Clinical Policy: Mitoxantrone

Reference Number: CP.PHAR.258
Effective Date: 08.01.16
Last Review Date: 05.26
Line of Business: Commercial, HIM/ICHRA, Medicaid

[ Coding Implications ](Coding Implications)
[ Revision Log ](Revision Log)

See Important Reminder at the end of this policy for important regulatory and legal information.

Description

Mitoxantrone is a synthetic antineoplastic anthracenedione.

FDA Approved Indication(s)

Mitoxantrone is indicated for:

• Reducing neurologic disability and/or the frequency of clinical relapses in patients with secondary (chronic) progressive, progressive relapsing, or worsening relapsing-remitting multiple sclerosis (MS) (i.e., patients whose neurologic status is significantly abnormal between relapses)
• Treatment of patients with pain related to advanced hormone-refractory prostate cancer as initial chemotherapy in combination with corticosteroids
• Initial therapy of acute nonlymphocytic leukemia (ANLL) (including myelogenous, promyelocytic, monocytic, and erythroid acute leukemias) in adults in combination with other approved drug(s)

Limitation(s) of use: Mitoxantrone is not indicated in the treatment of patients with primary progressive MS.

Policy/Criteria

Approval duration:
Medicaid/HIM/ICHRA – 12 months
Commercial – 6 months or to the member’s renewal date, whichever is longer

C. Acute Nonlymphocytic Leukemia (must meet all):

1. Diagnosis of ANLL (including myelogenous [i.e., acute myelogenous leukemia], promyelocytic, monocytic, and erythroid acute leukemias);
2. Prescribed by or in consultation with an oncologist or hematologist;
3. Age ≥ 18 years;
4. Mitoxantrone is prescribed in combination with other therapies for the diagnosis;
5. Request meets one of the following (a or b):
   a. Dose does not exceed 12 mg/m² per infusion;
   b. Dose is supported by practice guidelines or peer-reviewed literature for the relevant off-label use (prescriber must submit supporting evidence);
   Prescribed regimen must be FDA-approved or recommended by NCCN.
6. Total cumulative lifetime dose does not exceed 140 mg/m².
   Approval duration:
   Medicaid/HIM/ICHRA – 12 months
   Commercial – 6 months or to the member’s renewal date, whichever is longer

D. T-Cell Prolymphocytic Leukemia (off-label) (must meet all):

1. Diagnosis of symptomatic T-cell prolymphocytic leukemia;
2. Prescribed by or in consultation with an oncologist or hematologist;
3. Age ≥ 18 years;
4. Prescribed as a component of FMC (fludarabine, mitoxantrone, and cyclophosphamide);
5. Dose is supported by practice guidelines or peer-reviewed literature for the relevant off-label use (prescriber must submit supporting evidence).Prescribed regimen must be FDA-approved or recommended by NCCN.
6. Total cumulative lifetime dose does not exceed 140 mg/m².
   Approval duration:
   Medicaid/HIM/ICHRA – 12 months
   Commercial – 6 months or to the member’s renewal date, whichever is longer

E. Acute Lymphoblastic Leukemia (off-label) (must meet all):

1. Diagnosis of acute lymphoblastic leukemia (ALL);
2. Prescribed by or in consultation with an oncologist or hematologist;
3. Disease is relapsed/refractory;
4. Member meets one of the following (a or b):
   a. Age ≥ 18 years, and both of the following (i and ii):
   i. Disease is one of the following (1, 2, or 3):
   1) Philadelphia chromosome (Ph)-negative B-ALL;
   2) Ph-positive B-ALL, and refractory to tyrosine kinase inhibitor therapy (e.g., dasatinib, imatinib, ponatinib, nilotinib, bosutinib);
   3) T-ALL;
   ii. Mitoxantrone is prescribed as a component of one of the following (1, 2, or 3):
   1) An alkylator combination regimen (e.g., etoposide, ifosfamide, and mitoxantrone);
   2) FLAM (fludarabine, cytarabine, and mitoxantrone);
   3) For T-ALL only: mitoxantrone, etoposide, and cytarabine;
   b. Age < 18 years, and disease is one of the following (i, ii, or iii):
   i. BCR::ABL1-negative B-ALL as a component of UKALL R3 or COG AALL 1331;
   ii. BCR::ABL1-positive B-ALL in combination with dasatinib or imatinib as a component of UKALL R3 or COG AALL 1331;
   iii. T-ALL as a component of UKALL R3 Block 1 (dexamethasone, mitoxantrone, pegaspargase, and vincristine);
5. Dose is supported by practice guidelines or peer-reviewed literature for the relevant off-label use (prescriber must submit supporting evidence).Prescribed regimen must be FDA-approved or recommended by NCCN.
6. Total cumulative lifetime dose does not exceed 140 mg/m².
   Approval duration:
   Medicaid/HIM/ICHRA – 12 months
   Commercial – 6 months or to the member’s renewal date, whichever is longer

