Subject:
Liposomal Formulation of Daunorubicin and Cytarabine (Vyxeos)
Description:
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IMPORTANT NOTE:
The purpose of this policy is to provide general information applicable to the administration of health benefits that Horizon Blue Cross Blue Shield of New Jersey and Horizon Healthcare of New Jersey, Inc. (collectively “Horizon BCBSNJ”) insures or administers. If the member’s contract benefits differ from the medical policy, the contract prevails. Although a service, supply or procedure may be medically necessary, it may be subject to limitations and/or exclusions under a member’s benefit plan. If a service, supply or procedure is not covered and the member proceeds to obtain the service, supply or procedure, the member may be responsible for the cost. Decisions regarding treatment and treatment plans are the responsibility of the physician. This policy is not intended to direct the course of clinical care a physician provides to a member, and it does not replace a physician’s independent professional clinical judgment or duty to exercise special knowledge and skill in the treatment of Horizon BCBSNJ members. Horizon BCBSNJ is not responsible for, does not provide, and does not hold itself out as a provider of medical care. The physician remains responsible for the quality and type of health care services provided to a Horizon BCBSNJ member.
Horizon BCBSNJ medical policies do not constitute medical advice, authorization, certification, approval, explanation of benefits, offer of coverage, contract or guarantee of payment.
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Acute myeloid leukemia is a rapidly progressing cancer that originates in the bone marrow and results in an increased number of white blood cells in the blood stream. Each year, approximately 21,380 people are diagnosed with AML and 10,590 patients with AML will die in 2017 due to AML. Two types of difficult to treat AML’s exist, therapy related AML (T-AML), and AML with myelodysplasia-related changes (AML-MRC). T-AML occurs within five years in 8 to 10 percent of cancer patients who have been treated with chemotherapy or radiation. AML-MRC is characterized by certain blood disorders and other mutations within cancer cells.
VyxeosTM, a liposomal formulation of daunorubicin and cytarabine in a 1:5 molar ratio, is a treatment for T-AML and AML-MRC. Daunorubicin forms complexes with DNA and causes DNA damaging free radicals. Cytarabine works through inhibiting DNA polymerase. The fixed ratio of the two medications has been shown to have a synergistic effect in killing leukemia cells.
The safety and efficacy of VyxeosTM were evaluated in an open-label, active-controlled study which compared VyxeosTM to the combination of cytarabine and daunorubicin, known as 7+3. The study consisted of 309 patients, ages 60 to 75, with t-AML or AML-MRC. Inclusion criteria included AML diagnosed by blasts of 20% or greater in the peripheral blood or bone marrow, either therapy related AML or AML with a history of MDS or AML with history of CMMoLAML or de novo AML with karyotypic abnormalities of MDS, Eastern Cooperative Oncology Group (ECOG) performance score of 0-2, Serum creatinine < 2.0 mg/dL, total bilirubin < 2.0 mg/dL, ALT or AST < 3 X ULN, and cardiac ejection fraction > 50%, evidence of second malignancies while in remission if malignancies stable for > 6 months while off of cytotoxic therapy. Exclusion criteria included patients with history of myeloproliferative neoplasms, acute promyelocytic leukemia, evidence of active CNS leukemia, active second malignancies, prior treatment intended for induction therapy for AML, administration of any therapy for MDS, any major surgery or radiation therapy within four weeks, cumulative anthracycline exposure > 368 mg/m2 of daunorubicin, serious medical condition, myocardial impairment of any cause, active or uncontrolled infection, current fungal infection, history of Wilson’s disease or other copper-metabolism disorders. VyxeosTM was given intravenously days 1, 3, and 5 for induction and on days 1 and 3 for the second induction, if necessary. Patients also received two rounds of consolidation therapy, if necessary. VyxeosTM resulted in 9.6 months of survival versus 5.9 months in 7+3 (P=0.005). Additionally, the complete response rate was higher in the VyxeosTM treatment group versus the 7+3 (58% vs. 41%, P=0.036). At 12 months, 41.5% of VyxeosTM patients were alive, compared to 27.6% on 7+3. There were no statistically significant differences in grade 3 or higher adverse events between VyxeosTM and 7+3.
