Midostaurin (Rydapt) Form

Midostaurin (Rydapt®) is a kinase inhibitor. FDA Approved Indication(s) Rydapt is indicated for the treatment of adult patients with: • Newly diagnosed acute myeloid leukemia (AML) that is FLT3 mutation-positive as detected by an FDA-approved test, in combination with standard cytarabine and daunorubicin induction and cytarabine consolidation Limitation(s) of use: Rydapt is not indicated as a single-agent induction therapy for the treatment of patients with AML. • Aggressive systemic mastocytosis (ASM), systemic mastocytosis with associated hematological neoplasm (SM-AHN), or mast cell leukemia (MCL) Policy/Criteria Provider must submit documentation (such as office chart notes, lab results or other clinical information) supporting that member has met all approval criteria.
It is the policy of health plans affiliated with Centene Corporation® that Rydapt is medically necessary when the following criteria are met:
I. Initial Approval Criteria
A. Acute Myeloid Leukemia (must meet all):

1. Diagnosis of AML;
   2. Prescribed by or in consultation with an oncologist or hematologist;
   3. Age ≥ 18 years;
   4. Positive for the FLT3 mutation;
   5. If induction therapy, prescribed in combination with cytarabine and daunorubicin;
   6. If consolidation or post-induction therapy, prescribed in combination with cytarabine;
   7. For brand Rydapt requests, member must use generic midostaurin, if available, unless contraindicated or clinically significant adverse effects are experienced;

2. Request meets one of the following (a or b): a. Dose does not exceed 100 mg (4 capsules) per day; b. Dose is supported by practice guidelines or peer-reviewed literature for the relevant off-label use (prescriber must submit supporting evidence). Prescribed regimen must be FDA-approved or recommended by NCCN Approval duration:
   Medicaid/HIM – 6 months Page 1 of 6

   CLINICAL POLICY Midostaurin Commercial – 12 months or duration of request, whichever is less
   B. Advanced Systemic Mastocytosis (must meet all):

   1. Diagnosis of one of the following (a, b, or c): a. ASM; b. SM-AHN; c. MCL;
3. Prescribed by or in consultation with an oncologist, allergist, or immunologist;
   
   3. Age ≥ 18 years;
   4. For brand Rydapt requests, member must use generic midostaurin, if available, unless contraindicated or clinically significant adverse effects are experienced;
4. Request meets one of the following (a or b): a. Dose does not exceed 200 mg (8 capsules) per day; b. Dose is supported by practice guidelines or peer-reviewed literature for the relevant off-label use (prescriber must submit supporting evidence). Prescribed regimen must be FDA-approved or recommended by NCCN Approval duration:
   Medicaid/HIM – 6 months Commercial – 12 months or duration of request, whichever is less
   C. Off-Label Indications (must meet all):
5. Diagnosis of lymphoid, myeloid or mixed lineage neoplasm with eosinophilia and FGFR1 or FLT3 rearrangements in blast or chronic phase;
6. Prescribed by or in consultation with an oncologist or hematologist;
   
   3. Age ≥ 18 years;
   4. For brand Rydapt requests, member must use generic midostaurin, if available, unless contraindicated or clinically significant adverse effects are experienced;
7. Dose is within FDA maximum limit for any FDA-approved indication or is supported by practice guidelines or peer-reviewed literature for the relevant off-label use (prescriber must submit supporting evidence).Prescribed regimen must be FDA-approved or recommended by NCCN
   Approval duration:
   Medicaid/HIM – 6 months Commercial – 12 months or duration of request, whichever is less
   D. Other diagnoses/indications (must meet 1 or 2):

8. This this drug has recently (within the last 6 months) undergone a label change (e.g., newly approved indication, age expansion, new dosing regimen) that is not yet reflected in this policy, refer to one of the following policies (a or b): a. For drugs on the formulary (commercial, health insurance marketplace) or PDL (Medicaid), the no coverage criteria policy for the relevant line of business: CP.CPA.190 for commercial, HIM.PA.33 for health insurance marketplace, and CP.PMN.255 for Medicaid; or b. For drugs NOT on the formulary (commercial, health insurance marketplace) or PDL (Medicaid), the non-formulary policy for the relevant line of business: CP.CPA.190 for commercial, HIM.PA.103 for health insurance marketplace, and CP.PMN.16 for Medicaid; or Page 2 of 6

