CurrentCentenePolicy CP PHAR.258

Mitoxantrone clinical coverage policy

Defines medical necessity criteria, initial and continued approval, dosing limits, allowed indications (MS, hormone-refractory prostate cancer, ANLL, selected lymphomas, ALL), exclusions, approval durations, cumulative lifetime dose limits, provider documentation requirements, and coding implications for mitoxantrone across Centene lines of business (Commercial, HIM, Medicaid).

Policy Summary

PayerCentene

PolicyMitoxantrone clinical coverage policy

Policy CodePolicy CP PHAR.258

Change TypeAnnual reviews; multiple material revisions

Effective Date08.01.16

Next Review Date

Key ActionProvider must submit documentation (office chart notes, labs, or other clinical information) supporting that member has met all approval criteria.

POLICY UPDATE CHANGES

2Q 2025 annual review: for MS, removed requirements for documentation of baseline relapses/EDSS and specific measures of positive response; removed Extavia preferred notation; increased Medicaid/HIM continued approval duration from 6 to 12 months; added step therapy bypass for IL HIM per IL HB 5395.

2Q 2024 annual review: rearranged ALL criteria to clarify relapsed/refractory disease, added allowable regimen for adult T-ALL, specified regimens for pediatric Ph-positive B-ALL per NCCN; removed Hodgkin and follicular lymphoma as coverable diagnoses.

2Q 2022 annual review: removed references to brand Novantrone, removed mantle cell lymphoma as coverable, clarified coverable ALL types per NCCN, clarified interferon-beta redirections.

2Q 2021 annual review: lymphoma updated per NCCN to include Hodgkin lymphoma and T-cell prolymphocytic leukemia references updated.

Coverage Summary

Coverage stance: covered_with_criteria. Scope summary: Defines medical necessity criteria, initial and continued approval, dosing limits, allowed indications (MS, hormone-refractory prostate cancer, ANLL, selected lymphomas, relapsed/refractory ALL), exclusions, approval durations, cumulative lifetime dose limits, provider documentation requirements, and coding implications for mitoxantrone across Centene lines of business (Commercial, HIM, Medicaid).

Listed covered indications: FDA-approved for reduction of neurologic disability and/or relapse frequency in certain forms of multiple sclerosis (secondary progressive, progressive relapsing, or worsening relapsing-remitting MS); treatment of pain related to advanced hormone-refractory (castration-resistant) prostate cancer in combination with corticosteroids; and initial therapy of acute nonlymphocytic leukemia (ANLL) in adults in combination with other agents. Off-label/selected covered uses per policy include certain lymphomas and relapsed/refractory acute lymphoblastic leukemia (ALL) when criteria are met.

Key dosing and cumulative limits noted in scope: single-dose limits such as 12 mg/m2 every 3 months for MS, ≤ 12 mg/m2 per infusion for ANLL, ≤ 14 mg/m2 every 21 days for prostate cancer, and a total cumulative lifetime dose limit of ≤ 140 mg/m2.

Background safety/contraindications: Mitoxantrone carries boxed warnings for cardiotoxicity and secondary leukemia, and is contraindicated in patients with a history of prior hypersensitivity to mitoxantrone.

Dose and Cumulative Limits

Mitoxantrone single dose for MS12 mg/m2 every 3 months

Mitoxantrone single dose for ANLL≤ 12 mg/m2 per infusion

Mitoxantrone single dose for prostate cancer≤ 14 mg/m2 every 21 days

Total cumulative lifetime dose≤ 140 mg/m2

Initial Therapy Criteria

Initial Approval Criteria - Multiple Sclerosis

Mitoxantrone is medically necessary for MS when ALL of the following are met:

ALL of the following

Diagnosis: Multiple sclerosis (relapsing-remitting MS or secondary progressive MS)
Primary progressive MS is excluded
For relapsing-remitting MS: failure of all of the following unless contraindicated or intolerant
- Dimethyl fumarate (Tecfidera) tried at up to maximally indicated doses
- Teriflunomide (Aubagio) tried at up to maximally indicated doses

Continuation Therapy Criteria

Continued Therapy - Multiple Sclerosis

For continued therapy in MS, ALL of the following must be met:

ALL of the following

Member status (one of)
- Member is currently receiving medication via Centene benefit
- Member has previously met initial approval criteria
- Member is currently receiving medication and is enrolled in a state/product with continuity of care regulations
Member is responding positively to therapy
Documentation of positive response requirements removed per 2Q2025

Provider Actions

Prior Authorization

Prior authorization required

Prior authorization may be required for mitoxantrone and for disease-modifying therapies for MS; prescriber must submit supporting evidence for off-label uses.

