Centene Mitoxantrone Coverage & Prior Auth Update

Coverage Criteria

Initial Therapy

Covered when ALL of the following are met for each indication group

I.A Multiple Sclerosis (Initial): 1. Diagnosis of relapsing-remitting MS with failure of dimethyl fumarate, teriflunomide, fingolimod, and an interferon-beta agent or glatiramer at up to maximally indicated doses unless contraindicated or intolerant, OR diagnosis of secondary progressive MS; 2. Prescribed by or in consultation with a neurologist; 3. Age >= 18 years; 4. Mitoxantrone is not prescribed concurrently with other disease modifying therapies for MS; 5. Dose does not exceed 12 mg/m2 every 3 months; 6. Total cumulative lifetime dose does not exceed 140 mg/m2.

I.B Prostate Cancer (Initial): 1. Diagnosis of advanced or metastatic prostate cancer; 2. Prescribed by or in consultation with an oncologist; 3. Age >= 18 years; 4. Disease is hormone-refractory (castration-resistant); 5. Mitoxantrone is prescribed concurrently with a corticosteroid (e.g., prednisone); 6. Request meets one of the following: a) dose does not exceed 14 mg/m2 every 21 days, or b) dose is supported by practice guidelines or peer-reviewed literature (prescriber must submit supporting evidence); 7. Total cumulative lifetime dose does not exceed 140 mg/m2.

I.C Acute Nonlymphocytic Leukemia (ANLL) (Initial): 1. Diagnosis of ANLL (including myelogenous/acute myelogenous, 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) dose does not exceed 12 mg/m2 per infusion, or b) dose is supported by practice guidelines or peer-reviewed literature (prescriber must submit supporting evidence); 6. Total cumulative lifetime dose does not exceed 140 mg/m2.

I.D T-Cell Prolymphocytic Leukemia (off-label) (Initial): 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, cyclophosphamide); 5. Dose is supported by practice guidelines or peer-reviewed literature for the off-label use (prescriber must submit supporting evidence); 6. Total cumulative lifetime dose does not exceed 140 mg/m2.

I.E Acute Lymphoblastic Leukemia (ALL) (off-label) (Initial): 1. Diagnosis of 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) Age >= 18 years and i) disease is Ph-negative B-ALL, Ph-positive B-ALL refractory to TKI therapy, or T-ALL, AND ii) mitoxantrone is prescribed as a component of an alkylator combination (e.g., etoposide, ifosfamide, mitoxantrone), FLAM (fludarabine, cytarabine, mitoxantrone), or for T-ALL the mitoxantrone/etoposide/cytarabine regimen; b) Age < 18 years and disease is 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, or iii) T-ALL as a component of UKALL R3 Block 1; 5. Dose is supported by practice guidelines or peer-reviewed literature for the off-label use (prescriber must submit supporting evidence); 6. Total cumulative lifetime dose does not exceed 140 mg/m2.

Continuation Therapy

Covered for continuation when ALL of the following are met

II.A Continued Therapy — Multiple Sclerosis: 1. Member is currently receiving mitoxantrone via the Centene benefit or has previously met initial approval criteria, OR continuity of care provisions apply; 2. Member is responding positively to therapy; 3. Mitoxantrone is not prescribed concurrently with other disease modifying therapies for MS; 4. If request is for a dose increase, new dose does not exceed 12 mg/m2 every 3 months and total cumulative lifetime dose does not exceed 140 mg/m2.

II.B Continued Therapy — Other Indications: 1. Member is currently receiving mitoxantrone via the Centene benefit or documentation supports current use for an oncology indication listed in Section I; 2. Member is responding positively to therapy; 3. If request is for a dose increase, the new dose must meet one of the following: 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 (prescriber must submit supporting evidence); 4. Total cumulative lifetime dose does not exceed 140 mg/m2.

Covered Indications with dosing and limits

Coverage includes specific indications with dosing and cumulative dose limits; certain diagnoses are explicitly not authorized.

Relapsing MS: Covered for relapsing multiple sclerosis with dosing of 12 mg/m2 IV given as a short (approximately 5–15 minute) infusion every 3 months; cumulative lifetime dose limit applies.cumulative lifetime dose < 140 mg/m2

See Appendix D for disease-modifying therapy context and alternatives.

Hormone-refractory prostate cancer: Covered dosing 12–14 mg/m2 IV every 21 days; cumulative lifetime dose limit applies.cumulative lifetime dose < 140 mg/m2

NCCN categorizes castration-recurrent (castration-resistant) prostate cancer and referenced guidance applies.