F. Other diagnoses/indications (must meet 1 or 2):

1. If this drug has recently (within the last 6 months) undergone a label change (e.g., newly approved indication, age expansion, new dosing regimen) that is not yet reflected in this policy, refer to one of the following policies (a or b):
   a. For drugs on the formulary (commercial, health insurance marketplace/ICHRA) or PDL (Medicaid), the no coverage criteria policy for the relevant line of business: CP.CPA.190 for commercial, HIM.PA.33 for health insurance marketplace/ICHRA, and CP.PMN.255 for Medicaid; or
   b. For drugs NOT on the formulary (commercial, health insurance marketplace/ICHRA) or PDL (Medicaid), the non-formulary policy for the relevant line of business: CP.CPA.190 for commercial, HIM.PA.103 for health insurance marketplace/ICHRA, and CP.PMN.16 for Medicaid.
2. If the requested use (e.g., diagnosis, age, dosing regimen) is NOT specifically listed under section III (Diagnoses/Indications for which coverage is NOT authorized) AND criterion 1 above does not apply, refer to the off-label use policy for the relevant line of business: CP.CPA.09 for commercial, HIM.PA.154 for health insurance marketplace/ICHRA, and CP.PMN.53 for Medicaid.

II. Continued Therapy

A. Multiple Sclerosis (must meet all):

1. Member meets one of the following (a or b):
   a. Currently receiving medication via Centene benefit or member has previously met initial approval criteria;
   b. Member is currently receiving medication and is enrolled in a state and product with continuity of care regulations (refer to state specific addendums for CC.PHARM.03A and CC.PHARM.03B);
2. Member is responding positively to therapy;
3. Mitoxantrone is not prescribed concurrently with other disease modifying therapies for MS (see Appendix D);
4. If request is for a dose increase, new dose does not exceed the following (a and b):
   a. 12 mg/m² every 3 months;
   b. Total cumulative lifetime dose of 140 mg/m².
   Approval duration:
   Medicaid/HIM/ICHRA – 12 months
   Commercial – 6 months or to the member’s renewal date, whichever is longer

B. All Other Indications in Section I (must meet all):

1. Currently receiving medication via Centene benefit or documentation supports that member is currently receiving mitoxantrone for an oncology indication listed in Section I;
2. Member is responding positively to therapy;
3. If request is for a dose increase, request meets one of the following (a, b, or c):
   a. Prostate cancer: New dose does not exceed 14 mg/m² every 21 days;
   b. ANLL: New dose does not exceed 12 mg/m² per infusion;
   c. Any indication: New dose is supported by practice guidelines or peer-reviewed literature for the relevant off-label use (prescriber must submit supporting evidence);
   Prescribed regimen must be FDA-approved or recommended by NCCN.
4. Total cumulative lifetime dose does not exceed 140 mg/m².
   Approval duration:
   Medicaid/HIM/ICHRA – 12 months
   Commercial – 6 months or to the member’s renewal date, whichever is longer

C. Other diagnoses/indications (must meet 1 or 2):

1. If this drug has recently (within the last 6 months) undergone a label change (e.g., newly approved indication, age expansion, new dosing regimen) that is not yet reflected in this policy, refer to one of the following policies (a or b):
   a. For drugs on the formulary (commercial, health insurance marketplace/ICHRA) or PDL (Medicaid), the no coverage criteria policy for the relevant line of business: CP.CPA.190 for commercial, HIM.PA.33 for health insurance marketplace/ICHRA, and CP.PMN.255 for Medicaid; or
   b. For drugs NOT on the formulary (commercial, health insurance marketplace/ICHRA) or PDL (Medicaid), the non-formulary policy for the relevant line of business: CP.CPA.190 for commercial, HIM.PA.103 for health insurance marketplace/ICHRA, and CP.PMN.16 for Medicaid.
2. If the requested use (e.g., diagnosis, age, dosing regimen) is NOT specifically listed under section III (Diagnoses/Indications for which coverage is NOT authorized) AND criterion 1 above does not apply, refer to the off-label use policy for the relevant line of business: CP.CPA.09 for commercial, HIM.PA.154 for health insurance marketplace/ICHRA, and CP.PMN.53 for Medicaid.