Policy:
NOTE: For Medicare Advantage, please refer to the Medicare Coverage Section below for coverage guidance)
I. VyxeosTM is considered medically necessary based on the FDA approved indication for patients with newly diagnosed therapy related acute myeloid leukemia or AML with myelodysplasia-related changes when ALL of the following criteria are met:
- The prescriber is a specialist in the area of the patient’s diagnosis (e.g. oncologist) or has consulted with a specialist in the area of the patient’s diagnosis
- Member is at least 18 years or older
- Member has ECOG performance score of 0-2
- Member has serum creatinine of < 2.0 mg/dL
- Member has total bilirubin of < 2.0 mg/dL
- Member has AST or ALT < 3.0 X ULN
- Member has cardiac ejection fraction > 50%
- Member does NOT have any of the following:
- Anthracycline exposure greater than 368 mg/m.2
- Myocardial impairment of any cause (cardiomyopathy, ischemic heart disease, significant valvular dysfunction, hypertensive heart disease, and congestive heart failure) that result in heart failure NYHA III or IV
- Hypersensitivity to cytarabine, daunorubicin or liposomal products
- History of Wilson’s disease or other copper-metabolism disorder
- Member will not be using in combination with other chemotherapy
[INFORMATIONAL NOTE: ECOG Performance Status:
- Grade 0: Fully active, able to carry on all pre-disease performance without restriction.
- Grade 1: Restricted in physically strenuous activity but ambulatory and able to carry out work of a light or sedentary nature, e.g., light house work, office work.
- Grade 2: Ambulatory and capable of all selfcare but unable to carry out any work activities; up and about more than 50% of waking hours.]
II. When VyxeosTM is medically necessary, therapy will be approved for a period of 6 months at the following FDA approved doses:
- For induction cycles administer VyxeosTM (daunorubicin 44 mg/m2 and cytarabine 100 mg/m2) liposome:
o Cycle 1 administer on days 1, 3, and 5.
o If the patient does not achieve remission, a second induction cycle can be administered on days 1 and 3.
- For consolidation cycles, administer VyxeosTM (daunorubicin 29 mg/m2 and cytarabine 65 mg/m2) liposome on days 1 and 3.
- Allow for 2 to 5 weeks between induction cycles.
- Allow for 5 to 8 weeks between the start of the last induction cycle and the start of consolidation cycles.
- Allow for 5 to 8 weeks between the start of the first consolidation cycle and the second consolidation cycle.
- A course of treatment consists of up to 2 cycles of VyxeosTM for induction followed by up to 2 additional cycles for consolidation.
[INFORMATIONAL NOTE: As per the FDA approved labeling, prophylactic anti emetics should be given prior to treatment with VyxeosTM. Calculate total exposure to anthracycline’s prior to administration. Do not start VyxeosTM consolidation until ANC recovers to > 0.5 Gi/L, platelet count > 50 Gi/L.]
III. Continuation of VyxeosTM beyond 4 cycles is considered investigational.
IV. VyxeosTM is considered medically necessary for off-label indications that have in effect a rating of ‘Category 1’ or ‘Category 2A’ in the current recommendations in the National Comprehensive Cancer Network (NCCN) compendium. Refer to National Comprehensive Cancer Network: Drugs and Biologics Compendium - VyxeosTM. Available at: https://www.nccn.org/professionals/drug_compendium/content/
V. VyxeosTM is considered investigational for all other indications, including but not limited to myelodysplastic syndrome.
Medicare Coverage
There is no National Coverage Determination (NCD) or Local Coverage Determination (LCD) for jurisdiction JL for this service. Therefore, Medicare Advantage Products will follow the Horizon Policy.
