Centene ivosidenib (Tibsovo) Coverage Update

Coverage Criteria

Initial Therapy — AML

Covered when ALL of the following are met

AML initial approval: 1. Diagnosis of acute myeloid leukemia (AML); 2. Prescribed by or in consultation with an oncologist or hematologist; 3. Age ≥ 18 years; 4. Member meets one of the following (a or b): (a) Tibsovo is prescribed for induction, post-induction, or consolidation therapy and both of the following (i and ii): (i) Tibsovo is prescribed in combination with azacitidine or as monotherapy; (ii) one of the following: (1) age ≥ 75 years and disease is newly diagnosed; or (2) member is not a suitable candidate for or declines intensive induction chemotherapy; OR (b) disease is relapsed or refractory and Tibsovo is prescribed as a single agent; 5. Presence of an IDH1 mutation; 6. Member must use generic ivosidenib if available unless contraindicated or intolerant; 7. Request meets one of the following: (a) dose does not exceed 500 mg (2 tablets) per day; OR (b) dose is supported by practice guidelines or peer-reviewed literature for the relevant use (prescriber must submit supporting evidence).

Prescribed regimen must be FDA‑approved or recommended by NCCN.

Initial Therapy — Cholangiocarcinoma

Covered when ALL of the following are met

Cholangiocarcinoma initial approval: 1. Diagnosis of locally advanced or metastatic cholangiocarcinoma; 2. Prescribed by or in consultation with an oncologist; 3. Age ≥ 18 years; 4. Disease positive for an IDH1 mutation; 5. Prescribed as a single agent for disease progression on or after systemic treatment; 6. Member must use generic ivosidenib if available unless contraindicated or intolerant; 7. Request meets one of the following: (a) dose does not exceed 500 mg (2 tablets) per day; OR (b) dose is supported by practice guidelines or peer‑reviewed literature for the relevant use (prescriber must submit supporting evidence).

Prescribed regimen must be FDA‑approved or recommended by NCCN.

Initial Therapy — MDS

Covered when ALL of the following are met

MDS initial approval: 1. Diagnosis of myelodysplastic syndromes (MDS); 2. Prescribed by or in consultation with an oncologist or hematologist; 3. Age ≥ 18 years; 4. One of the following: (a) disease is relapsed or refractory; (b) disease progression, no response, or intolerance to prior systemic treatment; (c) disease is higher‑risk per IPSS‑R (intermediate, high, or very high); 5. Presence of an IDH1 mutation; 6. Member must use generic ivosidenib if available unless contraindicated or intolerant; 7. Request meets one of the following: (a) dose does not exceed 500 mg (2 tablets) per day; OR (b) dose is supported by practice guidelines or peer‑reviewed literature for the relevant use (prescriber must submit supporting evidence).

Prescribed regimen must be FDA‑approved or recommended by NCCN.

Initial Therapy — Chondrosarcoma (Off-label)

Covered when ALL of the following are met

Chondrosarcoma initial approval: 1. Diagnosis of conventional (grade 1–3) or dedifferentiated chondrosarcoma; 2. Prescribed by or in consultation with an oncologist; 3. Age ≥ 18 years; 4. Disease positive for an IDH1 mutation; 5. Member must use generic ivosidenib if available unless contraindicated or intolerant; 6. Request meets one of the following: (a) dose does not exceed 500 mg (2 tablets) per day; OR (b) dose is supported by practice guidelines or peer‑reviewed literature for the relevant off‑label use (prescriber must submit supporting evidence).

Off‑label; regimen must be FDA‑approved or recommended by NCCN.

Initial Therapy — Glioma (Off-label)

Covered when ALL of the following are met

Glioma initial approval: 1. Diagnosis of oligodendroglioma or astrocytoma; 2. Prescribed by or in consultation with an oncologist; 3. Age ≥ 18 years; 4. Disease positive for an IDH1 mutation; 5. Prescribed as a single agent; 6. Member is unable to tolerate Voranigo; 7. Member must use generic ivosidenib if available unless contraindicated or intolerant; 8. Request meets one of the following: (a) dose does not exceed 500 mg (2 tablets) per day; OR (b) dose is supported by practice guidelines or peer‑reviewed literature for the relevant off‑label use (prescriber must submit supporting evidence).

