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Testing for FLT3 early at AML diagnosis can help with clinical outcomes.
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| Prompt, comprehensive testing for FLT3 in adults with newly diagnosed AML is critical* |
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| Identifying patients who are FLT3 mutation-positive (FLT3+) can help make a difference.1 |
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WHY
FLT3 is a selective marker
Only patients newly diagnosed as FLT3+ with ITD or TKD mutations may be eligible to receive RYDAPT® (midostaurin) capsules. FLT3+ status is a prerequisite.2
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WHO
Every patient with newly diagnosed AML
Approximately 30% of all patients with AML are FLT3+.1
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WHEN
At diagnosis
In parallel with cytogenetics.3 Results are needed by Day 8 after start of induction chemotherapy.2
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HOW
Use the FDA-approved LeukoStrat® CDx FLT3 Mutation Assay
This assay is used as an aid in the selection of patients with AML for RYDAPT treatment.2 Send out samples early to ensure fast and complete test results.†
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Clinical recommendations for AML testing from the College of American Pathologists-American Society of Hematology (CAP-ASH) guidelines and the National Comprehensive Cancer Network® (NCCN®)3,4
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CAP-ASH |
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NCCN |
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Molecular genetic
testing at diagnosis |
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Screening for specific genetic mutations in all patients with newly diagnosed AML |
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Ensure testing for FLT3-ITD
Consider IDH1, IDH2, TET2, WT1, DNMT3A, TP53, KIT, NPM1, CEBPA, and/or
RUNX1‡
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KIT, FLT3-ITD,
FLT3-TKD, IDH1, IDH2, TP53, NPM1, CEBPA, and other mutations
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INDICATION
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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.
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LIMITATIONS OF USE
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RYDAPT is not indicated as a single-agent induction therapy for the treatment of patients with AML.
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IMPORTANT SAFETY INFORMATION for RYDAPT® (midostaurin) capsules
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CONTRAINDICATIONS
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Do not use in patients with hypersensitivity to midostaurin or its excipients. Hypersensitivity reactions have included anaphylactic shock, dyspnea, flushing, chest pain, and angioedema
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WARNINGS AND PRECAUTIONS
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Embryofetal Toxicity
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Do not use during pregnancy. Midostaurin caused severe embryofetal abnormalities and death in animal studies |
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Verify pregnancy status of females of reproductive potential within 7 days prior to initiating RYDAPT |
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Advise females of reproductive potential to use effective contraception during treatment and for at least 4 months after the last dose |
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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 |
Pulmonary Toxicity
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Cases of interstitial lung disease and pneumonitis, some fatal, have occurred in patients treated with RYDAPT as monotherapy or with chemotherapy |
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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
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Lactation
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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
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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
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Strong CYP3A4 Inducers: Avoid concomitant use as strong CYP3A4 inducers decrease exposure to midostaurin and may reduce efficacy |
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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
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Acute Myeloid Leukemia
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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%)
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Most frequent grade 3/4 adverse reactions (≥10%) were febrile neutropenia (84%), device-related infection (16%), and mucositis (11%) |
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Most common (≥10%) lab abnormalities were alanine aminotransferase increase (71%), hypernatremia (21%), and hypocalcemia (74%) |
Please see full Prescribing Information for RYDAPT® (midostaurin) capsules.
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FLT3 mutation testing is performed by the Laboratory for Personalized Molecular Medicine® (LabPMM)®, 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.
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Samples must be received by LabPMM within a maximum of 5 days after collection.
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For adult patients with confirmed core binding factor (CBF) AML (AML with t(8;21)(q22;q22.1); RUNX1-RUNX1T1 or inv(16)(p13.1q22) /t(16;16)(p13.1;q22); CBFB-MYH11), the pathologist or treating clinician should ensure that appropriate mutational analysis for KIT is performed. For patients other than those with confirmed CBF-AML, acute promyelocytic leukemia, or AML with myelodysplasia-related cytogenetic abnormalities, the pathologist or treating clinician should also ensure that mutational analysis for NPM1, CEBPA, and RUNX1 is also performed.
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FLT3, FMS-like tyrosine kinase 3; ITD, internal tandem duplication; TKD, tyrosine kinase domain.
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References:
1. Levis M. FLT3 mutations in acute myeloid leukemia: what is the best approach in 2013? Hematology Am Soc Hematol Educ Program. 2013;2013:220-226.
2. Rydapt [prescribing information]. East Hanover, NJ: Novartis Pharmaceuticals Corp; 2017.
3. Arber DA, Borowitz MJ, Cessna M, et al. Initial diagnostic workup of acute leukemia: guideline from the College of American Pathologists and the American Society of Hematology. Arch Pathol Lab Med. 2017;141(10):1342-1393.
4. Referenced with permission from the NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines®) for Acute Myeloid Leukemia V.1.2018. © National Comprehensive Cancer Network, Inc. 2018. All rights reserved. Accessed February 14, 2018. To view the most recent and complete version of the guideline, go online to NCCN.org.
The National Comprehensive Cancer Network makes no warranties of any kind whatsoever regarding their content, use or application and disclaims any responsibility for their application or use in any way.
Laboratory for Personalized Molecular Medicine is a registered trademark of Invivoscribe Technologies, Inc.
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