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 R/R AML WITH AN IDH2 MUTATION
START WITH IDHIFA® AND STAY WITH IDHIFA®*
TARGETED THERAPY DELIVERED IN AN ORAL TABLET
*Evaluated in an open-label, single-arm, multicenter, clinical trial of patients who had R/R AML with 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. Efficacy was established in 199 patients based on the rate of complete response (CR) and CR with partial hematologic recovery (CRh) (23%; 95% CI, 18%-30%), median duration of CR/CRh (8.2 months; 95% CI, 4.3-19.4), and rate of conversion from transfusion dependence to independence (34%).
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QUICK TRIVIA!
Which of the following is the NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines®) recommendation for IDH2 testing?1
Select one below, then hit submit to see the correct answer or continue scrolling.
QUICK TRIVIA!
Which of the following is the NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines®) recommendation for IDH2 testing?1
The correct answer is...
Keep scrolling to see how IDHIFA® may help your patients who have R/R AML with an IDH2 mutation
Did you know?
NCCN Guidelines® recommend enasidenib (IDHIFA®) for R/R AML with an IDH2 mutation1
—
IDHIFA® is the only targeted inhibitor of mutant IDH2
See how IDHIFA® targets mutant IDH2 to
release the block on myeloid differentiation
Explore the pivotal data below
Response Rates
FDA approval of IDHIFA® was based on results from
THE FIRST PIVOTAL TRIAL EXCLUSIVELY IN R/R AML WITH AN IDH2 MUTATION
IDHIFA® was studied in an open-label, single-arm, multicenter, clinical trial of patients who had R/R AML with an IDH2 mutation
199 patients
Efficacy Analysis
214 patients
Safety Analysis
- Starting dose of 100 mg daily by mouth until disease progression or unacceptable toxicity
- Dose reductions were allowed to manage adverse events
- IDH2 mutations were either prospectively identified or retrospectively confirmed by the Abbott RealTime™ IDH2 assay
- Patients were a median age 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 response‡, 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 CR requirement for blast count, no evidence of disease, but only partial recovery of peripheral blood counts (platelets >50,000/µL and ANC >500/µL).
‡Duration of response was defined as time since first response of CR or CRh to relapse or death, whichever is earlier.
§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.
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Efficacy results are just a scroll away
SELECTED BASELINE CHARACTERISTICS
| Demographic and disease characteristics | R/R AML, N=199 (%) 100-mg daily dose |
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| Median age in years | 68 (range, 19-100)
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| Median time from initial AML diagnosis in months (172 patients) | 11.3 (range, 1.2-129.1) | ||||||||||
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| Prior stem cell transplantation for AML | 25 (13) | ||||||||||
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| Transfusion dependent at baselinec | 157 (79) | ||||||||||
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aOne patient had missing baseline ECOG PS.
bFor 3 patients with different mutations detected in bone marrow compared to blood, the result of blood is reported.
cPatients were defined as transfusion dependent at baseline if they received any RBC or platelet transfusions within the 8-week baseline period.
dIncludes intensive and/or nonintensive therapies.
ECOG PS, Eastern Cooperative Oncology Group performance status.
In this challenging clinical setting,
IDHIFA® ACHIEVED DURABLE AND CLINICALLY MEANINGFUL RESPONSES
RATE OF CR/CRh
n=46/199
(95% CI, 18%-30%)
(95% CI, 13%-25%)
n=9/199
(95% CI, 2%-8%)
MEDIAN DURATION CR/CRh
achieving CR/CRh
achieving CR
achieving CRh
NA, not available.
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ADDITIONAL OUTCOMES: BEST OBJECTIVE RESPONSE2
Figure depicts the FDA-adjudicated CR/CRh rates and other parameters retrospectively determined by the sponsor using the pivotal data set (N=199).
n=65/199
(95% CI, 26%-40%)
(95% CI, 13%-25%)
(95% CI, 2%-8%)
n=4/199
(n=94/199)
STABLE DISEASE
(n=23/199)
PROGRESSIVE DISEASE
(n=1/199)
NOT EVALUABLE
Overall response rate (ORR) is defined as CR + CRh + PR + MLFS.
aPercentages are based on the number of subjects in each group.
MLFS, morphologic leukemia-free state for subjects with AML; PR, partial response.
LIVE POLL!
When do you expect to see a potential CR or CRh after starting a patient on IDHIFA®?
Select one below, then hit submit to see how others responded or continue scrolling.
LIVE POLL!
Your response has been recorded. See below for how others responded.
When do you expect to see a potential CR or CRh after starting a patient on IDHIFA®?
Poll Results
More data below
Did you know?
