VYXEOS (daunorubicin and cytarabine) Non-Discrimination Statement and Multi-Language Interpreter Services information are located at the end of this document. Coverage for services, procedures, medical devices and drugs are dependent upon benefit eligibility as outlined in the member's specific benefit plan. This Medical Coverage Guideline must be read in its entirety to determine coverage eligibility, if any. This Medical Coverage Guideline provides information related to coverage determinations only and does not imply that a service or treatment is clinically appropriate or inappropriate. The provider and the member are responsible for all decisions regarding the appropriateness of care. Providers should provide BCBSAZ complete medical rationale when requesting any exceptions to these guidelines. The section identified as Description defines or describes a service, procedure, medical device or drug and is in no way intended as a statement of medical necessity and/or coverage. The section identified as Criteria defines criteria to determine whether a service, procedure, medical device or drug is considered medically necessary or experimental or investigational. State or federal mandates, e.g., FEP program, may dictate that any drug, device or biological product approved by the U.S. Food and Drug Administration (FDA) may not be considered experimental or investigational and thus the drug, device or biological product may be assessed only on the basis of medical necessity. Medical Coverage Guidelines are subject to change as new information becomes available. For purposes of this Medical Coverage Guideline, the terms "experimental" and "investigational" are considered to be interchangeable. BLUE CROSS, BLUE SHIELD and the Cross and Shield Symbols are registered service marks of the Blue Cross and Blue Shield Association, an association of independent Blue Cross and Blue Shield Plans. All other trademarks and service marks contained in this guideline are the property of their respective owners, which are not affiliated with BCBSAZ. O1056.docx Page 1 of 7
Description: Vyxeos (daunorubicin and cytarabine) liposome for injection is indicated for the treatment of adults with newly diagnosed therapy-related acute myeloid leukemia (t-aml) and AML with myelodysplasia-related changes (AML-MRC). t-aml occurs as a complication of cytotoxic therapy or ionizing radiation in approximately 8-10% of all individuals treated for cancer within an average of 5 years after treatment. AML-MRC is characterized by a history of certain blood disorders and other significant mutations within cancer cells. AML is a rapidly progressing cancer that forms in the bone marrow and results in an increased number of abnormal white blood cells in the bloodstream and bone marrow. AML with Myelodysplasia-Related Changes (AML-MRC): A diagnosis of AML-MRC requires 20% blasts (in peripheral blood or bone marrow), absence of a history of prior cytotoxic therapy for an unrelated disease and one of the following three criteria: AML that progressed from myelodysplastic syndrome (MDS) or myelodysplastic/myeloproliferative neoplasm (MDS/MPN) AML with MDS-related cytogenetic abnormalities or AML with multi-lineage dysplasia ( 50% dysplastic cells in two hematopoietic lineages) Definitions: Adult: Age 18 years and older O1056.docx Page 2 of 7
Criteria: See Resources section for FDA-approved dosage. Vyxeos is considered medically necessary for an adult with documentation of ALL of the following: 1. ONE of the following: Newly-diagnosed therapy-related acute myeloid leukemia (t-aml) AML with myelodysplasia-related changes (AML-MRC) 2. Inadequate response to use of daunorubicin and cytarabine concurrently 3. Prior to initiating Vyxeos, there is verification of a negative pregnancy test in a woman of reproductive potential 4. Left ventricular ejection fraction is at least 50% by multi-gated radionuclide angiography (MUGA) scan or echocardiography 5. No signs or symptoms of acute copper toxicity 6. Creatinine clearance > 30 ml/min 7. The total bilirubin is < 3 mg/dl 8. Lifetime cumulative anthracycline exposure is calculated before each cycle and has not reached the maximum cumulative limit of 550 mg/m 2 with non-liposomal daunorubicin or 400 mg/m 2 in those who received radiation to the mediastinum 9. No history of serious hypersensitivity to daunorubicin, cytarabine, or any component of the formulation Continuation of Vyxeos is considered medically necessary with documentation of ALL of the following: 1. No unacceptable or unmanageable toxicity from Vyxeos (daunorubicin and cytarabine) 2. No disease progression O1056.docx Page 3 of 7
