CLINICAL NEWS
Evaluating Midostaurin Plus Intensive Chemotherapy
in Older Patients With AML
Midostaurin plus intensive chemother-
apy, followed by allogeneic hematopoi-
etic cell transplantation (alloHCT) and
single-agent midostaurin maintenance
therapy, was improved survival outcomes
in patients with newly diagnosed, FLT3-
ITD-positive acute myeloid leukemia
(AML), though the authors observed a
high rate of cardiac toxicities in older pa-
tients during treatment. The results of the
phase II study, which were published in
Blood, also suggest that only a small sub-
set of patients could tolerate midostaurin
as maintenance therapy.
“The role of alloHCT in first complete
remission (CR) to overcome the nega-
tive impact of FLT3-ITD … on survival
remains controversial,” wrote Richard
F. Schlenk, MD, from the University
Hospital of Ulm in Germany, and co-
authors. But, according to their findings,
“midostaurin significantly improved
event-free survival [EFS; compared with
historical controls] and alloHCT in first
remission after midostaurin and chemo-
therapy is feasible and highly effective,
irrespective of age.”
This hypothesis-generating trial
enrolled adult patients (age range = 18-70
years) with newly diagnosed FLT3-ITD-
positive AML. A total of 284 patients
(median age = 54.1 years; range = 18-70
years) started induction therapy, which
consisted of one cycle of 7+3 cytarabine and
daunorubicin with twice-daily midostaurin
50 mg starting on day eight until 48 hours
before the start of the next chemotherapy
cycle. Of the total, 279 patients (98%)
received at least one dose of midostaurin.
At the end of induction therapy, the
rate of CR or CR with incomplete hema-
tologic recovery (CRi) was 76.4 percent,
which was similar between younger and
older patients (75.8% for 18-60 years vs.
77.9% for 61-70 years; p=0.76). However,
the mortality rate was higher among
older than younger patients (10.5% vs.
3.5%; p=0.03).
The 247 participants (72.9%) who
achieved a CR/CRi during induction
proceeded to consolidation therapy with
either alloHCT (n=207) or high-dose
cytarabine with midostaurin (n=40).
Maintenance therapy (consisting of
twice-daily midostaurin 50 mg for 365
days) was administered to 97 patients
(34%): 75 of the 134 (56%) who underwent
alloHCT and 22 of 40 (55%) who received
high-dose cytarabine consolidation.
The median time on maintenance ther-
apy after alloHCT and high-dose cytara-
bine was 9 months (range = 1-13) and 10.5
months (range = 1-12), respectively, and
maintenance was terminated early in 44
patients (58.7%) and 16 patients (72.7%).
“Early discontinuation due to
non-relapse causes was common after
ASHClinicalNews.org
alloHCT (86%), whereas relapse and
non-relapse causes were nearly equally
distributed after [high-dose cytarabine],”
the authors reported. “Thus, midostaurin
maintenance therapy added some degree
of toxicity, especially after alloHCT
with anticipated interactions between
midostaurin and immunosuppressants
and anti-infectives.”
“The toxicity rates in our study
were comparable to those observed in
the RATIFY study [which supported
midostaurin’s regulatory approval],” the
authors reported. However, 22 percent
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