For:
Newly Diagnosed FLT3+ Acute Myeloid Leukemia (AML)
Important Safety Information:

CONTRAINDICATIONS
Do not use in patients with hypersensitivity to midostaurin or its excipients. Hypersensitivity reactions have included anaphylactic shock, dyspnea, flushing, chest pain, and angioed…

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Indication: RYDAPT is indicated, in combination with standard cytarabine and daunorubicin induction and cytarabine consolidation chemotherapy, for the treatment of adult patients with newly diagnosed acute myeloid leukemia (AML) who are FLT3 mutation–positive, as detected by an FDA-approved test.

Limitations of Use
RYDAPT is not indicated as a single-agent induction therapy for the treatment of patients with AML.

Patient Case Studies

Is RYDAPT® (midostaurin) CAPSULES RIGHT for these patients?

 
The following are hypothetical patients.

Steve

Age: 59
ECOG Status: 1
Profession: Painter
Steve
Hypothetical patient.

Patient's clinical presentation

  • Symptoms
    • Fatigue
    • Shortness of breath
    • Night sweats
  • Physical examination
    • Holosystolic murmur
    • Ecchymosis
    • Pallor
  • Laboratory results
    • Bone marrow biopsy = 67% blast cells
    • White blood cells = 39 x 109/L
    • Hemoglobin/hematocrit counts = 9/29
    • Platelets = 113 x 109/L
  • Other investigations
    • 2D echocardiogram = within normal limits and no evidence of cardiac dysfunction
    • Chest X-ray = grade 1 without evidence of pulmonary infiltrates
  • Molecular genetic testing*
    • Comprehensive screening for FLT3 ITD and TKD mutations = FLT3 ITD+

Recommended treatment plan?
RYDAPT in combination with standard cytarabine and daunorubicin induction and high-dose cytarabine consolidation chemotherapy


 

Emily

Age: 67
ECOG Status: 1
Profession: Retired chemical plant worker
Emily
Hypothetical patient.

Patient's clinical presentation

  • Symptoms
    • Fever (101.6°F)
    • Anemia
    • Upper respiratory infection
    • Intermittent fever and chills for past month
    • Bleeding gums with associated gingival hypertrophy
  • Physical examination
    • Right lower lung field crackles on auscultation
    • Abdominal pain and tenderness associated with hepatosplenomegaly
    • No active hepatitis
    • Petechiae on bilateral lower extremities
  • Laboratory results
    • Bone marrow biopsy = 79% blast cells
    • White blood cells = 66 x 109/L
    • Hemoglobin/hematocrit counts = 8/27
    • Platelets = 75 x 109/L
    • ALT/AST = 40/24 U/L
  • Other investigations
    • 2D echocardiogram = within normal limits and no evidence of cardiac dysfunction
    • Chest X-ray = grade 2 with right lower lobe pulmonary infiltrates
  • Molecular genetic testing*
    • Comprehensive screening for FLT3 ITD and TKD mutations = FLT3 TKD+

Recommended treatment plan?
RYDAPT in combination with standard cytarabine and daunorubicin induction and high-dose cytarabine consolidation chemotherapy


 

Philip

Age: 47
ECOG Status: 0
Profession: Petroleum engineer
Philip
Hypothetical patient.

Patient's clinical presentation

  • Symptoms
    • Nausea
    • High cholesterol
    • Bleeding gums with associated gingival hypertrophy
    • Fever (102.1°F)
    • Family history of myelodysplastic syndrome and identical twin brother
  • Physical examination
    • Pallor
    • Dyspnea
    • Purpura on torso
    • Sternal and lower back pain and tenderness
  • Laboratory results
    • Bone marrow biopsy = >90% blast cells
    • White blood cells = 46 x 109/L
    • Hemoglobin/hematocrit counts = 7/25
    • Platelets = 47 x 109/L
  • Other investigations
    • 2D echocardiogram = no wall motion abnormalities or ventricular hypertrophy + HLA identical sibling donor match
    • Chest X-ray = no evidence of pulmonary infiltrates
  • Molecular genetic testing*
    • Comprehensive screening for FLT3 ITD and TKD mutations = FLT3 ITD+

Recommended treatment plan?
RYDAPT in combination with standard cytarabine and daunorubicin induction to achieve complete remission, followed by allogenic stem cell transplant using an identical sibling donor match

*FLT3 mutation testing is performed by The Laboratory for Personalized Molecular Medicine, a subsidiary of Invivoscribe Technologies, Inc., which has gained FDA approval for its FLT3 test as a companion diagnostic for RYDAPT in newly diagnosed FLT3+ AML. Laboratory for Personalized Molecular Medicine® is a registered trademark of Invivoscribe Technologies, Inc.

