Last Review Date: 11/05/2024

Date of Origin: 09/19/2017

Dates Reviewed: 09/2017, 11/2018, 11/2019, 12/2019, 07/2020, 11/2020, 11/2021, 11/2022, 11/2023, 11/2024

1. Length of Authorization ^1,5-8,11

Newly-Diagnosed AML

• In combination with daunorubicin and cytarabine (adult): Coverage will be provided for 6 months consisting of 3 cycles (1 induction and 2 consolidation) and may NOT be renewed.
• In combination with daunorubicin and cytarabine (pediatric): Coverage will be provided for 6 months consisting of 2 cycles (1 induction and 1 consolidation) and may NOT be renewed.
• In combination with idarubicin and cytarabine (adult) as induction therapy: Coverage will be provided for 6 months consisting of 1 cycle (3 doses) and may NOT be renewed.
• In combination with high-dose cytarabine (adult) as consolidation therapy: Coverage will be provided for 6 months consisting of 2 cycles (2 doses) and may NOT be renewed.   
• Single-agent therapy: Coverage will be provided for 6 months and may be renewed. Coverage is provided for 1 cycle of induction and up to a maximum of 8 cycles of continuation.

Relapsed or Refractory AML

• Coverage will be provided for 6 months consisting of 1 cycle (3 doses) and may NOT be renewed.

Acute Promyelocytic Leukemia (APL)

• Induction/Consolidation Therapy: Coverage will be provided for 6 months and may be renewed. Coverage is provided for 1 cycle of induction therapy followed by consolidation therapy. [Note: Duration of consolidation therapy is dependent on disease risk severity (see below)]
  • Low-risk disease: Coverage will be provided until achievement of complete molecular response.
  • High-risk disease: Coverage will be provided until molecular complete response.
• Therapy for first relapse:
  • Single-agent therapy: Coverage will be provided for 6 total doses
  • Use in combination with arsenic trioxide: Coverage will be provided for 6 months and may be renewed until bone marrow confirmation of remission.
• Therapy for leukocytosis associated with differentiation syndrome:
  • Coverage will be provided for one cycle (up to 3 total doses) and may NOT be renewed.

2. Dosing Limits

1. Quantity Limit (max daily dose) [NDC Unit]:

• Mylotarg 4.5 mg single-dose vial: 7 vials per initial 28 days; 6 vials per 28 days thereafter

2. Max Units (per dose and over time) [HCPCS Unit]:

• AML:

• Induction: 135 billable units on Day 1, 90 billable units on Day 4, 90 billable units on Day 7 of a 28-day cycle (1 cycle only)
• Consolidation/Continuation: 225 billable units every 28 days

• APL:

• Induction: 180 billable units on Day 1
• Consolidation/Relapse: 270 billable units every 28 days

3. Initial Approval Criteria ¹

Coverage is provided in the following conditions:

• Patient is at least 18 years of age (unless otherwise specified); AND
• Patient has not previously received gemtuzumab ozogamicin; AND
• Baseline electrocardiogram (ECG) has been obtained in patients with a history of or predisposition for QTc prolongation; AND

Universal Criteria ¹

• Patient has CD33-positive disease; AND

Acute Myeloid Leukemia (AML) † ‡ Ф ^1,6,10

• Patient has newly-diagnosed disease; AND
  • Used in combination with daunorubicin and cytarabine †; AND
    • Patient is at least 1 month of age; OR
  • Used as a single agent †; OR
  • Used in combination with cytarabine and idarubicin; AND
    • Used as induction therapy; AND
    • Patient has favorable or intermediate-risk AML; OR
  • Used in combination with high-dose cytarabine; AND
    • Used as consolidation therapy; AND
    • Patient has favorable-risk AML; OR
• Patient has relapsed or refractory disease; AND
  • Used as a single agent †; AND
    • Patient is at least 2 years of age; OR
  • Used as a component of repeating the initial successful induction regimen if ≥12 months since induction regimen; OR
• Patient has acute promyelocytic leukemia (APL); AND
  • Used for low-risk disease (white blood cell count ≤10 x 10⁹/L); AND
    • Used as induction or consolidation therapy; AND
      • Used in combination with tretinoin (ATRA); AND
      • Arsenic is not available or is contraindicated; OR
  • Used for high-risk disease (white blood cell count >10 x 10⁹/L); AND
    • Used as induction therapy; AND
      • Used in combination with tretinoin (ATRA) with or without arsenic trioxide (ATO); OR
    • Used as consolidation therapy; AND
      • Used in combination with tretinoin (ATRA) or arsenic trioxide (ATO); OR
  • Used for first relapse (morphologic or molecular); AND
    • Used as a single agent; AND
      • Used for early relapse (<6 months) after tretinoin (ATRA) and arsenic trioxide (ATO); OR
    • Used in combination with ATO (with or without ATRA); AND
      • Patient has no prior exposure to ATO; OR
      • Used for early relapse (<6 months) after an ATRA + anthracycline-containing regimen; OR
      • Used for late relapse (≥ 6 months) after an ATO containing regimen; OR
  • Used for leukocytosis associated with differentiation syndrome; AND
    • Used as a single agent for difficult-to-treat cases