Documentation Required

Submit supporting documentation

Provider must submit documentation (such as office chart notes, lab results, or other clinical information) supporting that the member has met all approval criteria. Acceptable documentation types include office chart notes, laboratory results, and other clinical information or supporting evidence for off‑label uses (e.g., practice guidelines or peer‑reviewed literature).

Applicable Codes

HCPCS J-code for mitoxantroneHCPCS

J9293

Mitoxantrone HCl, 1 mg (HCPCS code listed in policy)

Clinical Evidence & References

Evidence sources cited in the policy include the mitoxantrone prescribing information: Mitoxantrone Prescribing Information, April 2021; accessed Jan 23, 2025.

Guideline references include the NCCN Drugs & Biologics Compendium and the American Academy of Neurology practice guideline on disease-modifying therapies (AAN; reaffirmed Oct 19, 2024).

The prescribing information contains the boxed warnings for cardiotoxicity and secondary leukemia; these boxed warnings and the contraindication for prior hypersensitivity to mitoxantrone are listed in the policy's Appendix B (Boxed warning(s): cardiotoxicity, secondary leukemia; Contraindication(s): prior hypersensitivity to mitoxantrone).

Definitions & Background

Mitoxantrone is a synthetic antineoplastic anthracenedione with FDA approvals that include: reducing neurologic disability and/or the frequency of clinical relapses in specified forms of multiple sclerosis (secondary progressive, progressive relapsing, or worsening relapsing-remitting MS); treatment of pain related to advanced hormone-refractory (castration-resistant) prostate cancer in combination with corticosteroids; and initial therapy of acute nonlymphocytic leukemia (ANLL) in adults in combination with other approved drugs.

Dosage and administration details from the product labeling and policy include: for relapsing MS, 12 mg/m2 IV given approximately every 3 months (with a cumulative lifetime dose threshold of > 140 mg/m2 noted as a limit); for hormone-refractory prostate cancer, 12–14 mg/m2 IV every 21 days; and for ANLL, induction regimens using 12 mg/m2 IV on specified days. The policy enforces a total cumulative lifetime dose limit of ≤ 140 mg/m2 across indications.

Appendix B of the policy lists safety information: boxed warnings include cardiotoxicity and secondary leukemia, and the drug is contraindicated in patients with prior hypersensitivity to mitoxantrone.

Definitions provided in the policy: ANLL = acute nonlymphocytic leukemia (including AML, promyelocytic, monocytic, and erythroid acute leukemias); ALL = acute lymphoblastic leukemia; MS = multiple sclerosis; NCCN = National Comprehensive Cancer Network.

Revision History

05.25.2025revisedLatest

05.24.2024revised

05.22.2022

Policy Summary

PayerCentene

PolicyMitoxantrone clinical coverage policy

Policy CodePolicy CP PHAR.258

Change TypeAnnual reviews; multiple material revisions

Effective Date08.01.16

Next Review Date

Key ActionProvider must submit documentation (office chart notes, labs, or other clinical information) supporting that member has met all approval criteria.

On This Page

Initial Approval Criteria - Hormone-refractory (castration-resistant) Prostate Cancer

Mitoxantrone is medically necessary for advanced/metastatic prostate cancer when ALL of the following are met:

ALL of the following

Diagnosis: advanced or metastatic prostate cancer
Disease is hormone-refractory (castration-resistant)
Prescribed by or in consultation with an oncologist
Age: ≥ 18 years
Mitoxantrone is prescribed concurrently with a corticosteroid (e.g., prednisone)
Dose requirement (one of)
- Dose does not exceed 14 mg/m2 every 21 days≤ 14 mg/m2 every 21 days
- 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
Total cumulative lifetime dose does not exceed 140 mg/m2≤ 140 mg/m2

Initial Approval Criteria - Acute Nonlymphocytic Leukemia (ANLL)

Mitoxantrone is medically necessary for ANLL when ALL of the following are met:

ALL of the following

Diagnosis: acute nonlymphocytic leukemia (including acute myelogenous leukemia, promyelocytic, monocytic, erythroid acute leukemias)
Prescribed by or in consultation with an oncologist or hematologist
Age: ≥ 18 years
Therapy context (one of)
- Mitoxantrone is prescribed in combination with other therapies for the diagnosis
- Dose is supported by practice guidelines or peer-reviewed literature for the relevant off-label use (prescriber must submit supporting evidence)
Dose limit for infusion: does not exceed 12 mg/m2 per infusion≤ 12 mg/m2 per infusion
Prescribed regimen must be FDA-approved or recommended by NCCN
Total cumulative lifetime dose does not exceed 140 mg/m2≤ 140 mg/m2

