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09-J2000-86

Original Effective Date: 09/15/17

Reviewed: 08/09/17

Revised: 10/01/17

Next Review: 011/08/18

Subject: Midostaurin (Rydapt)

THIS MEDICAL COVERAGE GUIDELINE IS NOT AN AUTHORIZATION, CERTIFICATION, EXPLANATION OF BENEFITS, OR A GUARANTEE OF PAYMENT, NOR DOES IT SUBSTITUTE FOR OR CONSTITUTE MEDICAL ADVICE. ALL MEDICAL DECISIONS ARE SOLELY THE RESPONSIBILITY OF THE PATIENT AND PHYSICIAN. BENEFITS ARE DETERMINED BY THE GROUP CONTRACT, MEMBER BENEFIT BOOKLET, AND/OR INDIVIDUAL SUBSCRIBER CERTIFICATE IN EFFECT AT THE TIME SERVICES WERE RENDERED. THIS MEDICAL COVERAGE GUIDELINE APPLIES TO ALL LINES OF BUSINESS UNLESS OTHERWISE NOTED IN THE PROGRAM EXCEPTIONS SECTION.

           
Dosage/ Administration Position Statement Billing/Coding Reimbursement Program Exceptions Definitions
           
Related Guidelines Other References Updates  
           

DESCRIPTION:

Midostaurin (Rydapt) is an orally administered drug that inhibits multiple receptor tyrosine kinases. Inhibition of FLT3 (FMS-like tyrosine kinase 3) receptor signaling and cell proliferation induces apoptosis in leukemic cells expressing mutant FLT3 receptors or overexpressing wild type FLT3 and PDGF receptors. Midostaurin also inhibits KIT signaling, cell proliferation and histamine release and induces apoptosis in mast cells. Midostaurin was approved by the US Food and Drug Administration (FDA) in April 2017 “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 a FDA approved test”, and for “the treatment of adult patients with aggressive systemic mastocytosis (ASM), systemic mastocytosis with associated hematological neoplasm (SM-AHN), or mast cell leukemia (MCL).” Midostaurin was previously granted orphan designation by the FDA for the treatment of AML in 2009 and for the treatment of mastocytosis in 2010. Midostaurin is the first new drug to be FDA-approved and available for treatment of AML since 1990 (i.e., the approval of idarubicin).

Acute myeloid leukemia is a hematological malignancy characterized by the clonal expansion of myeloid blasts in the peripheral blood, bone marrow, and/or other tissues. It is the most common form of acute leukemia among adults, and accounts for the largest number of annual deaths from leukemia in the US. The median age of diagnosis is 67 years. A diagnosis is typically made based on the presence of 20% myeloid blast in the marrow or peripheral blood. Assessment of molecular abnormalities (KIT, FLT3, NPM1, CEBPA, and other mutation) has become important for risk assessment, prognostication, and treatment selection. The FLT3 gene encodes a receptor tyrosine kinase involved in hematopoiesis. Two major classes of activating FLT3 mutations have been identified in patients with AML- internal tandem duplications (ITD), ~30% of AML patients, and tyrosine kinase domain (TKD) point mutations, ~10% AML patients. Patients with a FLT3-ITD mutation, as opposed to wild-type FLT3, typically have shorter remission durations and poorer survival outcomes. Patients with a FLT3-TKD mutation may also have worse outcomes, but the risk impact is less clear. Treatment of AML is divided into induction chemotherapy and postremission (e.g., consolidation) therapy. Initial treatment decisions are primarily based on age (<60 or ≥60), history of prior myelodysplasia or cytotoxic therapy, and performance status. Candidates for intensive remission induction therapy typically receive a regimen based on a backbone of cytarabine plus an anthracycline (daunorubicin or idarubicin). Up to two courses of inpatient induction therapy may be attempted to induce a complete response. If a complete response is achieved, consolidation therapy normally consists of cytarabine for 3 or 4 cycles (inpatient or outpatient). An allogeneic hematopoietic stem cell transplantation (HSCT) can be considered for induction failures and as a consolidation option for patient with unfavorable-risk cytogenetics and/or molecular abnormalities. For patients with FTL3-mutated AML, midostaurin can be given during induction and consolidation chemotherapy, and for up to 12 months of maintenance treatment.