WITH IDHIFA®, RESPONSES DEEPENED OVER TIME FOR SOME PATIENTS ACHIEVING CR/CRh
MEDIAN TIME TO FIRST AND BEST RESPONSE
To allow time for clinical response, continue patients on IDHIFA® for at least 6 months or until disease progression or unacceptable toxicity
Expert Views
EXPERT VIEWPOINT: WATCH A theoretical PATIENT CASE DISCUSSION
Dr Hetty Carraway and Dr Daniel A Pollyea discuss a theoretical patient with R/R AML who relapsed after intensive induction therapy, the decision to start IDHIFA®, and outcomes from the pivotal trial
I educate patients regarding what to expect…both patients and practitioners should recognize that responses to IDHIFA® may not be immediate, and that responses could deepen over time.
– Dr Daniel A Pollyea, MD, MS
Dr Hetty Carraway is an Associate Professor of Medicine at the Cleveland Clinic.
Dr Daniel A Pollyea is an Associate Professor of Medicine and Clinical Director of Leukemia Services, Division of Hematology at the University of Colorado School of Medicine.
Resource Corner
Support for when you're talking to appropriate patients about IDHIFA®
Download the “Starting Treatment”
guide for patients
See transfusion data and safety below
Transfusion Independence
ACHIEVING TRANSFUSION INDEPENDENCE IS CLINICALLY MEANINGFUL
(n=53/157)
34% of patients who were RBC and/or platelet transfusion dependent at baseline achieved transfusion independence during any 56-day post-baseline period*
- Of these 53 patients, 27 had not achieved a CR/CRh at the time of follow-up2
(n=32/42)
76% of patients who were independent of both RBC and platelet transfusions at baseline remained transfusion independent during any 56-day post-baseline period
43% of patients (85/199) on IDHIFA® became or remained transfusion independent during any 56-day post-baseline period
*Patients were defined as transfusion independent if they received no RBC or platelet transfusions within any 56-day post-baseline period.
SEE MORE DATA
For transfusion status by patient response
ADDITIONAL DATA FOR TRANSFUSION STATUS IN PATIENTS WHO HAD R/R AML WITH AN IDH2 MUTATION2
TRANSFUSION STATUS BY RESPONSE TYPE (N=199)
| Post-baseline TI | Post-baseline TD | |
| CR/CRh (n=46) | ||
| RBC or platelet TD at baseline | 26 | 3 |
| RBC or platelet TI at baseline | 16 | 1 |
| Total | 42 | 4 |
| NON-CR/CRh (n=153) | ||
| RBC or platelet TD at baseline | 27 | 101 |
| RBC or platelet TI at baseline | 16 | 9 |
| Total | 43 | 110 |
| All (N=199) | ||
| RBC or platelet TD at baseline | 53 | 104 |
| RBC or platelet TI at baseline | 32 | 10 |
| Total | 85 | 114 |
TD, transfusion dependent;
TI, transfusion independent.
Safety
IDHIFA® OFFERS A DIFFERENT SAFETY PROFILE IN R/R AML
Adverse Reactions (ARs) reported in ≥10% (any grade) or ≥3% (grades 3-5) of patients with R/R AML
| Body system AR | All grades N=214 (%) | ≥Grade 3 N=214 (%) |
|---|---|---|
| Gastrointestinal disordersa | ||
| Nausea | 107 (50) | 11 (5) |
| Diarrhea | 91 (43) | 17 (8) |
| Vomiting | 73 (34) | 4 (2) |
| Metabolism and nutrition disorders | ||
| Decreased appetite | 73 (34) | 9 (4) |
| Tumor lysis syndrome (TLS)b | 13 (6) | 12 (6) |
| Blood and lymphatic system disorders | ||
| Differentiation syndromec | 29 (14) | 15 (7) |
| Noninfectious leukocytosis | 26 (12) | 12 (6) |
| Nervous system disorders | ||
| Dysgeusia | 25 (12) | 0 (0) |
aGastrointestinal disorders observed with IDHIFA® treatment can be associated with other commonly reported events, such as abdominal pain and weight decrease.
bTLS observed with IDHIFA® treatment can be associated with commonly reported uric acid increase.
cDifferentiation syndrome can be associated with other commonly reported events such as respiratory failure, dyspnea, hypoxia, pyrexia, peripheral edema, rash, or renal insufficiency.
