
quencing data at diagnosis may help predict response to therapy and
patient outcomes.” However, because this was a single-center study,
the results may not be generalizable and will need to be confirmed in
larger studies.
Reference
Montalban-Bravo G, Pierola AA, Wang F, et al. Increased number of driver
mutations is a predictor of response to hypomethylating agents in patients with
myelodysplastic syndromes. Abstract #51. Presented at the 2016 ASH Annual
Meeting, December 3, 2016; San Diego, California.
IN THE LITERATURE
AML and Other Myeloid Neoplasms According to WHO
A Look at the Revised Classification
In June 2016 the World Health Organization (WHO) updated
its 2008 classification of tumors of the hematopoietic and
lymphoid tissues. The revised myeloid disorders classification
was published in Blood. 1
“This 2016 classification is not a major overhaul of the disease
categories. Rather, it is intended to incorporate new knowledge
of these disorders obtained since the 2008 publication and is a re-
vision of that classification,” the authors, led by Daniel A. Arber,
MD, from Stanford University in California, explained.
The inclusion of many novel molecular findings with
diagnostic and/or prognostic importance “represents the efforts
of pathologists working closely with clinicians and geneticists,”
Mario Cazzola, MD, a co-author and associate editor of Blood,
wrote in an editorial accompanying the updated classification. 2
“In the next few years, we should continue this collaboration to
further improve the integration of clinical features, morphology,
and genetics.”
Dr. Arber and co-authors explained that several advances neces-
sitated a revised classification, including “discoveries in diagnostic
and prognostic markers; improved characterization and standard-
ization of morphologic features; and the clinical-pathologic studies
May 2017
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