The National Comprehensive Cancer Network (NCCN) clinical practice guidelines for AML (Version 3.2017) list midostaurin as a category 2A treatment option for patients with FTL3-mutated disease in the following induction regimen: standard-dose cytarabine 200 mg/m2 continuous infusion X 7 days with daunorubicin 60 mg/m2 X 3 days and oral midostaurin 50 mg every 12 hours, days 8 to 21. This regimen is listed for patients aged <60 years and for patients ≥60 years who are candidates for intensive remission induction therapy. Following a complete response to induction or re-induction, NCCN lists midostaurin as a category 2A treatment option in the following consolidation regimen: high-dose cytarabine 3 g/m2 over 3 hours every 12 hours on days 1, 3, 5 for 3 to 4 cycles. In both age groups the regimens include a footnote stating, “While midostaurin was not FDA-approved for maintenance therapy, the study was designed for consolidation and maintenance midostaurin for a total of 12 months.” For patient aged ≥60 years, there is an additional footnote of, “The RATIFY trial studies patients aged 18 to 60 years. An extrapolation of the data suggests that older patients who are fit to received 7 + 3 should be offered midostaurin since it seems to provide a survival benefit without undue toxicity.” Of note, for relapsed/refractory disease in patients with a FLT3-ITD mutation, the NCCN lists a hypomethylating agent [azacitidine (Vidaza) or decitabine (Dacogen)] + sorafenib (Nexavar) as a treatment option. Midostaurin is only recommended for previously untreated disease, but can be used in both FLT3-ITD and FLT3-TKD mutations.

The safety and efficacy of midostaurin leading to FDA-approval for the treatment of AML was assessed in a randomized, double-blind, placebo-controlled trial (CALGB 10603/RATIFY) of adult patients aged 18 to 59 years with newly-diagnosed, FLT3-mutated AML. The FLT3 mutation status was determined prospectively with a clinical trial assay and verified retrospectively using the companion diagnostic LeukoStrat CDx FLT3 Mutation Assay. Patients were randomized to receive midostaurin 50 mg twice daily (n=360) or placebo (n=357) with food on Days 8 to 21 in combination with daunorubicin (60 mg/m2 daily on Days 1 to 3) and cytarabine (200 mg/m2 daily on Days 1 to 7) for up to two cycles of induction, high-dose cytarabine (3 g/m2 every 12 hours on Days 1, 3 and 5) for up to four cycles of consolidation, followed by continuous midostaurin or placebo treatment for up to 12 additional 28-day cycles. Patients who proceeded to HSCT stopped receiving study treatment. Baseline demographics include median age of 48 years, 44% male, and 88% with a performance status of 0 or 1. A second course of induction was administered to 25% of the patients, 62% initiated at least one cycle of consolidation, 29% initiated maintenance, and 17% completed all 12 planned cycles of maintenance. The overall rate of HSCT was 57%. After a median follow-up of 59 months, midostaurin plus standard chemotherapy was superior to placebo plus standard chemotherapy in overall survival (HR 0.78; 95% CI 0.63, 0.96; p=0.009). When median overall survival (OS) was assessed without censoring HSCT patients, midostaurin significantly increased OS vs. placebo (74.7 months vs. 25.6 months; p=0.009). The 4-year OS rate was 51.4% in the midostaurin group and 44.3% in the placebo group. Median OS could not yet be determined when HSCT patients were censored. The median event-free survival (EFS) [failure to obtain a complete remission (CR) within 60 days of initiation of protocol therapy, or relapse, or death from any cause] was also improved with midostaurin (8.2 months vs. 3 months; HR 0.78, 95% CI 0.66, 0.93; p=0.005)

