Centene midostaurin (Rydapt) Coverage Update

Coverage and Medical Necessity Criteria

Initial Therapy - AML

Covered when ALL of the following are met

AML initial approval: 1. Diagnosis of acute myeloid leukemia (AML). 2. Prescribed by or in consultation with an oncologist or hematologist. 3. Age ≥ 18 years. 4. Documented presence of an FLT3 mutation (detected by an FDA-approved test). 5. If used for induction: prescribed in combination with cytarabine and either daunorubicin or idarubicin. 6. If used for consolidation: prescribed in combination with cytarabine. 7. If used for maintenance (off-label): prescribed as a single agent AND one of the following: (i) member is post-allogeneic hematopoietic cell transplantation and in remission; OR (ii) member previously received a FLT3 inhibitor and does not have an allogeneic hematopoietic cell transplantation planned. 8. For brand Rydapt requests, member must use generic midostaurin if available unless contraindicated or clinically significant adverse effects occur. 9. Request meets one of the following: (a) dose does not exceed 100 mg (4 capsules) per day; OR (b) dose is supported by practice guidelines or peer-reviewed literature for the relevant off-label use with submitted supporting evidence.age >=18; FLT3 mutation positive

Prescribed regimen must be FDA-approved or recommended by NCCN

Initial Therapy - Systemic Mastocytosis

Covered when ALL of the following are met

Systemic Mastocytosis initial approval: 1. Diagnosis of one of the following: aggressive systemic mastocytosis (ASM), systemic mastocytosis with associated hematologic neoplasm (SM-AHN), mast cell leukemia (MCL), indolent systemic mastocytosis (ISM) (off-label), smoldering systemic mastocytosis (SSM) (off-label), or well-differentiated systemic mastocytosis (WDSM) (off-label). 2. Prescribed by or in consultation with an oncologist, allergist, or immunologist. 3. Age ≥ 18 years. 4. Prescribed as a single agent. 5. For ISM or SSM: disease is symptomatic AND failure of one of the following: (i) participation in a clinical trial (unless not available); OR (ii) for ISM only, prior trial of avapritinib (Ayvakit®) unless contraindicated, clinically significant adverse effects occurred, or platelets < 50 x 10^9/L. 6. For WDSM: member has advanced systemic mastocytosis (excluding chronic MCL), disease is KIT D816V–negative, AND next-generation sequencing reveals no alternate (non–exon 17) KIT mutation in exons 8–11. 7. For brand Rydapt requests, member must use generic midostaurin if available unless contraindicated or clinically significant adverse effects occur. 8. Request meets one of the following: (a) dose does not exceed 200 mg (8 capsules) per day; OR (b) dose is supported by practice guidelines or peer-reviewed literature for the relevant off-label use with submitted supporting evidence.age >=18

Prescribed regimen must be FDA-approved or recommended by NCCN

Initial Therapy - Myeloid/Lymphoid Neoplasm (off-label)

Covered when ALL of the following are met

Myeloid/Lymphoid neoplasm initial approval: 1. Diagnosis of a lymphoid, myeloid, or mixed phenotype neoplasm with eosinophilia and FGFR1 or FLT3 rearrangements in blast or chronic phase. 2. 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 occur. 5. Dose is within the 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).age >=18

Prescribed regimen must be FDA-approved or recommended by NCCN

Continuation Therapy

Continuation of therapy (renewal) covered when ALL of the following are met

Continuation of therapy: 1. Member is currently receiving midostaurin via the Centene benefit, or documentation supports that the member has been receiving midostaurin for a covered indication for at least 30 days. 2. 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 occur. 4. If request is for a dose increase, the new dose must meet one of the following: (a) AML: new dose does not exceed 100 mg (4 capsules) per day; (b) ASM, SM-AHN, or MCL: new dose does not exceed 200 mg (8 capsules) per day; (c) new 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

Covered indications (summary)

Policy covers midostaurin when used for NCCN-supported indications and select off-label uses added per NCCN guidance.

NCCN-supported AML indications: Includes induction therapy in combination with cytarabine plus daunorubicin or idarubicin for FLT3-mutated AML; may be used as maintenance therapy, including for patients who previously received a FLT3 inhibitor and are not planned for allogeneic hematopoietic cell transplantation per NCCN.

Added across 2Q2024 and 2Q2025 reviews

Systemic mastocytosis indications: Includes systemic mastocytosis (ASM, SM-AHN, MCL) and expanded off-label use in ISM, SSM, and WDSM per NCCN; Rydapt must be prescribed as a single agent for systemic mastocytosis per policy update.

Added/expanded in 2Q2024–2Q2026 reviews

Myeloid/lymphoid neoplasms with eosinophilia: Includes use in blast or chronic phase for myeloid/lymphoid neoplasms with eosinophilia and FGFR1 or FLT3 rearrangements per NCCN guidance.

Referenced in prior reviews (2Q2022)

Coverage for non‑FDA‑approved indications of midostaurin (Rydapt) that are not explicitly addressed in this policy is not authorized unless the provider submits sufficient documentation demonstrating efficacy and safety. Such documentation should follow applicable off‑label use policies: CP.CPA.09 for Commercial lines of business, HIM.PA.154 for Health Insurance Marketplace/ICHRA, and CP.PMN.53 for Medicaid, or other relevant evidence of coverage documents.

Administrative updates to prior versions have retired legacy templates and consolidated approval durations across lines of business. Historically, initial approval durations and continuation lengths were adjusted (for example, a prior consolidation to 6 months initial and 12 months continuation was documented); current policy language reflects those administrative consolidations and unified duration handling across applicable business lines.