† FDA Approved Indication(s); ‡ Compendium Recommended Indication(s); Ф Orphan Drug

4. Renewal Criteria ^1,6

Coverage may be renewed based upon the following criteria:

• Patient continues to meet the universal and indication-specific relevant criteria such as concomitant therapy requirements (not including prerequisite therapy), performance status, etc. identified in section III; AND
• Disease stabilization or improvement as evidenced by a complete response [CR] (i.e., morphologic, cytogenetic or molecular complete response CR), complete hematologic response or a partial response by CBC, bone marrow cytogenic analysis, QPCR, or FISH; AND
• Absence of unacceptable toxicity from the drug. Examples of unacceptable toxicity include: severe infusion-related reactions (including anaphylaxis), hemorrhage, hepatotoxicity (e.g., veno-occlusive liver disease [VOD], sinusoidal obstruction syndrome [SOS], etc.), QT interval prolongation, etc.; AND
  • Patients receiving single-agent treatment for newly-diagnosed AML have not exceeded the maximum of 8 cycles of continuation (adult only); OR
  • Patients receiving consolidation therapy for acute promyelocytic leukemia (APL):
    • Low-risk disease: Therapy will be discontinued once there is achievement of complete molecular response; OR
    • High-risk disease: Therapy will be discontinued once there is achievement of molecular complete remission; OR
  • Patients receiving therapy for first relapse of acute promyelocytic leukemia (APL):
    • Single-agent treatment: Coverage will be provided for 6 total doses
    • In combination with ATO (with or without ATRA): Therapy will be discontinued once there is bone marrow confirmation of remission; OR
  • Patients receiving therapy for leukocytosis associated with differentiation syndrome:
    • Coverage may NOT be renewed

Note: treatment of newly diagnosed AML in combination with chemotherapy and relapsed or refractory AML may NOT be renewed.

5. Dosage/Administration ^{1,5-8,11,13,14}

6. Billing Code/Availability Information

HCPCS Code:

• J9203 – Injection, gemtuzumab ozogamicin, 0.1 mg; 1 billable unit = 0.1 mg

NDC:

