CLINICAL NEWS
TABLE 1.
Response Rates by Study Cohort
N
Composite
Response Rate
(CR+CRi), n (%) Overall
Response Rate
(CR+CRi+PR), n (%) Median duration
of CR+CRi, months
(95% CI) Median OS, months
(95% CI)
All patients 145 [54+43]
97 (67) [54+43+2]
99 (68) 11.3 (8.9-NR) 17.5 (12.3-NR)
Venetoclax 400 mg + HMA 60 44 (73) 44 (73) 12.5 (7.8-NR) NR (11.0-NR)
29 22 (76) 22 (76) NR (5.6-NR) NR (9.0-NR)
Azacitidine
Decitabine
Venetoclax 800 mg + HMA
31 22 (71) 22 (71) 12.5 (5.1-NR) 14.2 (7.7-NR)
74 48 (65) 50 (68) 11.0 (6.5-12.9) 17.5 (10.3-NR)
Azacitidine 37 21 (57) 22 (59) 11.7 (4.6-12.9) 15.2 (9.1-NR)
Decitabine 37 27 (73) 28 (76) 9.2 (5.9-NR) 17.5 (10.3-NR)
Venetoclax 1,200 mg + HMA
11 5 (45) 5 (45) 9.4 (4.1-NR) 11.4 (0.9-NR)
Azacitidine 6 2 (33) 2 (33) 6.7 (4.1-9.4) 8.8 (0.9-NR)
Decitabine 5 3 (60) 3 (60) NR (NR-NR) NR (12.4-NR)
CR = complete response; CRi = CR with incomplete hematologic recovery; PR = partial response; NR = not reached; HMA = hypomethylating agent; OS = overall survival
hematologic disease [rather
than venetoclax treatment],” the
researchers wrote.
They also observed a trend
toward higher rates of hemato-
logic and gastrointestinal AEs
in the 1,200-mg versus 400- and
800-mg groups (p>0.05), result-
ing in dose reduction to 800 mg
in five patients. A total of 101 pa-
tients discontinued the study, the
majority of whom experienced
progressive disease.
Approximately 3 percent of
the cohort died within 30 days
following the first drug dose.
In the entire intent-to-treat
population, the overall response
rate (ORR) – which included
complete response (CR), CR with
incomplete hematologic recovery
(CRi), and partial response – was
68 percent. Specifically, the rates
of CR and CRi were 37 percent
and 30 percent, respectively.
Details about other secondary
efficacy endpoints are presented
in TABLE 1 .
In the dose-expansion cohort,
the authors did not observe
differences in ORR or CR/CRi
rates between the two venetoclax
doses:
• ORR: 73% in the 400 mg
group vs. 68% in the 800 mg
group (p=0.57)
• CR/CRi: 73% vs. 65%
(p=0.35)
“Notably, the venetoclax 400 mg/
HMA cohort achieved a CR/CRi
rate of 73 percent, a median dura-
tion of CR/CRi of 12.5 months,
and median overall survival (OS)
not reached,” the authors reported.
A phase III study of venetoclax
400 mg combined with azacitidine
in adults with untreated AML who
are ineligible for induction therapy
is underway.
Bone marrow minimal re-
sidual disease (MRD) evaluations
(assessed via multiparameter flow
cytometry) were available for
83 of the 97 patients (86%) who
achieved a CR/CRi. Of these, 28
patients (29%) had at least one
assessment with an MRD of <10 -3 .
Most of these MRD-responders
were in the lower-dose venetoclax
group: 17 at venetoclax 400 mg,
10 at 800 mg, and one at 1,200
mg. Neither median duration of
response or OS had been reached
at time of last follow-up.
Subgroup analyses also
revealed that venetoclax
combinations were similarly
effective in patients with poor-
and intermediate-risk cytogenetic
profiles (CR/CRi rate = 60% and
74%, respectively), in patients >75
years (CR/CRi rate = 65%), and
in patients with secondary AML
(67%).
Although the researchers
noted that these results compare
favorably with results from trials
of HMA monotherapy, they ac-
knowledged that the findings from
this early-phase trial are limited by
the lack of a comparator arm.
The authors report financial rela-
tionships with AbbVie and Genen-
tech, which supported the trial.
REFERENCE
DiNardo CD, Pratz K, Pullarkat V, et al. Venetoclax
combined with decitabine or azacitidine in treatment-
naive, elderly patients with acute myeloid leukemia. Blood.
2018 October 25. [Epub ahead of print]
No Benefit With Adding Eltrombopag to Azacitidine in Patients
With Higher-Risk MDS
In the phase III SUPPORT trial, re-
searchers tested the hypothesis that
concomitant administration of the
thrombopoietin receptor agonist
eltrombopag could ameliorate the
thrombocytopenic effects of azaciti-
dine, a standard frontline treatment
for patients with intermediate- or
high-risk myelodysplastic syn-
dromes (MDS). While earlier trials
showed “an acceptable safety profile
of eltrombopag in patients with
low-risk and high-risk MDS and
positive outcomes on thrombocy-
topenia,” the authors of an analysis
published in Blood found no benefit
when it was added to azacitidine
treatment.
ASHClinicalNews.org
Michael Dickinson, MD, from
the Peter MacCallum Cancer Cen-
tre and Royal Melbourne Hospital
in Australia, and authors enrolled
adults diagnosed with intermedi-
ate- or high-risk MDS (defined as
Int-1, Int-2, or high risk per the
International Prognostic Scoring
System [IPSS]) between June 2014
and December 2015. Participants
also were required to have platelet
counts <75×10 9 /L within 28 days
before the first dose of azacitidine.
Patients were randomized
based on IPSS risk score, baseline
platelet count, and platelet
transfusion dependence to
receive azacitidine with either
eltrombopag (n=179) or placebo
(n=177). Azacitidine 75 mg/m 2
was administered as a once-daily
subcutaneous injection for a total
of seven days during 28-day cycles.
Continuous doses of eltrombopag
or placebo were administered at
200 to 300 mg/day starting on day
1 of azacitidine therapy.
Mean platelet counts in
patients randomized to eltrom-
bopag increased gradually during
the study and to a greater degree
than observed for those receiving
placebo, though p values for this
comparison were not reported.
Patients received eltrombopag for
a median of 83 days (range = 1-477
Concomitant administration of
eltrombopag did not
improve rates of transfusion
independence.
ASH Clinical News
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