vp-0320
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Mylotarg (gemtuzumab ozogamicin) (Intravenous)

Policy Number: VP-0320

Last Review Date: 10/26/2020

Date of Origin: 09/19/2017

Dates Reviewed: 09/2017, 11/2018, 11/2019, 12/2019, 07/2020, 11/2020

FOR PEEHIP Members Only -Coverage excludes the provider-administered medication(s) outlined in this drug policy from being accessed through a specialty pharmacy. It must be obtained through buy and bill.

I. Length of Authorization

Newly-Diagnosed AML

  • De novo disease 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.
  • De novo disease 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.
  • Single-agent use: 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.

Post-Remission Therapy for AML

  • Coverage will be provided for 6 months consisting of 2 cycles (2 doses) and may not be renewed.

Relapsed or Refractory AML

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

Acute Promyelocytic Leukemia

  • Induction/Consolidation 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 7 cycles of consolidation.
  • Therapy after first relapse: Coverage will be provided for 6 months and may be renewed until bone marrow confirmation of remission.

II. Dosing Limits

  1. Quantity Limit (max daily dose) [NDC Unit]:
  • Mylotarg 4.5 mg vial: 5 vials per initial 28 days; 1 vial per 28 days thereafter
  1. Max Units (per dose and over time) [HCPCS Unit]:

Induction (1 cycle only)

Consolidation

AML

  • 135 billable units on Day 1 & 90 billable units on Day 8 of a 28-day cycle; OR
  • 45 billable units on Days 1, 4, & 7 of a 28-day cycle
  • 45 billable units on Day 1 of a 28-day cycle (up to a maximum of 8 subsequent cycles)

APL

180 billable units on Day 1

  • 180 billable units on Day 1 of a 28-day cycle

III. Initial Approval Criteria 

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) obtained in patients with a history of or predisposition for QTc prolongation; AND

Universal Criteria 

  • Patient has CD33-positive disease; AND

Acute Myeloid Leukemia (AML) † Ф 

  • Patient has newly-diagnosed disease; AND
    • Used in combination with daunorubicin and cytarabine; AND
      • Patient has de novo disease ; AND
        • Patient is 1 month or older; OR
      • Patient has favorable or intermediate-risk cytogenetics; OR
    • Used as a single agent ; OR
  • Used as post-remission therapy; AND
    • Used in combination with daunorubicin and intermediate-dose cytarabine; AND
      • Patient is ≥ 60 years old and obtained a complete response to previous intensive therapy; OR
      • Patient is < 60 years old with core binding factor (CBF) cytogenetic translocations without KIT mutations, or intermediate-risk cytogenetics and/or molecular abnormalities; OR
    • Used in combination with high-dose cytarabine; AND
      • Patient is < 60 years old with core binding factor (CBF) cytogenetic translocations without KIT mutations; OR
  • Patient has relapsed or refractory disease; AND
    • Used as a single agent ; AND
      • Patient is 2 years or older; OR
    • Used as a component of repeating the initial successful induction regimen if late relapse (≥12 months since induction regimen); OR
  • Patient has acute promyelocytic leukemia ; AND
    • Used as induction and consolidation therapy in patients with high risk disease (white blood cell count >10 X 109/L); AND
      • Used in combination with tretinoin (ATRA) and/or arsenic trioxide (ATO); OR
    • Used for first relapse (morphologic or molecular) in combination with arsenic trioxide (ATO); AND
      • Used for late relapse (≥ 6 months) of initial response after an arsenic trioxide (ATO) containing regimen; OR
      • Used for early relapse (<6 months) after tretinoin (ATRA) + anthracycline-containing regimen; OR
      • Patient is arsenic trioxide (ATO)-naïve

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

IV. Renewal Criteria 

Coverage can be renewed based upon the following criteria:

  • Patient continues to meet 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 the following: severe infusion-related reactions, hemorrhage, hepatotoxicity including hepatic veno-occlusive disease (VOD)/sinusoidal obstruction syndrome (SOS), 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) have not exceeded the maximum of 7 cycles of therapy; OR
    • Patients receiving therapy for first relapse of acute promyelocytic leukemia (APL): Therapy will be discontinued once there is bone marrow confirmation of remission

Note: treatment of newly diagnosed de novo AML, relapsed or refractory AML, and post-remission therapy for AML are not renewable.

V. Dosage/Administration 

Indication

Dose

Acute Myeloid Leukemia

Newly Diagnosed AML

Adult (≥ 18 years old) – Combination regimen (De Novo AML):

  • Induction Therapy (1 cycle only):
    • 3 mg/m2 (up to one 4.5 mg vial) on Days 1, 4, and 7 in combination with daunorubicin and cytarabine
    • For patients requiring a second induction cycle, do not administer gemtuzumab ozogamicin during the second induction cycle
  • Consolidation Therapy (maximum of 2 cycles):
    • 3 mg/m2 (up to one 4.5 mg vial) on Day 1 in combination with daunorubicin and cytarabine

Pediatric (1 month to < 18 years old) – Combination regimen (De Novo AML):

  • Induction Therapy (1 cycle only):
    • 3 mg/m2 (BSA ≥ 0.6 m2) or 0.1 mg/kg (BSA < 0.6 m2) on Day 6 in combination with daunorubicin and cytarabine
    • For patients requiring a second induction cycle, do not administer gemtuzumab ozogamicin during the second induction cycle
  • Consolidation/Intensification Therapy (1 cycle only):
    • 3 mg/m2 (BSA ≥ 0.6 m2) or 0.1 mg/kg (BSA < 0.6 m2) on Day 7 in Intensification 2

