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Full Prescribing Information  |  Med Guide/IFU

Full Prescribing Information

Med Guide/IFU

Important Safety Information

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Revuforj® (revumenib) Logo

Revuforj is a menin inhibitor indicated for the treatment of relapsed or refractory acute leukemia with a
lysine methyltransferase 2A gene (KMT2A) translocation in adult and pediatric patients 1 year and older.

Safety

Safety and tolerability of a targeted therapy

The safety of Revuforj reflects exposure in 135 patients (104 adult and 31 pediatric) with relapsed or refractory acute leukemia with a KMT2A translocation

  • Patients received a dose approximately equivalent to 160 mg in adults orally twice daily with a strong CYP3A4 inhibitor

  • Median duration of exposure to Revuforj was 2.3 months (range: <1–23 months)

  • 3% of patients were exposed for more than 6 months

Adverse reactions reported in ≥20% (any Grade) or ≥5% (Grade 3 or 4) in patients with R/R acute leukemia with a KMT2A translocation (N=135)

Adverse
Reaction

All Grades
(%)

Grade
3 or 4
(%)

Vascular disorders

Hemorrhagea*

53

9

Thrombosisb

10

3

Gastrointestinal disorders

Nauseac

51

4

Diarrhead

30

4

Constipation

23

1

Musculoskeletal and connective tissue disorders

Musculoskeletal paine

42

6

Infections and infestations

Infectionf

41

29

Bacterial infectiong

31

20

Viral infectionh

23

4

Adverse
Reaction

All Grades
(%)

Grade
3 or 4
(%)

Blood and lymphatic system disorders

Febrile neutropenia

35

33

Leukocytosis

8

5

Neoplasms benign, malignant, and unspecified (including cysts and polyps)

Differentiation syndrome*

29

13

Investigations

Electrocardiogram
QT prolonged

29

12

Metabolism and nutrition disorders

Decreased appetite

24

8

General disorders and administration site conditions

Edemai

23

1

Fatiguej

22

5

  • Includes the following fatal adverse reactions: differentiation syndrome (n=2); hemorrhage (n=1).

See complete definitions of grouped terms.

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Low discontinuation rate due to adverse reactions

Select the + below to see the adverse reactions leading to dose modifications

12

%

permanent
discontinuation

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42

%

dose
interruptions

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10

%

dose
reductions

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Selected new or worsening laboratory abnormalities in patients with R/R acute leukemia with a KMT2A translocation

Laboratory
Abnormality

Grades
1-4*
(%)

Grades
3-4
(%)

Phosphate increased

50

–

Aspartate aminotransferase increased

37

1

Alanine aminotransferase increased

33

3

Parathyroid hormone, intact increased

33

–

Phosphate decreased

25

–

Triglycerides increased

25

3

Potassium decreased

24

5

Alkaline phosphatase increased

21

0

Cholesterol increased

19

0

Creatinine
increased

19

0

Calcium
corrected
increased

15

0

The denominator used to calculate the rate varied from 73 to 135 based on the number of patients with a baseline value and at least 1 post-baseline value.

CYP3A4=cytochrome P450 3A4; KMT2A=lysine methyltransferase 2A; R/R=relapsed/refractory.

Differentiation syndrome, which can be fatal, has occurred with Revuforj

In clinical trials, differentiation syndrome occurred in 29% of patients (39/135), including:

  • 32% of patients with AML

  • 25% of patients with MPAL

  • 14% of patients with ALL

The median time to onset was 10 days (range 3-41
days)

  • Differentiation syndrome was Grade 3 or 4 in 13% of patients and fatal in one

  • Some patients experienced more than 1 event of differentiation syndrome

  • Treatment interruption was required for 7% of patients, and treatment was withdrawn for 1%

Symptoms of differentiation syndrome, including those seen in patients treated with Revuforj, include:

  • Fever

  • Dyspnea

  • Hypoxia

  • Peripheral edema

  • Pleuropericardial effusion

  • Acute renal failure

  • Hypotension

Advise patients and their caregivers to contact their healthcare team or go to the nearest hospital emergency room immediately if the patient develops any of these symptoms while taking Revuforj

Encourage your patients to download the Differentiation Syndrome Wallet Card

WALLET CARD

Reduce the white blood cell count to less than 25 Gi/L prior to starting Revuforj
 If differentiation syndrome is suspected, immediately initiate treatment with systemic corticosteroids for a minimum of 3 days and until resolution of signs and symptoms.