ANLL (acute nonlymphocytic leukemia): Induction: 12 mg/m2 IV daily on Days 1–3 with possible second induction (2 days) if incomplete antileukemic response; Consolidation: 12 mg/m2 IV on Days 1–2; cumulative lifetime dose limit applies.

Mitoxantrone is not indicated for the treatment of patients with primary progressive multiple sclerosis. This statement aligns with the drug's FDA-approved limitations of use and must be applied when evaluating medical necessity for MS indications.

Primary progressive multiple sclerosis is explicitly listed among diagnoses for which coverage is NOT authorized under this policy. Requests for mitoxantrone to treat primary progressive MS should be denied unless an alternative covered indication is documented.

Requests for non‑FDA approved indications that are not specifically addressed in this policy are not authorized unless the provider supplies sufficient documentation of efficacy and safety in accordance with the applicable off‑label use policy (CP.CPA.09 for Commercial, HIM.PA.154 for HIM/ICHRA, CP.PMN.53 for Medicaid) or relevant evidence of coverage documents.

Coding and Dose Limits

HCPCS CodesHCPCS

J9293

Injection, mitoxantrone HCl, per 5 mg

inv-08: Total cumulative lifetime dose — 140 mg/m2

Total cumulative lifetime dose140 mg/m2

Applied across indicationsLimit applies to MS, prostate cancer, and ANLL per dosing sections

Dose comparison notePolicy specifies dose limits per infusion/regimen and enforces cumulative lifetime total

inv-09: Cumulative lifetime dose — >= 140 mg/m2

Cumulative lifetime dose threshold>= 140 mg/m2

Indications referencing thresholdRelapsing MS, hormone‑refractory prostate cancer, and ANLL specify this cumulative maximum

Provider Actions & Requirements

Prior Authorization

Prior Authorization Required

Prior authorization is required. Provider must demonstrate the member meets the diagnosis and prior treatment criteria (including required MS step-therapy failures where applicable) and submit supporting clinical documentation.

Prior authorization required for disease-modifying therapies for MS
Provider must document diagnosis and prior treatment failures per policy criteria

Prior Authorization

Prior Authorization Duration & Recent Updates

Approval durations vary by line of business. Medicaid, HIM, and ICHRA approvals are authorized for 12 months. Commercial approvals are authorized for 6 months or to the member's renewal date, whichever is longer. Recent policy updates (2Q 2025–2Q 2026) increased Medicaid/HIM continued approval duration for chronic conditions and added ICHRA.

Covered Regimens and Schedules

Regimen	Indication	Coverage status	Notes / Dosing
FMC (fludarabine, mitoxantrone, cyclophosphamide)	T‑cell prolymphocytic leukemia (off‑label)		Prescribed as a component of FMC; prescriber must submit supporting evidence that dose is supported by practice guidelines or peer‑reviewed literature. Total cumulative lifetime dose must not exceed 140 mg/m2.

Example regimen	Indication	Notes / Details
Alkylator combination (e.g., etoposide, ifosfamide, mitoxantrone)	Relapsed/refractory acute lymphoblastic leukemia (ALL)	Mitoxantrone prescribed as component of alkylator combination per regimen examples; dose must be supported by guidelines or literature and prescriber must submit evidence. Total cumulative lifetime dose ≤ 140 mg/m2.
FLAM (fludarabine, cytarabine, mitoxantrone)	Relapsed/refractory ALL	Mitoxantrone as component of FLAM; prescriber must submit supporting evidence that dose is guideline‑supported. Total cumulative lifetime dose ≤ 140 mg/m2.
T‑ALL regimen: mitoxantrone, etoposide, cytarabine	T‑cell ALL (relapsed/refractory)	Mitoxantrone included in T‑ALL regimen examples; dose must be supported by practice guidelines or peer‑reviewed literature with submitted evidence. Pediatric inclusion requires specified protocols (see UKALL R3 or COG AALL 1331 for pediatric B‑ALL/T‑ALL components).
UKALL R3 or COG AALL 1331 (pediatric protocols)	Pediatric B‑ALL / T‑ALL (as specified)	For age <18 years, mitoxantrone use must be as a component of UKALL R3 or COG AALL 1331 where indicated (e.g., BCR::ABL1‑negative B‑ALL or specified blocks). Prescriber must submit evidence. Total cumulative lifetime dose ≤ 140 mg/m2.