Single-agent regimen:

  • Induction Therapy (1 cycle only):
    • 6 mg/m2 as a single agent on Day 1, and 3 mg/m2 on Day 8
  • Continuation Therapy (maximum of 8 cycles):
    • 2 mg/m2 as a single agent on Day 1 every 4 weeks

Post-Remission Therapy for AML

Combination regimen:

  • 3 mg/m2 (up to one 4.5 mg vial) on day 1 in combination with daunorubicin and cytarabine (2 cycles only)
  • 3 mg/m2 (up to one 4.5 mg vial) on day 1 in combination with high-dose cytarabine (2 cycles only)

Relapsed or Refractory AML (single agent)

  • 3 mg/m2 (up to one 4.5 mg vial) on Days 1, 4, and 7 (1 cycle only)

Acute Promyelocytic Leukemia

Combination regimen:

  • Induction Therapy (1 cycle only):
    • 6-9 mg/m2 on Day 1 in combination with ATRA+ATO
  • Consolidation Therapy (up to a maximum of 7 cycles):
    • ATRA and ATO are used for consolidation. If ATRA or ATO are discontinued due to toxicity then: Mylotarg, single agent, dosed at 9mg/m2 on Day 1 every 4-5 weeks until 28 weeks from complete remission
  • Therapy for First Relapse
    • 6-9 mg/m2 on Day 1 in combination with ATO until count recovery with marrow confirmation of remission

VI. 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

VII. References

  1. Mylotarg [package insert]. Philadelphia, PA; Pfizer Inc., June 2020. Accessed October 2020.
  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 3.2020. National Comprehensive Cancer Network, 2020. 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 2020.
  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. Palmetto GBA, LLC. Local Coverage Article (LCA): Billing and Coding: Chemotherapy (A56141). Centers for Medicare & Medicaid Services, Inc. Updated on 05/26/2020 with effective date 04/30/2020. Accessed October 2020.

Appendix 1 – Covered Diagnosis Codes

ICD-10

ICD-10 Description

C92.00

Acute myeloblastic leukemia not having achieved remission

C92.01

Acute myeloblastic leukemia in remission

C92.02

Acute myeloblastic leukemia in relapse

C92.40

Acute promyelocytic leukemia not having achieved remission

C92.41

Acute promyelocytic leukemia in remission

C92.42

Acute promyelocytic leukemia in relapse

C92.50

Acute myelomonocytic leukemia not having achieved remission

C92.51

Acute myelomonocytic leukemia in remission

C92.52

Acute myelomonocytic leukemia in relapse

C92.60

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

C92.61

Acute myeloid leukemia with 11q23-abnormality in remission

C92.62

Acute myeloid leukemia with 11q23-abnormality in relapse

C92.A0

Acute myeloid leukemia with multilineage dysplasia not having achieved remission

C92.A1

Acute myeloid leukemia with multilineage dysplasia in remission

C92.A2

Acute myeloid leukemia with multilineage dysplasia in relapse

C93.00

Acute monoblastic/monocytic leukemia not having achieved remission

C93.01

Acute monoblastic/monocytic leukemia in remission

C93.02

Acute monoblastic/monocytic leukemia in relapse

C94.00

Acute erythroid leukemia not having achieved remission

C94.01

Acute erythroid leukemia in remission

C94.02

Acute erythroid leukemia in relapse

C94.20

Acute megakaryoblastic leukemia not having achieved remission

C94.21

Acute megakaryoblastic leukemia in remission

C94.22

Acute megakaryoblastic leukemia in relapse

     

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

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 Determination (NCD), Local Coverage Determinations (LCDs), and Local Coverage Articles (LCAs) may exist and compliance with these policies is required where applicable. They can be found at: http://www.cms.gov/medicare-coverage-database/search/advanced-search.aspx. Additional indications may be covered at the discretion of the health plan.

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

Jurisdiction(s): J & M

NCD/LCD/LCA Document (s): A56141

https://www.cms.gov/medicare-coverage-database/details/article-details.aspx?articleId=57249&ver=2&DocID=A56141&bc=gAAAABAAAAAA&

Medicare Part B Administrative Contractor (MAC) Jurisdictions

Jurisdiction

Applicable State/US Territory

Contractor

E (1)

CA, HI, NV, AS, GU, CNMI

Noridian Healthcare Solutions, LLC

F (2 & 3)

AK, WA, OR, ID, ND, SD, MT, WY, UT, AZ

Noridian Healthcare Solutions, LLC

5

KS, NE, IA, MO

Wisconsin Physicians Service Insurance Corp (WPS)

6

MN, WI, IL

National Government Services, Inc. (NGS)

H (4 & 7)

LA, AR, MS, TX, OK, CO, NM

Novitas Solutions, Inc.

8

MI, IN

Wisconsin Physicians Service Insurance Corp (WPS)

N (9)

FL, PR, VI

First Coast Service Options, Inc.

J (10)

TN, GA, AL

Palmetto GBA, LLC

M (11)

NC, SC, WV, VA (excluding below)

Palmetto GBA, LLC

L (12)

DE, MD, PA, NJ, DC (includes Arlington & Fairfax counties and the city of Alexandria in VA)

Novitas Solutions, Inc.

K (13 & 14)

NY, CT, MA, RI, VT, ME, NH

National Government Services, Inc. (NGS)

15

KY, OH

CGS Administrators, LLC