IDHIFA® (enasidenib) is indicated for the treatment of adult patients with relapsed or
refractory (R/R) acute myeloid leukemia (AML) with an isocitrate dehydrogenase-2 (IDH2)
mutation as detected by an FDA-approved test.
FOR PATIENTS WITH R/R AML AND AN IDH2 MUTATION
MYELOID DIFFERENTIATION
OPENS UP THE POSSIBILITIES
IDHIFA: The first and only oral, targeted inhibitor of IDH2
23
%
Rate of complete response
(CR)* or CR with partial
hematologic recovery (CRh)†
8.2 mo
Median duration of CR/CRh ‡
n=46/199
(95% CI, 4.3-19.4)
n=46/199
(95% CI, 18%-30%)
34
%
Rate of conversion from
transfusion dependence to
transfusion independence
(RBC and platelet)
n=53/157
IDHIFA was studied in an open-label, single-arm, multicenter, clinical trial of patients with R/R AML and an IDH2 mutation who
were assigned a starting dose of 100 mg daily until disease progression or unacceptable toxicity. Dose reductions were allowed
to manage adverse events. Patients’ IDH2 mutations were either prospectively identified or retrospectively confirmed by the
Abbott RealTime™ IDH2 assay. § Patients were a median of 68 years old and had a median of 2 prior therapies.
Efficacy was established on the basis of the rate of CR/CRh, the duration of CR/CRh, and the rate of conversion from
transfusion dependence to transfusion independence. || The median follow-up was 6.6 months (range, 0.4 to 27.7).
* CR was defined as <5% of blasts in the bone marrow, no evidence of disease, and full recovery of peripheral blood counts (platelets >100,000/μL and ANC >1,000/μL).
CRh was defined as <5% of blasts in the bone marrow, no evidence of disease, and partial recovery of peripheral blood counts (platelets >50,000/μL and ANC >500/μL).
‡
Duration of CR/CRh was defined as time since first response of CR or CRh to relapse or death, whichever is earlier.
§
Abbott RealTime™ IDH2 assay is the FDA-approved test for selection of patients with AML for treatment with IDHIFA.
||
Patients were defined as transfusion independent if they received no RBC or platelet transfusions within any 56-day post-baseline period.
ANC, absolute neutrophil counts; CI, confidence interval; RBC, red blood cell; R/R, relapsed/refractory.
†
IMPORTANT SAFETY INFORMATION
WARNING: DIFFERENTIATION SYNDROME
Patients treated with IDHIFA have experienced
symptoms of differentiation syndrome, which can
be fatal if not treated. Symptoms may include fever,
dyspnea, acute respiratory distress, pulmonary
infiltrates, pleural or pericardial effusions, rapid
weight gain or peripheral edema, lymphadenopathy,
bone pain, and hepatic, renal, or multi-organ
dysfunction. If differentiation syndrome is suspected,
initiate corticosteroid therapy and hemodynamic
monitoring until symptom resolution.
WARNINGS AND PRECAUTIONS
Differentiation Syndrome: See Boxed WARNING.
In the clinical trial, 14% of patients treated with IDHIFA
experienced differentiation syndrome, which may be
life-threatening or fatal if not treated. Differentiation
syndrome has been observed with and without
concomitant hyperleukocytosis, as early as 10 days and
at up to 5 months after IDHIFA initiation. Symptoms in
patients treated with IDHIFA included acute respiratory
distress represented by dyspnea and/or hypoxia and
need for supplemental oxygen; pulmonary infiltrates and
pleural effusion; renal impairment; fever; lymphadenopathy;
bone pain; peripheral edema with rapid weight gain;
and pericardial effusion. Hepatic, renal, and multi-organ
dysfunction have also been observed. If differentiation
syndrome is suspected, initiate systemic corticosteroids
and hemodynamic monitoring until improvement. Taper
corticosteroids only after resolution of symptoms.
Differentiation syndrome symptoms may recur with
premature discontinuation of corticosteroids. If severe
pulmonary symptoms requiring intubation or ventilator
support and/or renal dysfunction persist for more than
48 hours after initiation of corticosteroids, interrupt
IDHIFA until signs and symptoms are no longer severe.
Hospitalization for close observation and monitoring of
patients with pulmonary and/or renal manifestation is
recommended.
Embryo-Fetal Toxicity: Based on animal embryo-fetal
toxicity studies, IDHIFA can cause embryo-fetal harm when
administered to a pregnant woman. Advise females of
reproductive potential and males with female partners of
reproductive potential to use effective contraception during
treatment with IDHIFA and for at least 1 month after the last
dose. Pregnant women, patients becoming pregnant while