ALT, alanine aminotransferase; AST, aspartate aminotransferase; ECOG, Eastern Cooperative Oncology Group; FLT3, FMS-like tyrosine kinase 3; HLA, human leukocyte antigen; ITD, internal tandem duplication; TKD, tyrosine kinase domain.

INDICATION for RYDAPT® (midostaurin) capsules

Acute Myeloid Leukemia
RYDAPT is indicated, in combination with standard cytarabine and daunorubicin induction and cytarabine consolidation chemotherapy, for the treatment of adult patients with newly diagnosed acute myeloid leukemia (AML) who are FLT3 mutation–positive, as detected by an FDA-approved test.

Limitations of Use
RYDAPT is not indicated as a single-agent induction therapy for the treatment of patients with AML.

IMPORTANT SAFETY INFORMATION for RYDAPT® (midostaurin) capsules

CONTRAINDICATIONS
  • Do not use in patients with hypersensitivity to midostaurin or its excipients. Hypersensitivity reactions have included anaphylactic shock, dyspnea, flushing, chest pain, and angioedema
WARNINGS AND PRECAUTIONS
Embryofetal Toxicity
  • Do not use during pregnancy. Midostaurin caused severe embryofetal abnormalities and death in animal studies
  • Verify pregnancy status of females of reproductive potential within 7 days prior to initiating RYDAPT
  • Advise females of reproductive potential to use effective contraception during treatment and for at least 4 months after the last dose
  • Males taking RYDAPT should use effective contraception with females of reproductive potential and pregnant women and for at least 4 months after the last dose
  • Pregnancy exposure registry to monitor pregnancy outcomes: Females who may have been exposed to RYDAPT during pregnancy, directly or through a male partner receiving RYDAPT, should contact Novartis Pharmaceuticals Corporation at 1-888-669-6682 and/or at https://psi.novartis.com
Pulmonary Toxicity
  • Cases of interstitial lung disease and pneumonitis, some fatal, have occurred in patients treated with RYDAPT as monotherapy or with chemotherapy
  • Monitor patients for pulmonary symptoms. Discontinue RYDAPT in patients who experience signs or symptoms of interstitial lung disease or pneumonitis without an infectious etiology
ADDITIONAL CONSIDERATIONS
Lactation
  • Because of the potential for serious adverse reactions in breastfed infants from RYDAPT, advise women not to breastfeed during treatment with RYDAPT and for at least 4 months after the last dose
Infertility
  • Based on findings in animals, RYDAPT may impair fertility in females and males of reproductive potential. It is unknown whether these effects on fertility are reversible
Drug Interactions
  • Strong CYP3A4 Inducers: Avoid concomitant use as strong CYP3A4 inducers decrease exposure to midostaurin and may reduce efficacy
  • Strong CYP3A4 Inhibitors: Coadministration with strong CYP3A4 inhibitors may increase midostaurin concentrations and may increase the risk of toxicity. Monitor patients for increased risk of adverse reactions, especially during the first week of RYDAPT use in each chemotherapy cycle and the first week of consecutive RYDAPT administration. Consider alternative therapies that do not strongly inhibit CYP3A4 activity
ADVERSE REACTIONS
Acute Myeloid Leukemia
  • Most common adverse reactions (≥20%) were febrile neutropenia (83%), nausea (83%), mucositis (66%), vomiting (61%), headache (46%), petechiae (36%), musculoskeletal pain (33%), epistaxis (28%), device-related infection (24%), hyperglycemia (20%), and upper respiratory tract infection (20%)
  • Most frequent grade 3/4 adverse reactions (≥10%) were febrile neutropenia (84%), device-related infection (16%), and mucositis (11%)
  • Most common (≥10%) lab abnormalities were alanine aminotransferase increase (71%), hypernatremia (21%), and hypocalcemia (74%)

Please see full Prescribing Information for RYDAPT® (midostaurin) capsules.