Off‑label; regimen must be FDA‑approved or recommended by NCCN.

Continuation Therapy

Covered when ALL of the following are met

Continuation therapy: 1. Member is currently receiving medication via Centene benefit, or documentation supports member has been receiving Tibsovo for at least 30 days; 2. Member is responding positively to therapy; 3. Member must use generic ivosidenib if available unless contraindicated or intolerant; 4. If request is for a dose increase, request meets one of the following: (a) new dose does not exceed 500 mg (2 tablets) per day; OR (b) new dose is supported by practice guidelines or peer‑reviewed literature for the relevant use (prescriber must submit supporting evidence).

Prescribed regimen must be FDA‑approved or recommended by NCCN. For AML or MDS without progression, continue for a minimum of 6 months to allow time for clinical response.

General Coverage

Coverage is provided for FDA‑approved indications and selected NCCN‑supported off‑label diagnoses when documentation meets policy and applicable off‑label use policies.

General coverage requirements: 1. Medication must be used for an FDA‑approved indication or a NCCN‑supported off‑label diagnosis with appropriate documentation per off‑label use policies (CP.CPA.09, HIM.PA.154, CP.PMN.53) or evidence of coverage documents; 2. Dosing per prescribing information (standard 500 mg PO once daily) unless higher dose is supported by guidelines/literature; 3. Prior authorization obtained and required clinical documentation submitted (diagnosis, IDH1 mutation status, prescriber specialty, prior therapies, and justification when applicable); 4. Member must use generic ivosidenib if available unless contraindicated or intolerant.

See appendices and referenced off‑label policies for specifics; boxed warning for differentiation syndrome applies to AML and MDS.

Non–FDA approved indications that are not specifically addressed in this policy are not authorized for coverage unless the provider submits sufficient documentation of efficacy and safety in accordance with the applicable off‑label use policy (see CP.CPA.09 for Commercial, HIM.PA.154 for Health Insurance Marketplace, and CP.PMN.53 for Medicaid) or other evidence of coverage documents.

Requests for ivosidenib for diagnoses that are not FDA‑approved require documentation demonstrating efficacy and safety consistent with the referenced off‑label use policies before coverage will be considered (CP.CPA.09, HIM.PA.154, CP.PMN.53).

Use of ivosidenib for non‑FDA approved indications without adequate off‑label supporting documentation may be considered not medically necessary and may be denied per the applicable off‑label use policy or evidence of coverage determinations.

Line of Therapy

first-line | second-line | salvage

Line of therapy notes: AML: may be used as newly diagnosed induction/post‑induction/consolidation in older/comorbid patients in combination with azacitidine or as monotherapy; AML and MDS: may be used for relapsed or refractory disease; Cholangiocarcinoma: used after progression on or after prior systemic therapy; Glioma/Chondrosarcoma: off‑label single‑agent uses as specified in criteria.

first-line | second-line

Updated line of therapy notes: Policy revisions: include combination with azacitidine or monotherapy for AML per FDA; post‑update pathways require monotherapy use in relapsed/refractory AML when specified and other line‑of‑therapy adjustments per NCCN and FDA updates.

Biomarker Requirements

inv-28: IDH1 mutation — biomarker requirement for covered indications

Biomarker requiredPresence of a susceptible IDH1 mutation is required for coverage across indicated tumor types (AML, cholangiocarcinoma, MDS, chondrosarcoma, glioma).

Test typeMutation must be detected by an FDA‑approved test when applicable per FDA labeling.

Applies toRequired for initial and continuation approvals in AML, cholangiocarcinoma, MDS, and off‑label chondrosarcoma and glioma per criteria.

inv-29: IDH1 — definition/key term

TermIDH1 = isocitrate dehydrogenase‑1.

RelevanceTarget of ivosidenib; presence of an IDH1 mutation is required for covered indications.

Covered Regimens and Dosing

Regimen	Details / indication-specific notes
Ivosidenib up to 500 mg/day (2 tablets)
Standard dosing: 500 mg PO once daily (tablet strength 250 mg). Use as monotherapy or in combination with azacitidine for specified AML populations per criteria. Maximum routine daily dose 500 mg/day; dose above 500 mg/day requires supporting evidence from practice guidelines or peer‑reviewed literature.