There are no explicit conditions labeled as "not medically necessary" in the provided policy excerpts. Denial considerations and exclusions are described elsewhere (e.g., non‑FDA indications without supporting documentation) but no distinct list of not‑medically‑necessary scenarios is provided in these chunks.

Authorization, Documentation, and Provider Requirements

Prior Authorization

Prior Authorization Required

Prior authorization is required. Provider must submit documentation (office chart notes, lab results, mutation testing, treatment regimen, and specialist consultation) supporting that the member meets all approval criteria. Lack of submitted documentation may lead to denial.

Diagnosis and indication per policy
Age and specialist documented (e.g., oncologist, hematologist, allergist, or immunologist as applicable)
Mutation status: FLT3 positive required for AML; KIT D816V and/or NGS results as specified for mastocytosis subtypes
Prescribed regimen details (drug, dose, combination agents, therapy phase: induction/consolidation/maintenance)

Note

Prior Authorization and Approval Duration

Initial approvals have defined durations by line of business. Commercial: 12 months or duration of request, whichever is less. Medicaid/HIM/ICHRA: 12 months. Continuation durations and historical consolidation to 6 months initial/12 months continuation referenced in policy history.

Billing and Coding References

Codes referencedmixed

NDC and billing codes not provided in these chunks

No explicit CPT/HCPCS/ICD-10/NDC codes listed in provided document sections

Dosing, Regimens, and Administration

Indication	Regimen / Dose	Maximum daily dose	Coverage status
Acute Myeloid Leukemia (AML)	50 mg orally twice daily with food	100 mg/day	Covered with criteria (see AML coverage criteria)

Indication	Regimen / Dose	Maximum daily dose	Coverage status
Aggressive systemic mastocytosis (ASM), Systemic mastocytosis with associated hematologic neoplasm (SM-AHN), Mast cell leukemia (MCL)	100 mg orally twice daily with food	200 mg/day	Covered with criteria (see systemic mastocytosis coverage criteria)

Indication	Regimen	Combination agents	Coverage status
Acute Myeloid Leukemia (FLT3‑mutated) — induction	Midostaurin administered per regimen in combination with induction chemotherapy	Cytarabine plus daunorubicin or idarubicin	Covered when ALL AML induction criteria are met (see coverage criteria)

Indication	Regimen	Administration	Coverage status
Systemic mastocytosis (ASM, SM‑AHN, MCL, and select off‑label ISM/SSM/WDSM per NCCN)	Midostaurin as a single agent	Administered per labeled dosing (see indication-specific dose limits); Rydapt must be prescribed as a single agent for systemic mastocytosis per policy update	Covered with criteria (see systemic mastocytosis coverage criteria)

Permitted Lines of Therapy

first-line

First-line: Induction: midostaurin prescribed in combination with cytarabine plus daunorubicin or idarubicin for FLT3‑mutated AML per NCCN.

salvage

Salvage: Use allowed in blast or chronic phase for myeloid/lymphoid neoplasms with eosinophilia and FGFR1 or FLT3 rearrangements (off‑label), prescribed by or in consultation with an oncologist or hematologist.

first-line | maintenance

First-line (induction): May be prescribed with cytarabine plus daunorubicin or idarubicin for induction in FLT3‑mutated AML per NCCN (added 2Q2024).

Biomarker and Diagnostic Test Requirements

inv-25: FLT3 — detected by an FDA-approved test

BiomarkerFLT3 mutation detected by an FDA-approved test

Required for indicationDiagnosis of AML must be FLT3 mutation–positive

Testing responsibilityPrescriber must document mutation status in prior authorization submission

inv-26: KIT D816V and KIT exons 8-11 — biomarker requirement entries

Required biomarkersKIT D816V status and KIT exons 8-11 sequencing (NGS)

WDSM specific requirementMember must be KIT D816V–negative and NGS must reveal no alternate (non‑exon 17) KIT mutation in exons 8–11

Acronyms and Definitions

inv-19: AML — acute myeloid leukemia

DefinitionAML: acute myeloid leukemia

AbbreviationAML is abbreviated as 'AML' in policy appendices

Age requirementPolicy specifies age ≥ 18 years for AML coverage

inv-20: ASM — aggressive systemic mastocytosis

DefinitionASM: aggressive systemic mastocytosis

Related diagnosesIncludes ASM, SM‑AHN, and MCL per policy; ISM/SSM/WDSM listed as off‑label/systemic mastocytosis subtypes

Age requirement

Background and Drug Overview

Midostaurin (Rydapt) is an oral kinase inhibitor referenced in this policy for hematologic malignancies. It is indicated for use in FLT3‑mutated acute myeloid leukemia (AML)—administered in combination with cytarabine plus daunorubicin or idarubicin for induction and with cytarabine for consolidation—and for systemic mastocytosis subtypes including aggressive systemic mastocytosis (ASM), systemic mastocytosis with associated hematologic neoplasm (SM‑AHN), and mast cell leukemia (MCL). The policy also incorporates NCCN‑aligned expansions and select off‑label uses (for example, indolent, smoldering, and well‑differentiated systemic mastocytosis per later updates) and references midostaurin dosing and regimen considerations consistent with these indications.

OpenPayer

Midostaurin (Rydapt) coverage

Coverage and Medical Necessity Criteria

Authorization, Documentation, and Provider Requirements

Billing and Coding References

Dosing, Regimens, and Administration

Permitted Lines of Therapy

Biomarker and Diagnostic Test Requirements

Acronyms and Definitions

Background and Drug Overview