Mastocytosis refers to a group of disorders characterized by excessive mast cell accumulation in one or multiple tissues, and can be subdivided into two primary group: cutaneus mastocytosis (CM) or systemic mastocytosis (SM). Children are usually affected by cutaneous forms and most improve or resolve by adolescence. Adults more often present with systemic forms of mastocytosis and have persistent disease. Greater than 95% of adults with SM have activating exon 17 KIT mutations, most commonly D816V. Systemic mastocytosis is further divided into five clinical subtypes: indolent systemic mastocytosis (ISM), smoldering systemic mastocytosis (SSM), systemic mastocytosis with an associated hematologic neoplasm (SM-AHN), aggressive systemic mastocytosis (ASM), and mast cell leukemia (MCL). Clinical manifestations of SM include skin findings, symptoms due to the release of mast cell mediators, and symptoms arising from mast cell infiltration of organs. The clinical manifestations of organ infiltration (known as C-findings) include cytopenias, skeletal lesions, hepatomegaly, liver impairment, protal hypertension, splenomegaly, and weight lost due to gastrointestinal involvement. Patients with ISM and SSM usually have an indolent course, with median survival measured in decades. However, ASM, SM-AHN, and MCL have a more aggressive course, with median survival of 3.5 year, 2 year, and 6 months, respectively. Cytoreductive therapy is indicated in patients with advanced subtypes of SM to mitigate organ dysfunction and improve quality of life. Allogeneic HSCT offers the potential for cure in patients responding to therapy, but there is substantial risk of transplant-related mortality. Prior to midostaurin, imatinib was the only FDA-approved treatment for ASM, but treatment is only effective in patients without a D816V c-Kit mutation (~10% of cases).

The safety and efficacy of single-agent midostaurin for the treatment of systemic mastocytosis was assessed in a two single-arm, open-label, multicenter trials (D2201 and A2213) in adult patients with ASM, SM-AHN, and MCL (i.e., advanced SM). The primary efficacy study (D2201) enrolled 116 adult patients with relapse or progression on 0, 1, or 2 prior regimens for SM. The study excluded patients with acute-stage or life-threatening associated hematologic neoplasms. Patients received midostaurin 100 mg orally twice daily in 28-day cycles until disease progression or intolerable toxicity. Of the 116 patients treated, the study steering committee identified 89 patients who had measurable C-findings and were evaluable for response (ASM=16, SM-AHN=57, and MCL=16). The median age in this group was 64 years, 64% of patients were male, nearly all patients (97%) were white, 36% had prior therapy for SM, and 82% had the KIT D816V mutation detected at baseline. The primary outcome was best overall response, as assessed by the modified Valent response criteria, which occurred in the first six 4-week treatment cycles and was maintained for at least 8 weeks. The overall response rate (ORR) represents the percentage of patients whose best overall response was a major response (defined as complete resolution of ≥1 C-finding) or a partial response (defined as >50% improvement in ≥1 C-finding [good partial response] or as >20% to ≤50% improvement in ≥1 C-finding [minor partial response]). The major findings are presented in Table 1.

Table 1: Primary Efficacy Results from D2201 Study

 

Overall
Response Rate

Duration of Response (median)

Overall Survival

Progression-free Survival

Systemic mastocytosis (any subtype)

60% (45% major response; 15% partial response)

24.1 months

28.7 months

14.1 months

ASM

75%

Not reached

Not reached

28.7 months

SM-AHN

58%

12.7 months

20.7 months

11 months

MCL

50%

Not reached

9.4 months

11.3 months

POSITION STATEMENT:

Comparative Effectiveness

The FDA has deemed the drug(s) or biological product(s) in this coverage policy to be appropriate for self-administration or administration by a caregiver (i.e., not a healthcare professional). Therefore, coverage (i.e., administration) in a provider-administered setting such as an outpatient hospital, ambulatory surgical suite, physician office, or emergency facility is not considered medically necessary.

