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such transcripts (82% vs. 30%; hazard ratio [HR] = 4.80;
95% CI 2.95-7.80; p<0.001). Persistent NPM1-mutated
transcripts were also associated with a lower rate of
overall survival at three years (24% vs. 75%; HR=4.38;
95% CI 2.57-7.47; p<0.001).
In multivariate analysis, which included results of
the targeted sequencing analyses, MRD was the only
independent prognostic factor for mortality (HR=4.84;
95% CI 2.57-9.15; p<0.001) and relapse (HR=5.09; 95%
CI 2.84-9.13; p<0.001).
“Compared with crude genetic information [gathered
via targeted sequencing at baseline], testing whether a patient has a response via MRD is so much more powerful,”
Prof. Grimwade said.
In addition, though mutations associated with preleukemic clones continued to be detectable following
chemotherapy, even when patients were in remission,
detection of NPM1 mutations were more associated
with frank relapse, and were found in 69 of 70 patients
at the time of relapse. Assessing the leukemia-specific
NPM1 mutation in AML patients can be used for
sequential monitoring of MRD to identify impending relapse and to help guide treatment decisions, the
authors added. “The message is not that profiling should
not be performed – because it could identify particular
mutations that could be useful for targeted therapies –
but that we cannot put all our eggs in that basket,” Prof.
Grimwade told ASH Clinical News. “These data have
shown that MRD testing provides independent prognostic information and needs to be on the agenda.”
T:7”
Table 6: Grade 3/4 Adverse Reactions Reported in ≥2% Patients
and With a ≥1% Difference in Proportion of Patients Between the
REVLIMID/dexamethasone and Placebo/dexamethasone groups
System Organ Class/ Preferred Term REVLIMID/Dex# Placebo/Dex#
(N=353)
(N=350)
n (%)
n (%)
Eye Disorders
Cataract
6 (1.7)
1 (0.3)
Cataract Unilateral
5 (1.4)
0 (0.0)
Psychiatric Disorder
Depression
10 (2.8)
6 (1.7)
Venous and Arterial Thromboembolism [see Boxed Warning, Warnings
and Precautions (5.4)]
Deep vein thrombosis (DVT) was reported as a serious (7.4%) or severe
(8.2%) adverse drug reaction at a higher rate in the REVLIMID/dexamethasone
group compared to 3.1 % and 3.4% in the placebo/dexamethasone group,
respectively in the 2 studies in patients with at least 1 prior therapy with
discontinuations due to DVT adverse reactions reported at comparable rates
between groups. In the NDMM study, DVT was reported as an adverse
reaction (all grades: 10.3%, 7.2%, 4.1%), as a serious adverse reaction
(3.6%, 2.0%, 1.7%), and as a Grade 3/4 adverse reaction (5.6%, 3.7%,
2.8%) in the Rd Continuous, Rd18, and MPT Arms, respectively.
Discontinuations and dose reductions due to DVT adverse reactions were
reported at comparable rates between t