- Other clinically significant ARs occurring in ≤10% of patients included:
- Respiratory, thoracic, and mediastinal disorders (pulmonary edema, acute respiratory distress syndrome)
- The median duration of exposure to IDHIFA® was 4.3 months (range, 0.3 to 23.6)
SEE MORE
For laboratory abnormalities
Keep scrolling to see the frequency of ARs over time
Most common (≥20%) new or worsening laboratory abnormalities reported in patients with R/R AML
| Parametera | All grades (%) | ≥Grade 3 (%) |
|---|---|---|
| Total bilirubin increased | 81 | 15 |
| Calcium decreased | 74 | 8 |
| Potassium decreased | 41 | 15 |
| Phosphorus decreased | 27 | 8 |
aIncludes abnormalities occurring up to 28 days after last IDHIFA® dose, if new or worsened by at least 1 grade from baseline, or if baseline was unknown. The denominator varies based on data collected for each parameter (N=213, except phosphorus [N=209]).
ADDITIONAL ANALYSIS: THE FREQUENCY OF ARs OVER TIME2
ARs reported in ≥10% (any grade) or ≥3% (grades 3-5) of patients with R/R AML
PLACEHOLDER CONTENT
DIFFERENTIATION SYNDROME MAY OCCUR WITH IDHIFA®
It may be life-threatening or fatal if not treated
Differentiation syndrome is associated with rapid proliferation and differentiation of myeloid cells.
(n=15/214)
Differentiation syndrome has been observed with and without concomitant hyperleukocytosis, as early as 1 day and up to 5 months after IDHIFA® initiation
Resource Corner
Wallet cards for your patients taking IDHIFA® and their caregivers
These wallet cards are an easy method for alerting medical personnel outside their regular healthcare team about IDHIFA® treatment and differentiation syndrome
Keep scrolling to see a discussion on patient management, as well as dose modifications from the trial
EXPERT VIEWPOINT: WATCH NOW
Dr Harry Erba and Marilyn Pritchard, RN discuss managing patients receiving IDHIFA®, including diagnosing and treating differentiation syndrome and other adverse events
Distinguishing differentiation syndrome from progressive disease can be difficult. That’s because the symptoms of differentiation syndrome are nonspecific and can resemble progressing AML.
– Dr Harry Erba, MD, PhD
DOSE MODIFICATIONS IN THE CLINICAL TRIAL
DOSE INTERRUPTION
(n=92/214)
43% of patients experienced an AR leading to dose interruption
- The most common ARs leading to interruption were differentiation syndrome (4%) and leukocytosis (3%)
DOSE REDUCTION
(n=10/214)
5% of patients had a dose reduction due to an AR
- No AR required dose reduction in more than 2 patients
THERAPY DISCONTINUATION
(n=36/214)
17% of patients permanently discontinued therapy due to an AR
- The most common reason for discontinuation was leukocytosis (1%)
SEE RECOMMENDATIONS
Dose modifications for ARs
Next up, dosing
Dose modifications for IDHIFA®-related toxicities
| Adverse reaction | Recommended action |
|---|---|
| Differentiation syndrome |
|
| Noninfectious leukocytosis (WBC count greater than 30x109/L) |
|
| Elevation of bilirubin greater than 3x the ULN sustained for ≥2 weeks without elevated transaminases or other hepatic disorders |
|
| Other Grade 3a or higher toxicity considered related to treatment, including TLS |
|
aGrade 1 is mild, Grade 2 is moderate, Grade 3 is serious, Grade 4 is life-threatening.
ULN, upper limit of normal.
Dosing
IDHIFA® OFFERS CONVENIENT, DAILY ORAL THERAPY THAT PATIENTS CAN TAKE AT HOME
Starting dose: one 100-mg IDHIFA® tablet, once daily.
Also available in 50-mg tablets
Swallow whole with water. Do not split or crush the tablets.
Take IDHIFA® tablets orally about the same time each day with or without food.
- IDHIFA® should be taken until disease progression or unacceptable toxicity
- If dose is vomited, missed, or not taken at the usual time, administer the dose as soon as possible on the same day and return to the normal schedule the following day
- Assess blood counts and blood chemistries for leukocytosis and TLS prior to the initiation of IDHIFA® and monitor at a minimum of every 2 weeks for at least the first 3 months during treatment. Manage any abnormalities promptly
There are no contraindications to IDHIFA®.
Scroll down to see available resources
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FOR PATIENTS WHO HAVE R/R AML WITH AN IDH2 MUTATION
START WITH IDHIFA® AND STAY WITH IDHIFA®*
TARGETED THERAPY DELIVERED IN AN ORAL TABLET
*Evaluated in an open-label, single-arm, multicenter, clinical trial of patients who had R/R AML with 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. Efficacy was established in 199 patients based on the rate of complete response (CR) and CR with partial hematologic recovery (CRh) (23%; 95% CI, 18%-30%), median duration of CR/CRh (8.2 months; 95% CI, 4.3-19.4), and rate of conversion from transfusion dependence to independence (34%).
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