Initiation of midostaurin (Rydapt) meets the definition of medical necessity when used for either of the following indications (“1” or “2”) AND all associated criteria are met:

1. Member has a confirmed diagnosis of acute myeloid leukemia (AML) and ALL of the following are met (“a”, “b”, “c”, “d”):

a. Member has newly-diagnosed disease

b. Member has FLT3 (FMS-like tyrosine kinase 3) mutation-positive disease – laboratory documentation of a FLT3-ITD (internal tandem duplication) or FLT3-TKD (tyrosine kinase domain) mutation must be submitted [i.e., ratio of mutant to wild-type alleles of at least 0.05]

c. Treatment with midostaurin will be used in combination with standard-dose cytarabine (200 mg/m2/day for 7 days) and daunorubicin (60 mg/m2/day for 3 days) induction chemotherapy, and cytarabine consolidation chemotherapy

d. The dosage of midostaurin does not exceed either of the following:

i. During induction and consolidation chemotherapy - 50 mg (two 25 mg capsules) twice daily on days 8 to 21 (i.e., 2 weeks) of each 28-day cycle

ii. Maintenance therapy following induction and consolidation – 50 mg (two 25 mg capsules) twice daily

2. Member has a confirmed diagnosis of advanced systemic mastocytosis (SM) and ALL of the following are met: (“a”, “b”, and “c”):

a. The member has one of the following subtypes of advanced SM – the confirmatory bone marrow biopsy results must be submitted

i. Aggressive systemic mastocytosis (ASM)

ii. Systemic mastocytosis with associated hematologic neoplasm (SM‐AHN)

iii. Mast cell leukemia (MCL)

b. Midostaurin will NOT be used in combination with other cytoreductive therapies (e.g., cladribine, imatinib, interferon-alpha)

c. The dosage of midostaurin does not exceed 100 mg (four 25 mg capsules) twice daily

Approval duration: 6 months

Continuation of midostaurin (Rydapt) meets the definition of medical necessity when EITHER of the following criteria is met (“1” or “2”) based on the indication for treatment:

1. Members with a diagnosis of AML and all the following are met:

a. An authorization for midostaurin has been previously approved by Florida Blue in the past 12 months, OR the member has previously met ALL indication-specific initiation criteria

b. The member achieved and has maintained a complete response (CR) following induction and consolidation chemotherapy

c. The member has not received a hematopoietic stem cell transplantation (HSCT) for treatment of their AML

d. Midostaurin will be used a monotherapy during maintenance treatment (i.e., treatment following induction and consolidation with chemotherapy)

e. The dosage of midostaurin does not exceed either of the following:

i. During induction and consolidation chemotherapy - 50 mg (two 25 mg capsules) twice daily on days 8 to 21 (i.e., 2 weeks) of each 28-day cycle

ii. Maintenance therapy following induction and consolidation – 50 mg (two 25 mg capsules) twice daily

f. The member will not receive and has not received more than 12 consecutive months of maintenance treatment

2. Members with a diagnosis of advanced systemic mastocytosis and all the following are met:

a. An authorization or reauthorization for midostaurin has been previously approved by Florida Blue in the past 12 months, OR the member has previously met ALL indication-specific initiation criteria

b. The member has not experienced disease progression during midostaurin treatment

c. Midostaurin will NOT be used in combination with other cytoreductive therapies (e.g., cladribine, imatinib, interferon-alpha)

d. The dosage of midostaurin does not exceed 100 mg (four 25 mg capsules) twice daily

Approval duration: 1 year

Midostaurin (Rydapt) does NOT meet the definition of medically necessity for the following indications:

• Acute promyelocytic leukemia (APL)

• Cutaneous mastocytosis and associated subtypes

• Indolent systemic mastocytosis (ISM)