Treatment example:

Icon of an adult

Patients ≥40 kg:

dexamethasone 10-mg IV

every 12 hours

Icon of a child

Patients <40 kg:

dexamethasone 0.25-mg/kg/dose
IV every 12 hours

Institute supportive measures and hemodynamic monitoring until improvement
 Interrupt Revuforj if severe signs and/or symptoms persist for more than 48 hours after initiation of systemic corticosteroids, or earlier if life-threatening symptoms occur such as pulmonary symptoms requiring ventilator support. Restart steroids promptly if differentiation syndrome recurs after tapering corticosteroids.

Review Dose Modifications for how to manage differentiation syndrome and other adverse reactions.

ALL=acute lymphoblastic leukemia;
AML=acute myeloid leukemia;
MPAL=mixed-phenotype acute leukemia.

Additional Warnings & Precautions

Icon of QTc interval

QTc interval prolongation

In the clinical trials, QTc interval prolongation was reported as an adverse reaction in 29% of patients (39/135), including:

  • 16% of the 31 patients less than 17 years old

  • 33% of the 88 patients 17 years to less than
    65 years old

  • 50% of the 16 patients 65 years or older

The heart-rate corrected QT interval (using Fridericia’s method) (QTcF) was greater than 500 msec in 8%,
and the increase from baseline QTcF was greater than 60 msec in 18%.

  • QTc interval prolongation was Grade 3 in 12%

    of patients

  • Revuforj dose reduction was required for 5% due to QTc interval prolongation

Review the Monitoring Guidance for QTc prolongation.

Icon of QTc interval

Embryo-fetal toxicity

Revuforj can cause fetal harm when administered to a pregnant woman. Advise pregnant women of the potential risk to a fetus.

Advise females of reproductive potential and males with female partners of reproductive potential to use effective contraception during treatment with Revuforj and for 4 months after the last dose of Revuforj.

Verify pregnancy status in females of reproductive potential within 7 days prior to initiating Revuforj.

NEXT: DOSING & MANAGEMENT

Reference: Revuforj® [Prescribing Information]. Waltham, MA: Syndax Pharmaceuticals Inc.; November 2024.

IMPORTANT SAFETY
INFORMATION AND INDICATION

WARNING: DIFFERENTIATION SYNDROME

Differentiation syndrome, which can be fatal, has occurred with Revuforj. Signs and symptoms may include fever, dyspnea, hypoxia, pulmonary infiltrates, pleural or pericardial effusions, rapid weight gain or peripheral edema, hypotension, and renal dysfunction. If differentiation syndrome is suspected, immediately initiate corticosteroid therapy and hemodynamic monitoring until symptom resolution.

WARNINGS AND PRECAUTIONS

Differentiation syndrome: Revuforj can cause fatal or life-threatening differentiation syndrome (DS). Symptoms of DS, including those seen in patients treated with Revuforj, include fever, dyspnea, hypoxia, peripheral edema, pleuropericardial effusion, acute renal failure, and/or hypotension. In clinical trials, DS occurred in 39 (29%) of 135 patients treated with Revuforj. DS was Grade 3 or 4 in 13% of patients and fatal in one. The median time to onset was 10 days (range 3-41 days). Some patients experienced more than 1 DS event. Treatment interruption was required for 7% of patients, and treatment was withdrawn for 1%.


Reduce the white blood cell count to less than 25 Gi/L prior to starting Revuforj. If DS is suspected, immediately initiate treatment with systemic corticosteroids (e.g., dexamethasone 10-mg IV every 12 hours in adults or dexamethasone 0.25-mg/kg/dose IV every 12 hours in pediatric patients weighing less than 40 kg) for a minimum of 3 days and until resolution of signs and symptoms. Institute supportive measures and hemodynamic monitoring until improvement. Interrupt Revuforj if severe signs and/or symptoms persist for more than 48 hours after initiation of systemic corticosteroids, or earlier if life-threatening symptoms occur such as pulmonary symptoms requiring ventilator support. Restart steroids promptly if DS recurs after tapering corticosteroids.


QTc interval prolongation: In the clinical trials, QTc interval prolongation was reported as an adverse reaction in 39 (29%) of 135 patients treated with Revuforj. QTc interval prolongation was Grade 3 in 12% of patients. The heart-rate corrected QT interval (using Fridericia’s method) (QTcF) was greater than 500 msec in 8%, and the increase from baseline QTcF was greater than 60 msec in 18%. Revuforj dose reduction was required for 5% of patients due to QTc interval prolongation. QTc prolongation occurred in 16% of the 31 patients less than 17 years old, 33% of the 88 patients 17 years to less than 65 years old, and in 50% of the 16 patients 65 years or older.