• Mylotarg 4.5 mg single-dose vial: 00008-4510-xx

7. References

1. Mylotarg [package insert]. Philadelphia, PA; Pfizer Inc.; August 2021. Accessed October 2024.
2. 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. Lancet. 2012 Apr 21;379(9825):1508-16
3. Amadori S, Suciu S, Selleslag D, et al. Gemtuzumab Ozogamicin Versus Best Supportive Care in Older Patients With Newly Diagnosed Acute Myeloid Leukemia Unsuitable for Intensive Chemotherapy: Results of the Randomized Phase III EORTC-GIMEMA AML-19 Trial. J Clin Oncol. 2016 Mar 20;34(9):972-9.
4. Taksin AL, Legrand O, Raffoux E, et al. High efficacy and safety profile of fractionated doses of Mylotarg as induction therapy in patients with relapsed acute myeloblastic leukemia: A prospective study of the ALFA group. Leukemia 2007;21:66–71.
5. Abaza Y, Kantarjian H, Garcia-Mannero G, et al. Long-term outcome of acute promyelocytic leukemia treated with all-transretinoic acid, arsenic trioxide, and gemtuzumab. Blood 2017;129:1275-1283.
6. Referenced with permission from the NCCN Drugs & Biologics Compendium (NCCN Compendium®) Acute Myeloid Leukemia. Version 3.2024. National Comprehensive Cancer Network, 2024. The NCCN Compendium® is a derivative work of the NCCN Guidelines®. NATIONAL COMPREHENSIVE CANCER NETWORK®, NCCN®, and NCCN GUIDELINES® are trademarks owned by the National Comprehensive Cancer Network, Inc. To view the most recent and complete version of the Compendium, go online to NCCN.org. Accessed October 2024.
7. Burnett AK, Hills RK, Milligan D, et al. Identification of patients with acute myeloblastic leukemia who benefit from the addition of gemtuzumab ozogamicin: results of the MRC AML15 trial. J Clin Oncol. 2011 Feb 1;29(4):369-77. doi: 10.1200/JCO.2010.31.4310. Epub 2010 Dec 20.
8. Hills RK, Castaigne S, Appelbaum FR, et al. Addition of gemtuzumab ozogamicin to induction chemotherapy in adult patients with acute myeloid leukaemia: a meta-analysis of individual patient data from randomised controlled trials. Lancet Oncol. 2014 Aug;15(9):986-96. doi: 10.1016/S1470-2045(14)70281-5. Epub 2014 Jul 6.
9. Gamis AS, Alonzo TA, Meshinchi S, et al. Gemtuzumab ozogamicin in children and adolescents with de novo acute myeloid leukemia improves event-free survival by reducing relapse risk: results from the randomized phase III Children’s Oncology Group trial AAML0531. J Clin Oncol. 2014;32(27):3021-3032. doi:10.1200/JCO.2014.55.3628.
10. Referenced with permission from the NCCN Drugs & Biologics Compendium (NCCN Compendium®) gemtuzumab ozogamicin. National Comprehensive Cancer Network, 2024. The NCCN Compendium® is a derivative work of the NCCN Guidelines®. NATIONAL COMPREHENSIVE CANCER NETWORK®, NCCN®, and NCCN GUIDELINES® are trademarks owned by the National Comprehensive Cancer Network, Inc. To view the most recent and complete version of the Compendium, go online to NCCN.org. Accessed October 2024.
11. Estey EH, Giles FJ, Beran M, et al. Experience with gemtuzumab ozogamycin ("mylotarg") and all-trans retinoic acid in untreated acute promyelocytic leukemia. Blood. 2002 Jun 1;99(11):4222-4. doi: 10.1182/blood-2001-12-0174. PMID: 12010830.
12. Lo-Coco F, Cimino G, Breccia M, et al. Gemtuzumab ozogamicin (Mylotarg) as a single agent for molecularly relapsed acute promyelocytic leukemia. Blood. 2004 Oct 1;104(7):1995-9.
13. Referenced with permission from the NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines®) for Gemtuzumab ozogamicin: Acute Myeloid Leukemia Chemotherapy Order Template, AML88. National Comprehensive Cancer Network, 2024. NATIONAL COMPREHENSIVE CANCER NETWORK®, NCCN®, and NCCN GUIDELINES® are trademarks owned by the National Comprehensive Cancer Network, Inc. To view the most recent and complete version of the Guidelines, go online to NCCN.org. Accessed October 2024.
14. Larson R. (2024) Acute myeloid leukemia: Induction therapy in medically fit adults. UptoDate. Last updated: Dec 13, 2023. Accessed: October 2024. Available from https://www.uptodate.com/contents/acute-myeloid-leukemia-induction-therapy-in-medically-fit-adults?sectionName=Gemtuzumab%20ozogamicin&search=gemtuzumab%20leukocytosis&topicRef=4522&anchor=H3717141861&source=see_link#H3717141861.

Appendix 1 – Covered Diagnosis Codes

Appendix 2 – Centers for Medicare and Medicaid Services (CMS)

The preceding information is intended for non-Medicare coverage determinations. Medicare coverage for outpatient (Part B) drugs is outlined in the Medicare Benefit Policy Manual (Pub. 100-2), Chapter 15, §50 Drugs and Biologicals. In addition, National Coverage Determinations (NCDs) and/or Local Coverage Determinations (LCDs) may exist and compliance with these policies is required where applicable. Local Coverage Articles (LCAs) may also exist for claims payment purposes or to clarify benefit eligibility under Part B for drugs which may be self-administered. The following link may be used to search for NCD, LCD, or LCA documents: https://www.cms.gov/medicare-coverage-database/search.aspx. Additional indications, including any preceding information, may be applied at the discretion of the health plan.

Medicare Part B Covered Diagnosis Codes (applicable to existing NCD/LCD/LCA): N/A