Indication	Dosing	Infusion	Coverage status / Limits
Relapsing multiple sclerosis	12 mg/m2 IV every 3 months	Short intravenous infusion (~5–15 minutes)	Covered with criteria; cumulative lifetime dose limit applies (maximum cumulative lifetime dose ≥ 140 mg/m2).

Indication	Dosing	Schedule	Coverage status / Limits
Hormone‑refractory (castration‑resistant) prostate cancer	12–14 mg/m2 IV	Every 21 days	Covered with criteria when prescribed with a corticosteroid; cumulative lifetime dose limit applies (maximum cumulative lifetime dose ≥ 140 mg/m2).

Indication	Phase / Setting	Dosing	Coverage status / Notes
Acute nonlymphocytic leukemia (ANLL)	Induction	12 mg/m2 daily on Days 1–3 (IV infusion); a second induction course of 2 days may be given if antileukemic response is incomplete.	Covered with criteria; cumulative lifetime dose limit applies (maximum cumulative lifetime dose ≥ 140 mg/m2).
Acute nonlymphocytic leukemia (ANLL)	Consolidation	12 mg/m2 daily on Days 1–2 (IV infusion)	Covered with criteria; total cumulative lifetime dose must not exceed 140 mg/m2.

Line of Therapy Definitions

initial

Used as initial chemotherapy in combination with corticosteroids for pain related to advanced hormone-refractory (castration-resistant) prostate cancer; must be prescribed with a corticosteroid and by or in consultation with an oncologist.

initial

Initial therapy of acute nonlymphocytic leukemia (ANLL) in adults in combination with other approved drugs; must be prescribed by or in consultation with an oncologist or hematologist.

salvage

Pediatric B-ALL (salvage): For pediatric BCR::ABL1-negative B-ALL, mitoxantrone use must be as a component of UKALL R3 or COG AALL 1331 per NCCN; BCR::ABL1-positive pediatric B-ALL must be in combination with dasatinib or imatinib as a component of those protocols.

Requirement added in 2Q2026 update per NCCN; prescriber must submit regimen documentation.

Biomarker / Testing Requirements

inv-24: BCR::ABL1 — biomarker reference (empty summary in inventory)

BiomarkerBCR::ABL1

Use caseReferenced in pediatric B-ALL revisions (Ph renamed to BCR::ABL1) for specifying Ph‑positive/negative status

Policy contextRequired for pediatric B-ALL line/regimen specifications per 2Q updates

Background

Mitoxantrone is a synthetic antineoplastic anthracenedione with FDA indications for certain multiple sclerosis subtypes (reducing neurologic disability and/or relapse frequency in secondary progressive, progressive relapsing, or worsening relapsing‑remitting MS), for pain related to advanced hormone‑refractory prostate cancer when given as initial chemotherapy with corticosteroids, and for initial therapy of acute nonlymphocytic leukemia in adults as part of combination regimens. The FDA labeling also includes the specific limitation that mitoxantrone is not indicated for primary progressive MS.

Definitions

inv-19: Mitoxantrone — short definition and FDA indication note

DefinitionMitoxantrone is a synthetic antineoplastic anthracenedione.

FDA indications (selected)Indicated for certain forms of MS (secondary progressive, progressive relapsing, or worsening relapsing-remitting), pain related to advanced hormone‑refractory prostate cancer (with corticosteroids), and initial therapy of acute nonlymphocytic leukemia in adults in combination with other drugs.

LimitationNot indicated for primary progressive multiple sclerosis.

inv-20: Cumulative lifetime dose — the summed total mitoxantrone dose over a patient's life; policy specifies 60 140 mg/m2 as maximum.

DefinitionCumulative lifetime dose = the summed total mitoxantrone dose received over a patient's life.

Policy maximum

Revision History

05.26.2026material_changeLatest

2Q2026 annual review: for pediatric BCR::ABL1-negative B-ALL, added requirement that mitoxantrone be used as a component of UKALL R3 or COG AALL 1331 per NCCN; removed B-cell lymphomas as coverable diagnoses; extended initial and continued approval duration for Medicaid and HIM from 6 to 12 months for maintenance chronic indications; added ICHRA line of business.

05.25.2025material_change

2Q2025 annual review: for MS removed baseline relapse/EDSS documentation requirements and specific response measures, removed notation of preferred interferon beta-1b product for Medicaid, increased Medicaid/HIM continued approval duration from 6 to 12 months for chronic MS, and added step therapy bypass for Illinois HIM per IL HB 5395; references reviewed and updated.

OpenPayer

Clinical Policy: Mitoxantrone