• Smoldering systemic mastocytosis (SSM)

DOSAGE/ADMINISTRATION:

THIS INFORMATION IS PROVIDED FOR INFORMATIONAL PURPOSES ONLY AND SHOULD NOT BE USED AS A SOURCE FOR MAKING PRESCRIBING OR OTHER MEDICAL DETERMINATIONS. PROVIDERS SHOULD REFER TO THE MANUFACTURER’S FULL PRESCRIBING INFORMATION FOR DOSAGE GUIDELINES AND OTHER INFORMATION RELATED TO THIS MEDICATION BEFORE MAKING ANY CLINICAL DECISIONS REGARDING ITS USAGE.

FDA-approved

Acute Myeloid Leukemia - 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 a FDA approved test

o The recommended dose is 50 mg orally twice daily with food on Days 8 to 21 (i.e., 2 weeks) of each cycle of induction with cytarabine and daunorubicin and on Days 8 to 21 of each cycle of consolidation with high-dose cytarabine. In the clinical trial continuous single-agent maintenance treatment with midostaurin beyond induction and consolidation was permitted for up to 12 additional 28-day cycles. Treatment with midostaurin is to be stopped once a patient proceeds to hematopoietic stem cell transplantation. In the study, only 29% of patients initiated maintenance, and only 17% completed all 12 planned cycles of maintenance.

Systemic Mastocytosis - for the treatment of adult patients with aggressive systemic mastocytosis (ASM), systemic mastocytosis with associated hematological neoplasm (SM-AHN), or mast cell leukemia (MCL)

o The recommended dose is 100 mg orally twice daily with food. Continue treatment until disease progression or unacceptable toxicity occurs. Monitor patients for toxicity at least weekly for the first 4 weeks, every other week for the next 8 weeks, and monthly thereafter while on treatment.

• Administer prophylactic anti-emetics before treatment with midostaurin to reduce the risk of nausea and vomiting. Administer midostaurin orally with food, twice daily at approximately 12 hour intervals. Do not open or crush the capsules.

Dose Adjustments

• Table 1 in the product labeling provides recommendations for dose modifications in patients with ASM, SM-AHN, and MCL for neutropenia, thrombocytopenia, anemia, grade 3 or 4 nausea and/or vomiting, and other grade 3 or 4 non-hematological toxicities. In most cases, treatment is interrupted and then resumed at 50 mg twice daily. If tolerated, the dose is then increased back to 100 mg twice daily. Treatment should be discontinued if adverse effects persist despite the lower 50 mg dosage.

Drug Availability

• 25 mg soft capsules in a carton containing either 56 capsules [two inner packs each with 28 capsules (7 blister cards with 4 capsules each )] or 112 capsules [four inner packs each with 28 capsules (7 blister cards with 4 capsules each)]

PRECAUTIONS:

Boxed Warning

• None

Contraindications

• Patients with hypersensitivity to midostaurin or to any of the excipients

Precautions/Warnings

Embryo-fetal Toxicity: Midostaurin may cause fetal harm when administered to a pregnant woman. In animal studies, midostaurin caused embryo-fetal toxicities, including late embryo-fetal death and reduced fetal birth weight, with delays in fetal growth at doses lower than the recommended human dose. Advise pregnant women of the potential risk to the fetus. Verify the pregnancy status of females of reproductive potential within 7 days prior to initiating therapy. Advise females of reproductive potential to use effective contraception during treatment and for at least 4 months after the last dose. Advise males with female partners to use effective contraception during treatment and for 4 months after the last dose.

Pulmonary Toxicity: Cases of interstitial lung disease and pneumonitis, some fatal, have occurred in patients treated with midostaurin as monotherapy or with chemotherapy. Monitor for symptoms of interstitial lung disease or pneumonitis. Discontinue midostaurin in patients with signs or symptoms of pulmonary toxicity.

