Subject:
Gemtuzumab Ozogamicin (Mylotarg)
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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Mylotarg®, or gemtuzumab ozogamicin, is a CD-33 directed antibody-drug conjugate. Mylotarg® is indicated for the treatment of newly-diagnosed CD33 positive acute myeloid leukemia (AML) in adults and in relapsed or refractory CD33 positive AML in adults and in pediatric patients 2 years of age and older. Mylotarg® works by inducing double-strand DNA breaks, subsequently inducing cell cycle arrest and apoptotic cell death in cancer cells.
The safety and efficacy of Mylotarg® for treatment of newly diagnosed CD33 positive AML were evaluated in the ALFA-0701 clinical trial, a multicenter, randomized, open-label study. 271 patients with newly-diagnosed previously untreated AML ages 50 to 70 were enrolled. Patients needed to have normal cardiac function. CD33 antigen was not required for inclusion. Patients were not eligible if they had previous myeloproliferative or myelodysplastic syndrome or exposure to chemotherapy or radiotherapy, CNS involvement, uncontrolled infection, and liver (ALT/AST > 2.5 X ULN, serum bilirubin > 2 X ULN) or renal (Scr > 2.5 ULN) dysfunction. Patients received daunorubicin (60mg/m2 on days 1 to 3) and cytarabine (200 mg/m2 on days 1 to 7) with or without Mylotarg® 3 mg/m2 on days 1, 4, and 7. If patient did experience a response after the first induction, determined by > 10% persistent leukemic blasts, they could receive a second induction cycle with daunorubicin and cytarabine alone. If patients did respond, they received 2 rounds of consolidation therapy with daunorubicin and cytarabine with or without Mylotarg®. Efficacy was based on event-free survival (EFS). The median EFS was 17.3 months in the Mylotarg® group versus 9.5 months in the control arm. Treatment induced neutropenia was longer in the Mylotarg® group after the first and second consolidation cycles. Additionally, duration of thrombocytopenia was significantly longer after each treatment. Persistent grade 3 and 4 thrombocytopenia occurred in 3% of the control group and 16% of the Mylotarg® group. Three patients developed veno-occlusive disease, two of which died. Grade 3 and 4 adverse hematological and non-hematological adverse events were increased in the Mylotarg® group.
The safety and efficacy were also studied in Study AML-19, a multicenter- randomized, open-label study that compared Mylotarg® to best supportive care for patients that had newly-diagnosed previously untreated AML who were ineligible for intensive chemotherapy. Patients were ineligible because they were either over 75 years or 61 to 75 with a ECOG score greater than 2 or were unwilling to receive chemotherapy. Patients had serum creatinine and liver levels within 1.5 times the upper limit of normal, and white blood cell counts < 30 X 109/L. 236 patients were enrolled in the trial. Patients were excluded if they had acute promyelocytic leukemia, blast transformation of a chronic myeloproliferative disorder, central nervous system leukemia, prior treatment for AML or antecedent myelodysplasia, concomitant malignant disease, severe organ dysfunction, uncontrolled infection, and HIV. If patients were receiving Mylotarg®, they received induction therapy with 6 mg/m2 on day 1 and 3 mg/m2 on day 8. If patients had no evidence of disease progression or significant toxicities after induction therapy, they received continuation therapy as outpatients with up to 8 courses of Mylotarg® 2mg/m2 on Day 1 every 4 weeks. Mylotarg® showed an improvement in overall survival, with a HR of 0.69. Median overall survival was 4.9 months with Mylotarg® versus 3.6 months in the best supportive care arm. No patients develop veno-occlusive disease in this trial, however, grade > 3 AE’s were slightly increased in the Mylotarg® group. Rates of non-hematologic AE’s, grade > 3 AE’s and AE’s with death as an outcome were similar between the treatment groups.
The safety and efficacy of Mylotarg® for relapsed or refractory CD33 positive AML was studied in the MyloFrance-1 trial. This is a phase 2, single-arm, open-label study in adults with CD33 positive AML in first relapse. Patients received a single course of Mylotarg® 3mg/m2 on Days 1, 4, and 7. Consolidation therapy was cytarabine 3 g/m2 every 12 hours for 3 days. 57 patients were treated with Mylotarg®. Patients ranged from 22 to 80 years of age. 44% had intermediate risk and 22% had poor risk cytogenetics. The median duration of first remission was 10 months. Efficacy was based on complete remission and the duration of remission. 26% of patients achieved complete response following single course of Mylotarg® and median duration of relapse free survival was 11.6 months.
[INFORMATIONAL NOTE: Mylotarg®packaging includes the following BLACK BOX WARNINGS:
- Hepatotoxicity, including severe or fatal hepatic veno-occlusive disease (VOD), also known as sinusoidal obstruction syndrome (SOS), has been reported in association with the use of Mylotarg.]
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Policy:
(NOTE: For Medicare Advantage, please refer to the Medicare Coverage Section below for coverage guidance.)
The requirements of the Horizon BCBSNJ Gemtuzumab Ozogamicin (Mylotarg) Program may require a precertification/prior authorization via MagellanRx Management. These requirements are member-specific: please verify member eligibility and requirements through the Horizon Provider Portal (www.horizonblue.com/provider). Ordering clinicians should request pre-certification from MagellanRx Management at ih.magellanrx.com or call 1-800-424-4508 (when applicable).