Correct electrolyte abnormalities, including hypokalemia and hypomagnesemia, prior to treatment with Revuforj. Perform an electrocardiogram (ECG) prior to initiation of Revuforj, and do not initiate Revuforj in patients with QTcF >450 msec. Perform an ECG at least once weekly for the first 4 weeks and at least monthly thereafter. In patients with congenital long QTc syndrome, congestive heart failure, electrolyte abnormalities, or those who are taking medications known to prolong the QTc interval, more frequent ECG monitoring may be necessary. Concomitant use with drugs known to prolong the QTc interval may increase the risk of QTc interval prolongation.

  • Interrupt Revuforj if QTcF increases >480 msec and <500 msec, and restart Revuforj at the same dose twice daily after the QTcF interval returns to ≤480 msec
  • Interrupt Revuforj if QTcF increases >500 msec or by >60 msec from baseline, and restart Revuforj twice daily at the lower-dose level after the QTcF interval returns to ≤480 msec
  • Permanently discontinue Revuforj in patients with ventricular arrhythmias and in those who develop QTc interval prolongation with signs or symptoms of life-threatening arrhythmia

Embryo-fetal toxicity: Revuforj can cause fetal harm when administered to a pregnant woman. Advise pregnant women of the potential risk to a fetus. Advise females of reproductive potential and males with female partners of reproductive potential to use effective contraception during treatment with Revuforj and for 4 months after the last dose of Revuforj.


ADVERSE REACTIONS

Fatal adverse reactions occurred in 4 (3%) patients who received Revuforj, including 2 with differentiation syndrome, 1 with hemorrhage, and 1 with sudden death.


Serious adverse reactions were reported in 99 (73%) patients. The most frequent serious adverse reactions (≥5%) were infection (24%), febrile neutropenia (19%), bacterial infection (17%), differentiation syndrome (12%), hemorrhage (9%), and thrombosis (5%).


The most common adverse reactions (≥20%) including laboratory abnormalities, were hemorrhage (53%), nausea (51%), phosphate increased (50%), musculoskeletal pain (42%), infection (41%), aspartate aminotransferase increased (37%), febrile neutropenia (35%), alanine aminotransferase increased (33%), parathyroid hormone intact increased (33%), bacterial infection (31%), diarrhea (30%), differentiation syndrome (29%), electrocardiogram QT prolonged (29%), phosphate decreased (25%), triglycerides increased (25%), potassium decreased (24%), decreased appetite (24%), constipation (23%), edema (23%), viral infection (23%), fatigue (22%), and alkaline phosphatase increased (21%).


DRUG INTERACTIONS

Drug interactions can occur when Revuforj is concomitantly used with:

  • Strong CYP3A4 inhibitors: reduce Revuforj dose

  • Strong or moderate CYP3A4 inducers: avoid concomitant use with Revuforj

  • QTc-prolonging drugs: avoid concomitant use with Revuforj. If concomitant use is unavoidable, obtain ECGs when initiating, during concomitant use, and as clinically indicated. Withhold Revuforj if the QTc interval is >480 msec.
    Restart Revuforj after the QTc interval returns to ≤480 msec


SPECIAL POPULATIONS

Lactation: advise lactating women not to breastfeed during treatment with Revuforj and for 1 week after the last dose.


Pregnancy and testing: Revuforj can cause fetal harm when administered to a pregnant woman. Verify pregnancy status in females of reproductive potential within 7 days prior to initiating Revuforj.


Pediatric: monitor bone growth and development in pediatric patients.


Geriatric: compared to younger patients, the incidences of QTc prolongation and edema were higher in patients 65 years and older.


Infertility: based on findings in animals, Revuforj may impair fertility. The effects on fertility were reversible.


To report SUSPECTED ADVERSE REACTIONS, contact Syndax Pharmaceuticals at 1-888-539-3REV or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.


INDICATION

Revuforj® (revumenib) is a menin inhibitor indicated for the treatment of relapsed or refractory acute leukemia with a lysine methyltransferase 2A gene (KMT2A) translocation in adult and pediatric patients 1 year and older.


Please see Full Prescribing Information, including BOXED WARNING.

IMPORTANT SAFETY
INFORMATION AND INDICATION

IMPORTANT SAFETY
INFORMATION AND INDICATION

WARNING: DIFFERENTIATION SYNDROME

Differentiation syndrome, which can be fatal, has occurred with Revuforj. Signs and symptoms may include fever, dyspnea, hypoxia, pulmonary infiltrates, pleural or pericardial effusions, rapid weight gain or peripheral edema, hypotension, and renal dysfunction. If differentiation syndrome is suspected, immediately initiate corticosteroid therapy and hemodynamic monitoring until symptom resolution.