CYP3A4 Drug Interactions: Coadministration of midostaurin with strong CYP3A inhibitors (e.g., clarithromycin, diltiazem, grapefruit juice, ketoconazole, ritonavir) may increase midostaurin concentrations and the risk of toxicity. Consider alternative therapies that do not strongly inhibit CYP3A activity, or, if concurrent use is unavoidable, monitor patients for increased risk of adverse reactions, especially during the first week of administration. Coadministration of midostaurin with strong CYP3A inducers (e.g., carbamazepine, enzalutamide, phenytoin, rifampin, St. John’s wort) may decrease midostaurin concentrations and reduce efficacy. Avoid coadministration with strong CYP3A4 inducers.

BILLING/CODING INFORMATION:

The following codes may be used to describe:

HCPCS Coding

J8999

Prescription drug, oral, chemotherapeutic, NOS

ICD-10 Diagnoses Codes That Support Medical Necessity

C92.00

Acute myeloblastic leukemia not having achieved remission

C92.01

Acute myeloblastic leukemia in remission

C92.50

Acute myelomonocytic leukemia not having achieved remission

C92.51

Acute myelomonocytic leukemia in remission

C92.60

Acute myeloid leukemia with 11q23-abnormality not having achieved remission

C92.61

Acute myeloid leukemia with 11q23-abnormality in remission

C92.A0

Acute myeloid leukemia with multilineage dysplasia not having achieved remission

C92.A1

Acute myeloid leukemia with multilineage dysplasia in remission

C93.00

Acute monoblastic/monocytic leukemia not having achieved remission

C93.01

Acute monoblastic/monocytic leukemia in remission

C94.00

Acute erythroid leukemia not having achieved remission

C94.01

Acute erythroid leukemia in remission

C94.20

Acute megakaryoblastic leukemia not having achieved remission

C94.21

Acute megakaryoblastic leukemia in remission

C94.30

Mast cell leukemia not having achieved remission

C94.31

Mast cell leukemia in remission

C94.32

Mast cell leukemia in relapse

C96.21

Aggressive systemic mastocytosis

C96.29

Other malignant mast cell neoplasm

REIMBURSEMENT INFORMATION:

Refer to section entitled POSITION STATEMENT.

PROGRAM EXCEPTIONS:

Federal Employee Program (FEP): Follow FEP guidelines.

State Account Organization (SAO): Follow SAO guidelines.

Medicare Part D: BCBSF has delegated to Prime Therapeutics authority to make coverage determinations for the Medicare Part D services referenced in this guideline.

Medicare Advantage: No National Coverage Determination (NCD) and/or Local Coverage Determination (LCD) were found at the time of guideline creation.

DEFINITIONS:

None

RELATED GUIDELINES:

Allogeneic Bone Marrow and Stem Cell Transplantation, 02-38240-01

Azacitidine (Vidaza) Injection, 09-J0000-84

Granulocyte Colony Stimulating Factors, 09-J0000-62

Imatinib (Gleevec) Tablets, 09-J1000-46

Sorafenib (Nexavar) Tablets, 09-J1000-50

Topotecan HCl (Hycamtin) Injection and Capsule, 09-J1000-02

OTHER:

WHO Diagnostic Criteria for Systemic Mastocytosis

The diagnosis can be made when the major criterion and one minor criterion or at least three minor criteria are present

Major criterion:

• Multifocal, dense infiltrates of mast cells (≥15 mast cells in aggregates) detected in sections of bone marrow and/or other extracutaneous organ(s)

Minor criteria:

1. In biopsy sections of bone marrow or other extracutaneous organs, >25% of the mast cells in the infiltrate are spindle-shaped or have atypical morphology or, of all mast cells in bone marrow aspirate smears, >25% are immature or atypical.

2. Detection of an activating point mutation at codon 816 of KIT in bone marrow, blood, or another extracutaneous organ.

3. Mast cells in bone marrow, blood, or other extracutaneous organs express CD2 and/or CD25 in addition to normal mast cell markers.