Criteria: (cont.) Vyxeos for all other indications not previously listed or if above criteria not met is considered experimental or investigational based upon: 1. Lack of final approval from the Food and Drug Administration, and 2. Insufficient scientific evidence to permit conclusions concerning the effect on health outcomes, and 3. Insufficient evidence to support improvement of the net health outcome, and 4. Insufficient evidence to support improvement of the net health outcome as much as, or more than, established alternatives, and 5. Insufficient evidence to support improvement outside the investigational setting. These indications include, but are not limited to: Treatment with dosing or frequency outside the FDA-approved dosing and frequency Resources: Literature reviewed 04/09/18. We do not include marketing materials, poster boards and nonpublished literature in our review. 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. May 19 2016;127(20):2391-2405. 2. National Comprehensive Cancer Network. NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines ). Acute Myeloid Leukemia. Version 1.2018 - February 7, 2018. O1056.docx Page 4 of 7
Resources: (cont.) Vyxeos Package Insert: - FDA-approved indication and dosage: Indication VYXEOS is a liposomal combination of daunorubicin, an anthracycline topoisomerase inhibitor, and cytarabine, a nucleoside metabolic inhibitor that is indicated for the treatment of adults with newly-diagnosed therapy-related acute myeloid leukemia (t-aml) or AML with myelodysplasia-related changes (AML- MRC). Advise females and males of reproductive potential to use effective contraception during treatment and for 6 months following the last dose of VYXEOS. Women should not breastfeed during treatment with VYXEOS and for at least 2 weeks after the last dose Recommended Dose For intravenous use only, delivered as a constant infusion via an infusion pump through a central venous catheter or peripherally inserted central catheter. VYXEOS has different dosage recommendations than daunorubicin hydrochloride injection, cytarabine injection, daunorubicin citrate liposome injection, and cytarabine liposome injection. Verify drug name and dose prior to preparation and administration to avoid dosing errors. Prior to initiation of each cycle, calculate the prior cumulative anthracycline (daunorubicin or other) exposure. Cumulative exposure of Daunorubicin per cycle: Therapy Daunorubicin per dose #Doses per cycle Daunorubicin per cycle 1 st Induction cycle 44 mg/m 2 3 132 mg/m 2 2 nd Induction cycle 44 mg/m 2 2 88 mg/m 2 Each Consolidation cycle 29 mg/m 2 2 58 mg/m 2 A full course consists of 1-2 cycles of induction and up to 2 cycles of consolidation. Administer prophylactic anti-emetics before treatment. Induction: VYXEOS (daunorubicin 44 mg/m 2 and cytarabine 100 mg/m 2 ) liposome via intravenous infusion over 90 minutes on days 1, 3, and 5 and if needed, on days 1 and 3 for subsequent cycles of induction. The second induction cycle, if needed, should be administered 2-5 weeks after the first induction cycle. Consolidation: VYXEOS (daunorubicin 29 mg/m 2 and cytarabine 65 mg/m 2 ) liposome via intravenous infusion over 90 minutes on days 1 and 3. The first consolidation cycle should be administered 5-8 weeks after the start of the last induction. Initial Approval Duration: 6 months Renewal Approval Duration: 12 months O1056.docx Page 5 of 7
Non-Discrimination Statement: Blue Cross Blue Shield of Arizona (BCBSAZ) complies with applicable Federal civil rights laws and does not discriminate on the basis of race, color, national origin, age, disability or sex. BCBSAZ provides appropriate free aids and services, such as qualified interpreters and written information in other formats, to people with disabilities to communicate effectively with us. BCBSAZ also provides free language services to people whose primary language is not English, such as qualified interpreters and information written in other languages. If you need these services, call (602) 864-4884 for Spanish and (877) 475-4799 for all other languages and other aids and services. If you believe that BCBSAZ has failed to provide these services or discriminated in another way on the basis of race, color, national origin, age, disability or sex, you can file a grievance with: BCBSAZ s Civil Rights Coordinator, Attn: Civil Rights Coordinator, Blue Cross Blue Shield of Arizona, P.O. Box 13466, Phoenix, AZ 85002-3466, (602) 864-2288, TTY/TDD (602) 864-4823, crc@azblue.com. You can file a grievance in person or by mail or email. If you need help filing a grievance BCBSAZ s Civil Rights Coordinator is available to help you. You can also file a civil rights complaint with the U.S. Department of Health and Human Services, Office for Civil Rights electronically through the Office for Civil Rights Complaint Portal, available at https://ocrportal.hhs.gov/ocr/portal/lobby.jsf, or by mail or phone at: U.S. Department of Health and Human Services, 200 Independence Avenue SW., Room 509F, HHH Building, Washington, DC 20201, 1 800 368 1019, 800 537 7697 (TDD). Complaint forms are available at http://www.hhs.gov/ocr/office/file/index.html Multi-Language Interpreter Services: O1056.docx Page 6 of 7
Multi-Language Interpreter Services: (cont.) O1056.docx Page 7 of 7