I. 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
II. Mylotarg® (gemtuzumab ozogamicin) is considered medically necessary for FDA approved indications:
A. Newly Diagnosed CD33 positive acute myeloid leukemia (AML) when all of the following criteria are met
- 1 month of age or older
- Normal cardiac function
- No previous treatment
- Baseline SCr, AST/ALT, Serum bilirubin and WBC counts
B. Relapsed or Refractory CD33 positive AML
- 2 years of age older
- First remission duration > 3 months and < 18 months
- ECOG < 2
- Baseline Scr, AST/ALT
- No prior hematopoietic stem cell transplant
[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.]
III. When Mylotarg® (gemtuzumab ozogamicin) is medically necessary, therapy will be approved for a period of 6 months at the FDA approved dose based on the indication
A. Combination regimen for newly Diagnosed CD33 positive AML
- Adults
- Treatment consists of 1 induction cycle and 2 consolidation cycles
- Induction cycles consists of Mylotarg® 3 mg/m2 (up to one 4.5 mg vial) on days 1, 4, and 7 in combination with daunorubicin and cytarabine.
- If patients require a second induction cycle, do NOT administer Mylotarg®
- Consolidation cycles consist of Mylotarg® 3 mg/m2 on Day 1 (up to one 4.5 mg vial) in combination with daunorubicin and cytarabine
- Pediatrics (1 month and older)
- Induction Therapy (1 cycle only) 3mg/m2 (BSA ≥ 0.6 m2) or 0.1 mg/kg (BSA < 0.6 m2) on Day 6 in combination with daunorubicin and cytarabine
- Consolidation/Intensification Therapy (1 cycle only) 3mg/ m2 (BSA ≥ 0.6 m2) or 0.1 mg/kg (BSA < 0.6 m2) on Day 7
B. Single-agent regimen for newly-diagnosed CD33 positive AML
- Adults
- 1 cycle of induction and up to 8 cycles of continuation therapy
- Induction cycle consists of Mylotarg® 6 mg/m2 (not limited to one 4.5 mg vial) on Day 1 and 3 mg/m2 on Day 8
- Continuation therapy consists of Mylotarg® 2 mg/m2 (not limited to one 4.5 mg vial) Day 1 every 4 weeks
C. Single-agent regimen for relapsed or refractory CD33 positive AML
- Adults and pediatrics (2 years and older)
- Treatment consists of a single course of Mylotarg® 3 mg/m2 (up to one 4.5 mg vial) on Days 1, 4, and 7.
[INFORMATIONAL NOTE: As per the FDA approved package insert, patients should be pre-medicated prior to administration of MylotargTM
- Pre-medication for adults
- Acetaminophen 650 mg and diphenhydramine 50 mg orally or intravenously 1 hour prior to MylotargTM dosing. Then, administer 1 mg/kg methylprednisolone or equivalent dose of an alternative corticosteroid within 30 minutes prior to infusion of MylotargTM. ]
- Premedication for children
- Acetaminophen 15 mg/kg (maximum of 650), diphenhydramine 1 mg/kg (maximum of 50 mg), and 1 mg/kg methylprednisolone orally or intravenously
- Additional doses of acetaminophen and diphenhydramine may be administered every 4 hours after the initial pretreatment dose. ]
IV. Continued therapy of Mylotarg® (gemtuzumab ozogamicin) beyond the FDA approved duration is considered investigational.
V. Mylotarg (gemtuzumab ozogamicin) is considered medically necessary for the off-label indications that are 2A or better recommendations on National Comprehensive Cancer Network (NCCN) compendium. Refer to National Comprehensive Cancer Network: Drugs and Biologics Compendium - [Gemtuzumab ozogamicin]. Available at: https://www.nccn.org/professionals/drug_compendium/content/.
VI. Mylotarg® (gemtuzumab ozogamicin) for the treatment of other conditions/diseases is considered investigational.
Medicare Coverage:
There is no National Coverage Determination (NCD) or Local Coverage Determination (LCD) for jurisdiction JL for this drug. Therefore, Medicare Advantage Products will follow the Horizon BCBSNJ Medical 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:
Gemtuzumab Ozogamicin (Mylotarg)
Mylotarg (Gemtuzumab Ozogamicin)
References:
1. Mylotarg® [package insert]. Pfizer. New York, NY. June 2020.
2. National Comprehensive Cancer Network (NCCN). NCCN Clinical Practice Guidelines in Oncology. Breast Cancer. Version 5.2020. 2020 July 15.; National Comprehensive Cancer Network. Available at http://www.nccn.org/professionals/physician_gls/pdf/breast.pdf.
3. Castaigne, S., et. All. (2012). Effect of gemtuzumab ozogamicin on survival of adult patients with de-novo acute myeloid leukaemia (ALFA-0701): a randomised, open-label, phase 3 study. The Lancet, 379(9825), pp.1508-1516.
4. Castaigne S, Pautas C, Terré C et al. Effect of gemtuzumab ozogamicin on survival of adult patients with de-novo acute myeloid leukaemia (ALFA-0701): a randomised, open-label, phase 3 study. The Lancet. 2012;379(9825):1508-1516. doi:10.1016/s0140-6736(12)60485-1.
5. ClinicalTrials.gov accessed July 30, 2020 at https://clinicaltrials.gov/
6. National Comprehensive Cancer Network (NCCN). NCCN Drugs & Biologics Compendium. Mylotarg. Available at https://www.nccn.org/professionals/drug_compendium/content/. Accessed July 30, 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
J9203
* 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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