   CLINICAL POLICY Midostaurin

9. If the requested use (e.g., diagnosis, age, dosing regimen) is NOT specifically listed under section III (Diagnoses/Indications for which coverage is NOT authorized) AND criterion 1 above does not apply, refer to the off-label use policy for the relevant line of business: CP.CPA.09 for commercial, HIM.PA.154 for health insurance marketplace, and CP.PMN.53 for Medicaid.
   II. Continued Therapy A. All Indications in Section I (must meet all):
10. Currently receiving medication via Centene benefit, or documentation supports that member is currently receiving Rydapt for a covered indication and has received this medication for at least 30 days;
11. Member is responding positively to therapy;
    3. For brand Rydapt requests, member must use generic midostaurin, if available, unless contraindicated or clinically significant adverse effects are experienced;
12. If request is for a dose increase, request meets one of the following (a, b, or c): a. AML: Dose does not exceed 100 mg (4 capsules) per day; b. ASM, SM-AHN, or MCL: Dose does not exceed 200 mg (8 capsules) per day; c. Dose is supported by practice guidelines or peer-reviewed literature for the relevant off-label use (prescriber must submit supporting evidence). Prescribed regimen must be FDA-approved or recommended by NCCN Approval duration:
    Medicaid/HIM - 12 months Commercial - 12 months or duration of request, whichever is less
    B. Other diagnoses/indications (must meet 1 or 2):
13. This this drug has recently (within the last 6 months) undergone a label change (e.g., newly approved indication, age expansion, new dosing regimen) that is not yet reflected in this policy, refer to one of the following policies (a or b): a. For drugs on the formulary (commercial, health insurance marketplace) or PDL (Medicaid), the no coverage criteria policy for the relevant line of business: CP.CPA.190 for commercial, HIM.PA.33 for health insurance marketplace, and CP.PMN.255 for Medicaid; or b. For drugs NOT on the formulary (commercial, health insurance marketplace) or PDL (Medicaid), the non-formulary policy for the relevant line of business: CP.CPA.190 for commercial, HIM.PA.103 for health insurance marketplace, and CP.PMN.16 for Medicaid; or

14. If the requested use (e.g., diagnosis, age, dosing regimen) is NOT specifically listed under section III (Diagnoses/Indications for which coverage is NOT authorized) AND criterion 1 above does not apply, refer to the off-label use policy for the relevant line of business: CP.CPA.09 for commercial, HIM.PA.154 for health insurance marketplace, and CP.PMN.53 for Medicaid.
    III. Diagnoses/Indications for which coverage is NOT authorized:
    A. Non-FDA approved indications, which are not addressed in this policy, unless there is sufficient documentation of efficacy and safety according to the off label use policies – Page 3 of 6

    CLINICAL POLICY Midostaurin CP.CPA.09 for commercial, HIM.PA.154 for health insurance marketplace, and CP.PMN.53 for Medicaid or evidence of coverage documents.
    IV. Appendices/General Information Appendix A: Abbreviation/Acronym Key AML: acute myeloid leukemia
    ASM: aggressive systemic mastocytosis FDA: Food and Drug Administration MCL: mast cell leukemia SM-AHN: systemic mastocytosis with associated hematological neoplasm Appendix B: Therapeutic Alternatives
    This table provides a listing of preferred alternative therapy recommended in the approval criteria. The drugs listed here may not be a formulary agent for all relevant lines of business and may require prior authorization.
    Drug Name Dosing Regimen AML induction therapy: cytarabine + daunorubicin AML post-remission therapy (consolidation): cytarabine Therapeutic alternatives are listed as Brand name® (generic) when the drug is available by brand name only and generic (Brand name®) when the drug is available by both brand and generic. Cytarabine 100-200 mg/m2 continuous IV infusion for 7 days with daunorubicin 60-90 mg/m2 for 3 days 3 g/m2 IV over 3 hours every 12 hours on days 1, 3, and 5 for 3 to 4 cycles Varies Dose Limit/ Maximum Dose Varies Appendix C: Contraindications/Boxed Warnings • Contraindication(s): Hypersensitivity to midostaurin or any of the excipients. • Boxed warning(s): None reported. V. Dosage and Administration
    Indication AML ASM, SM-AHN, MCL Dosing Regimen 50 mg PO BID with food 100 mg PO BID with food Maximum Dose 100 mg/day 200 mg/day VI. Product Availability
    Capsules: 25 mg VII.