On Location
Conference Coverage
ADVANCES IN CANCER RESEARCH
he American Association for
Cancer Research’s 2019 Annual
Meeting, held March 29 to April 3
in Atlanta, brought together more
than 21,000 researchers, clinicians,
and members of the international cancer
community to discuss cutting-edge basic,
translational, and clinical research updates in
oncology.
Outgoing AACR President Elizabeth Jaffee, MD, at the 2019 AACR Annual Meeting’s closing ceremony.
Here, we present highlights from the hema-
tologic research presented at the meeting,
including gilteritinib for relapsed/refractory
acute myeloid leukemia, new markers of
response in patients treated with chimeric
antigen receptor T-cell therapy, and more.
Gilteritinib Superior to Standard Chemotherapy in Relapsed/Refractory
FLT3-Mutated Acute Myeloid Leukemia
Treatment with the oral FLT3/AXL
inhibitor gilteritinib led to longer overall
survival (OS) in patients with relapsed/
refractory FLT3-mutated acute myeloid
leukemia (AML), compared with standard
chemotherapy, according to results from
the phase III ADMIRAL trial presented at
the 2019 American Association for Cancer
Research Annual Meeting. Lead author
Alexander Perl, MD, from Perelman
School of Medicine at the University of
Pennsylvania, presented the findings.
However, while gilteritinib was associ-
ated with high response and survival, most
participants were not considered cured
and long-term survival was poor in both
arms, Dr. Perl told ASH Clinical News.
The U.S. Food and Drug Administration
(FDA) approved gilteritinib in November
2018 based on interim safety and efficacy data
from the ADMIRAL trial. In this analysis, Dr.
Perl shared results from the final analysis of
ADMIRAL, which enrolled individuals with
clinically confirmed FLT3-mutated AML
who had an untreated first relapse or whose
disease was refractory to induction chemo-
therapy. Patients who had previously taken
FLT3 inhibitors other than midostaurin or
sorafenib were excluded from the analysis.
A total of 371 patients (median age = 62
years; range = 19-85 years) were randomized
38
ASH Clinical News
2:1 to receive either:
• gilteritinib administered in continuous
28-day cycles of 120 mg/day (n=247)
• standard salvage chemotherapy
(low-dose cytarabine, azacitidine,
mitoxantrone/etoposide/cytarabine,
or fludarabine/cytarabine/granulocyte
colony-stimulating factor/idarubicin)
(n=124)
Most patients (60.6%) had relapsed AML
and 39.4% had refractory AML. Baseline
FLT3 mutations included:
• FLT3-ITD (88.4%)
• FLT3-TKD (8.4%)
• both FLT3-ITD and FLT3-TKD
(1.9%)
• unconfirmed (1.3%)
In the gilteritinib-treated group, patients
had significantly longer OS compared with
the standard treatment group: 9.3 months
versus 5.6 months (hazard ratio [HR]
= 0.637; p=0.0007). One-year survival
rates for gilteritinib and chemotherapy
groups were 37.1% and 16.7% respectively,
although p values for the comparison were
not reported. Median event-free survival
had a trend toward improvement with
gilteritinib: 2.8 months versus 0.7 months
(HR=0.793; p=0.083).
More patients in the gilteritinib group
achieved a complete remission/complete
remission with partial hematologic re-
covery (CR/CRh): 34.0% vs. 15.3% in the
chemotherapy group (p=0.0001).
The most frequently reported adverse
events (AEs) across both treatment groups
included:
• febrile neutropenia (43.7%)
• anemia (43.4%)
• pyrexia (38.6%)
Grade ≥3 AEs associated with gilteritinib
included anemia (19.5%), febrile neutro-
penia (15.4%), and thrombocytopenia
(12.2%). The rate of serious treatment-
emergent AEs per patient-year appeared
lower with gilteritinib than chemotherapy
(7.1% vs. 9.2%; p value not reported).
When asked about the study’s limitations,
Dr. Perl noted that “we enrolled relatively
few patients with FLT3-TKD mutations,
which limited our ability to compare its ef-
ficacy in this subgroup with chemotherapy.
Although gilteritinib had comparable remis-
sion rates and OS in FLT3-ITD and FLT3-
TKD groups, the small sample size limited
us from robustly demonstrating survival
benefits for the FLT3-TKD subgroup.”
The standard frontline treatment for
FLT3-mutated AML also shifted during
enrollment for ADMIRAL, with the FDA
approval of the FLT3 inhibitor midostaurin
in April 2017. Some patients may have re-
ceived prior FLT3-targeting therapy, which
could potentially confound the results.
“Our biggest priority in the field is to
optimize frontline therapy to prevent,
rather than treat, relapsed/refractory
AML,” Dr. Perl concluded. “To this end,
trials of gilteritinib as part of induction,
consolidation, and maintenance therapy
for AML have been initiated. We hope
that this will change the natural history
of the disease and improve cure rate.”
The authors report relationships with
Astellas, which sponsored the trial.
REFERENCE
Perl AE, Martinelli G, Cortes JE, et al. Gilteritinib significantly prolongs
overall survival in patients with FLT3-mutated (FLT3 mut+ ) relapsed/
refractory (R/R) acute myeloid leukemia (AML): Results from the phase
III ADMIRAL trial. Abstract #CT184. Presented at the American Association
for Cancer Research Annual Meeting, April 2, 2019; Atlanta, GA.
June 2019