Medicaid Coverage
For Horizon NJ Health members, please follow this link for the corresponding HNJH drug policy https://services3.horizon-bcbsnj.com/ddn/NJhealthWeb.nsf
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Horizon BCBSNJ Medical Policy Development Process:
This Horizon BCBSNJ Medical Policy (the “Medical Policy”) has been developed by Horizon BCBSNJ’s Medical Policy Committee (the “Committee”) consistent with generally accepted standards of medical practice, and reflects Horizon BCBSNJ’s view of the subject health care services, supplies or procedures, and in what circumstances they are deemed to be medically necessary or experimental/ investigational in nature. This Medical Policy also considers whether and to what degree the subject health care services, supplies or procedures are clinically appropriate, in terms of type, frequency, extent, site and duration and if they are considered effective for the illnesses, injuries or diseases discussed. Where relevant, this Medical Policy considers whether the subject health care services, supplies or procedures are being requested primarily for the convenience of the covered person or the health care provider. It may also consider whether the services, supplies or procedures are more costly than an alternative service or sequence of services, supplies or procedures that are at least as likely to produce equivalent therapeutic or diagnostic results as to the diagnosis or treatment of the relevant illness, injury or disease. In reaching its conclusion regarding what it considers to be the generally accepted standards of medical practice, the Committee reviews and considers the following: all credible scientific evidence published in peer-reviewed medical literature generally recognized by the relevant medical community, physician and health care provider specialty society recommendations, the views of physicians and health care providers practicing in relevant clinical areas (including, but not limited to, the prevailing opinion within the appropriate specialty) and any other relevant factor as determined by applicable State and Federal laws and regulations.
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Index:
Liposomal Formulation of Daunorubicin and Cytarabine (Vyxeos)
Vyxeos (Liposomal Formulation of Daunorubicin and Cytarabine)
Daunorubicin and Cytarabine Liposomal Formulation (Vyxeos)
Cytarabine and Daunorubicin Liposomal Formulation (Vyxeos)
References:
1. VyxeosTM Prescribing Information. Jazz Pharmaceuticals. Dublin, Ireland. July 2019.
2. FDA approves first treatment for certain types of poor-prognosis acute myeloid leukemia. FDA News Release. U.S. Food and Drug Administration. https://www.fda.gov/NewsEvents/Newsroom/Press Announcements/ucm569883.htm. Published August 3rd, 2017. Accessed August 28th, 2017.
3. Pharmaceuticals C. Celator Announces Phase 3 Trial for Vyxeo™ (CPX-351) in Patients with High-Risk Acute Myeloid Leukemia Demonstrates Statistically Significant Improvement in Overall Survival. Cision. http://www.prnewswire.com/news-releases/celator-announces-phase-3-trial-for-vyxeos-cpx-351-in-patients-with-high-risk-acute-myeloid-leukemia-demonstrates-statistically-significant-improvement-in-overall-survival-300235620.html. Published March 14, 2016. Accessed August 28, 2017.
4. Stein EM, Tallman MS. Emerging therapeutic drugs for AML. Blood. 2016;127(1):71-8.
5. NCCN Clinical Practice Guidelines in Oncology. Acute Myeloid Leukemia. Version 3.2020. December 2019. Available at: https://www.nccn.org/professionals/physician_gls/pdf/aml.pdf. Accessed January 28, 2020.
6. ClinicalTrials.gov. Vyxeos (daunorubicin and cytarabine) Available at https://clinicaltrials.gov/ct2/results?cond=&term=vyxeos&cntry=&state=&city=&dist=. Accessed January 2020.
7. NCCN Drugs and Biologics Compendium™. Vexeos. 2020. [Available at: http://www.nccn.org/professionals/drug_compendium/MatrixGenerator/Matrix.aspx?AID=399][cited January 28, 2020.]
Codes:
(The list of codes is not intended to be all-inclusive and is included below for informational purposes only. Inclusion or exclusion of a procedure, diagnosis, drug or device code(s) does not constitute or imply authorization, certification, approval, offer of coverage or guarantee of payment.)
CPT*
HCPCS
* CPT only copyright 2020 American Medical Association. All rights reserved. CPT is a registered trademark of the American Medical Association.
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Medical policies can be highly technical and are designed for use by the Horizon BCBSNJ professional staff in making coverage determinations. Members referring to this policy should discuss it with their treating physician, and should refer to their specific benefit plan for the terms, conditions, limitations and exclusions of their coverage.
The Horizon BCBSNJ Medical Policy Manual is proprietary. It is to be used only as authorized by Horizon BCBSNJ and its affiliates. The contents of this Medical Policy are not to be copied, reproduced or circulated to other parties without the express written consent of Horizon BCBSNJ. The contents of this Medical Policy may be updated or changed without notice, unless otherwise required by law and/or regulation. However, benefit determinations are made in the context of medical policies existing at the time of the decision and are not subject to later revision as the result of a change in medical policy
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