Initial Approval Criteria - Lymphoma (off-label)

Mitoxantrone is medically necessary for selected lymphomas when ALL of the following are met:

ALL of the following

Diagnosis (one of the following B-cell lymphomas) or specific T-cell disease
- Diffuse large B-cell lymphoma
- High B-cell lymphoma
- HIV-related B-cell lymphoma
- Post-transplant lymphoproliferative disorder
- Symptomatic T-cell prolymphocytic leukemia as component of FMC (fludarabine, mitoxantrone, cyclophosphamide)
Prescribed as second line or subsequent therapy when applicable
Prescribed by or in consultation with an oncologist or hematologist
Age: > 18 years
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
Total cumulative lifetime dose does not exceed 140 mg/m2≤ 140 mg/m2

Initial Approval Criteria - Acute Lymphoblastic Leukemia (ALL) (off-label)

Mitoxantrone is medically necessary for relapsed/refractory ALL when ALL of the following are met:

ALL of the following

Diagnosis: acute lymphoblastic leukemia (ALL)
Disease status: relapsed or refractory
Prescribed by or in consultation with an oncologist or hematologist
Age and regimen requirements (one of)
- For adults (≥ 18 years)
  - Age ≥ 18 years
  - Mitoxantrone is prescribed as a component of an allowable regimen (e.g., alkylator combination such as etoposide, ifosfamide, mitoxantrone; FLAM; mitoxantrone/etoposide/cytarabine for T-ALL)
- For pediatric considerations
  - Age criteria per regimen (documented by prescriber)
  - Allowable regimens include pediatric-specified regimens such as UKALL R3 or COG AALL 1331 combinations where indicated (e.g., BCR:ABL-positive B-ALL in combination with dasatinib or imatinib as component of UKALL R3 or COG AALL 1331)
Prescribed regimen must be FDA-approved or recommended by NCCN
Dose is supported by practice guidelines or peer-reviewed literature for the relevant off-label use (prescriber must submit supporting evidence)
Total cumulative lifetime dose does not exceed 140 mg/m2≤ 140 mg/m2

Initial Approval Criteria - Other diagnoses/indications

For other uses, one of the following must be met:

ANY of the following

If drug is on formulary or PDL: follow the no coverage criteria policy for the relevant line of business (CP.CPA.190 for commercial, HIM.PA.33 for marketplace, CP.PMN.255 for Medicaid)
If drug is NOT on formulary/PDL: follow the non-formulary policy for the relevant line of business (CP.CPA.190 commercial, HIM.PA.103 marketplace, CP.PMN.16 Medicaid)
If requested use is not listed in Section I and criterion above does not apply: refer to off-label use policy for relevant line of business (CP.CPA.09 commercial, HIM.PA.154 marketplace, CP.PMN.53 Medicaid)

Continued Therapy - Other Indications (oncology)

For continued therapy for oncology indications listed in Section I, ALL must be met:

ALL of the following

Member is currently receiving medication via Centene benefit or documentation supports current use for an oncology indication listed in Section I
Member is responding positively to therapy
If dose increase requested, new dose must meet one of
- ANLL: new dose does not exceed 12 mg/m2 per infusion≤ 12 mg/m2 per infusion
- Prostate cancer: new dose does not exceed 14 mg/m2 every 21 days≤ 14 mg/m2 every 21 days
- Off-label: new dose is supported by practice guidelines or peer-reviewed literature (prescriber must submit supporting evidence)
Prescribed regimen must be FDA-approved or recommended by NCCN
Total cumulative lifetime dose does not exceed 140 mg/m2≤ 140 mg/m2

Billing Rule

Dose and cumulative limits must be observed

Claims should reflect dosing that does not exceed the policy's per‑dose and cumulative lifetime limits. The HCPCS code referenced for mitoxantrone is J9293. Observe the policy thresholds: MS dose 12 mg/m2 every 3 months; ANLL dose ≤ 12 mg/m2 per infusion; prostate cancer dose ≤ 14 mg/m2 every 21 days; total cumulative lifetime dose ≤ 140 mg/m2.

Documentation Required

Specialist prescriber requirement

Mitoxantrone must be prescribed by or in consultation with an appropriate specialist: for multiple sclerosis, prescribed by or in consultation with a neurologist; for oncology indications (including prostate cancer, ANLL, lymphoma, ALL), prescribed by or in consultation with an oncologist or hematologist.