III. Diagnoses/Indications for which coverage is NOT authorized:

A. Non-FDA approved indications, which are not addressed in this policy, unless there is sufficient documentation of efficacy and safety according to the off label use policy – CP.CPA.09 for commercial, HIM.PA.154 for health insurance marketplace/ICHRA, and CP.PMN.53 for Medicaid or evidence of coverage documents;

B. Primary progressive MS.

IV. Appendices/General Information

Appendix A: Abbreviation/Acronym Key

ALL: acute lymphoblastic leukemia
ANLL: acute nonlymphocytic leukemia
NCCN: National Comprehensive Cancer Network
FDA: Food and Drug Administration
Ph: Philadelphia chromosome
MS: multiple sclerosis

Appendix B: Therapeutic Alternatives

This table provides a listing of preferred alternative therapy recommended in the approval criteria. The drugs listed here may not be a formulary agent for all relevant lines of business and may require prior authorization.

Therapeutic alternatives are listed as Brand name® (generic) when the drug is available by brand name only and generic (Brand name®) when the drug is available by both brand and generic.

Appendix C: Contraindications/Boxed Warnings

• Contraindication(s): prior hypersensitivity to mitoxantrone
• Boxed warning(s): cardiotoxicity, secondary leukemia

Appendix D: General Information

• Disease-modifying therapies for MS are: glatiramer acetate (Copaxone®, Glatopa®), interferon beta-1a (Avonex®, Rebif®), interferon beta-1b (Betaseron®, Extavia®), peginterferon beta-1a (Plegridy®), dimethyl fumarate (Tecfidera®), diroximel fumarate (Vumerity®), monomethyl fumarate (Bafiertam®), fingolimod (Gilenya®, Tascento ODT™), teriflunomide (Aubagio®), alemtuzumab (Lemtrada®), mitoxantrone (Novantrone®), natalizumab (Tysabri®), and biosimilar Tyruko®), ocrelizumab (Ocrevus®), ocrelizumab/hyaluronidase-ocsq (Ocrevus Zunovo™), cladribine (Mavenclad®), siponimod (Mayzent®), ozanimod (Zeposia®), ponesimod (Ponvory™), ublituximab-xiiy (Briumvi®), and ofatumumab (Kesimpta®).
• Mitoxantrone has Drugdex IIa recommendations for use in anthracycline-resistant breast cancer, liver cancer, and ovarian cancer; however, these indications are not supported by the National Comprehensive Cancer Network (NCCN). Of note, use of mitoxantrone in invasive breast cancer is actually listed as a use no longer recommended by the NCCN.
• Per the NCCN, prostate cancer that stops responding to traditional androgen deprivation therapy (i.e., hormone therapy) is categorized as castration-recurrent (also known as castration-resistant).

V. Dosage and Administration

VI. Product Availability

Multidose vials: 20 mg/10 mL, 25 mg/12.5 mL, 30 mg/15 mL

Coding Implications

Codes referenced in this clinical policy are for informational purposes only. Inclusion or exclusion of any codes does not guarantee coverage. Providers should reference the most up-to-date sources of professional coding guidance prior to the submission of claims for reimbursement of covered services.

Reviews, Revisions, and Approvals

Important Reminder

This clinical policy has been developed by appropriately experienced and licensed health care professionals based on a review and consideration of currently available generally accepted standards of medical practice; peer-reviewed medical literature; government agency/program approval status; evidence-based guidelines and positions of leading national health professional organizations; views of physicians practicing in relevant clinical areas affected by this clinical policy; and other available clinical information. The Health Plan makes no representations and accepts no liability with respect to the content of any external information used or relied upon in developing this clinical policy. This clinical policy is consistent with standards of medical practice current at the time that this clinical policy was approved. “Health Plan” means a health plan that has adopted this clinical policy and that is operated or administered, in whole or in part, by Centene Management Company, LLC, or any of such health plan’s affiliates, as applicable.