4. Serum total tryptase persistently exceeds 20 ng/mL (unless there is an associated clonal myeloid disorder, in which case this parameter is not valid).

REFERENCES:

  1. Arber DA, Orazi A, Hasserjian R, et al. The 2016 revision to the World Health Organization classification of myeloid neoplasms and acute leukemia. Blood. 2016;127(20):2391.
  2. Clinical Pharmacology [database online]. Tampa, FL: Gold Standard, Inc.; 2017. Available at: www.clinicalpharmacilogy-ip.com. Accessed 7/19/17.
  3. Fischer T, Stone RM, Deangelo D, et al. Phase IIB trial of oral Midostaurin (PKC412), the FMS-like tyrosine kinase 3 receptor (FLT3) and multi-targeted kinase inhibitor, in patients with acute myeloid leukemia and high-risk myelodysplastic syndrome with either wild-type or mutated FLT3. J Clin Oncol. 2010 Oct 1;28(28):4339-45.
  4. Gotlib J, Kluin-Nelemans HC, George TI, et al: Efficacy and safety of midostaurin in advanced systemic mastocytosis. N Engl J Med. 2016; 374(26):2530-2541.
  5. Horny HP, Metcalfe DD, Bennett JM, et AL. Mastocytosis. In: World Health Organization Classification of tumours of haematopoietic and lymphoid tissues, Swerdlow SH, Campo E, Harris NL, et al (Eds), IARC Press, Lyon 2008.
  6. Micromedex Healthcare Series [database online]. Greenwood Village, Colo: Thomson Healthcare; 2017. Accessed 7/19/17,
  7. Muppidi MR, Portwood S, Griffiths EA, et al. Decitabine and Sorafenib Therapy in FLT-3 ITD-Mutant Acute Myeloid Leukemia. Clin Lymphoma Myeloma Leuk. 2015 Jun;15 Suppl:S73-9.
  8. National Comprehensive Cancer Network. Cancer Guidelines. Cancer Guidelines and Drugs and Biologics Compendium. Accessed 7/19/17.
  9. National Comprehensive Cancer Network. NCCN clinical practice guidelines in oncology (NCCN Guidelines). Acute Myeloid Leukemia (Version 3.2017) [cited 2017 Jul 19]. Available from: http://www.nccn.org/professionals/physician_gls/f_guidelines.asp.
  10. Orphan Drug Designations and Approval [Internet]. Silver Spring (MD): US Food and Drug Administration; 2017 [cited Jul 2017]. Available from: http://www.accessdata.fda.gov/scripts/opdlisting/oopd/index.cfm/
  11. Ravandi F, Alattar ML, Grunwald MR, et al. Phase 2 study of azacytidine plus sorafenib in patients with acute myeloid leukemia and FLT-3 internal tandem duplication mutation. Blood. 2013 Jun 6;121(23):4655-62.
  12. Rydapt (midostaurin) [prescribing information]. Novartis. East Hanover, NJ. April 2017.
  13. Stone RM, Fischer T, Paquette R, et al. Phase IB study of the FLT3 kinase inhibitor midostaurin with chemotherapy in younger newly diagnosed adult patients with acute myeloid leukemia. Leukemia. 2012 Sep;26(9):2061-8.
  14. Stone RM, Mandrekar S, Sanford BL, et al. Midostaurin plus Chemotherapy for Acute Myeloid Leukemia with a FLT3 Mutation. N Engl J Med. 2017 Jun 23. doi: 10.1056/NEJMoa1614359. [Epub ahead of print].

COMMITTEE APPROVAL:

This Medical Coverage Guideline (MCG) was approved by the BCBSF Pharmacy Policy Committee on 08/09/17.

GUIDELINE UPDATE INFORMATION:

09/15/17

New Medical Coverage Guideline.

10/01/17

New ICD-10 codes.

Date Printed: October 20, 2017: 12:03 PM