Regimen	Details / clinical use notes
Ivosidenib 500 mg PO once daily until disease progression or unacceptable toxicity
For AML: may be used as monotherapy or in combination with azacitidine per FDA label and policy criteria. Continue for a minimum of 6 months in AML or MDS unless progression or unacceptable toxicity to allow time for clinical response. Examples of alternative induction/systemic regimens are listed in Appendix B (e.g., cytarabine with idarubicin or daunorubicin; gemcitabine+cisplatin ± immunotherapy; FOLFOX; azacitidine, decitabine ± cedazuridine).

Regimen

Details / clinical use notes

Ivosidenib 500 mg PO once daily until disease progression or unacceptable toxicity

For AML: may be used as monotherapy or in combination with azacitidine per FDA label and policy criteria. Continue for a minimum of 6 months in AML or MDS unless progression or unacceptable toxicity to allow time for clinical response. Examples of alternative induction/systemic regimens are listed in Appendix B (e.g., cytarabine with idarubicin or daunorubicin; gemcitabine+cisplatin ± immunotherapy; FOLFOX; azacitidine, decitabine ± cedazuridine).

Coding

No explicit CPT/HCPCS/NDC codes in this sectionmixed

No codes listed

inv-12: Minimum treatment duration to assess response — Continue for a minimum of 6 months in AML or MDS unless progression or unacceptable toxicity

Minimum durationContinue for a minimum of 6 months in AML or MDS unless there is disease progression or unacceptable toxicity.

PurposeAllows time to assess clinical response in patients without progression or unacceptable toxicity.

Applies toPatients with AML or MDS receiving ivosidenib where disease has not progressed and toxicity is acceptable.

Provider Actions and Prior Authorization

Prior Authorization

Prior Authorization Required

Prior authorization is required. Provider must submit documentation (such as office chart notes, pathology or molecular testing results, lab reports, or other clinical information) supporting the diagnosis and that the member meets all approval criteria. Requests should include documentation of IDH1 mutation status, prescriber specialty (oncologist or hematologist where specified), member age (≥ 18 years), and dosing information (dose does not exceed 500 mg/day unless supported by guideline or peer-reviewed literature).

Prior authorization required with documentation of diagnosis and IDH1 mutation status
Prescriber specialty (oncologist or hematologist) must be documented where indicated
Age ≥ 18 years must be documented
Dose ≤ 500 mg/day unless alternative dosing is supported by guidelines or literature

Documentation Required

Required Clinical Documentation

Definitions and Safety Information

Ivosidenib (Tibsovo) is an inhibitor of isocitrate dehydrogenase‑1 (IDH1) and is indicated for treatment of IDH1‑mutant malignancies covered under this policy, including specified populations of acute myeloid leukemia (AML), relapsed or refractory myelodysplastic syndromes (MDS), and previously treated locally advanced or metastatic cholangiocarcinoma. The medication is administered orally, typically at a regimen of 500 mg once daily (two 250 mg tablets) until disease progression or unacceptable toxicity, and carries a boxed warning for differentiation syndrome which applies to AML and MDS. Coverage is biomarker‑driven and requires documentation of an IDH1 mutation for eligible indications.

inv-22: IDH1 — key term definition

DefinitionIDH1: isocitrate dehydrogenase‑1 (enzyme).

Clinical roleMutation in IDH1 identifies patients eligible for ivosidenib per policy criteria and FDA indications.

SourceDefined in policy description and Appendix A (Abbreviation/Acronym Key).

inv-23: IPSS-R — key term definition

Revision History

2025-07-07annual_reviewLatest

4Q 2025 annual review: revised Medicaid and HIM initial approval durations to 12 months; for AML removed age ≥60 pathway and newly diagnosed requirement, required monotherapy in relapsed/refractory AML, and allowed 'unsuitable candidate or decline' instead of inability-to-use-intensive-chemotherapy; for MDS added option for higher-risk disease; for glioma added requirement for lack of Voranigo tolerability; references reviewed and updated.

2023-11-27policy_revision

RT4: added newly approved MDS indication; added therapeutic alternative examples in Appendix B for MDS; updated boxed warning noting differentiation syndrome applies to AML and MDS; references reviewed and updated.

OpenPayer

Clinical Policy: Ivosidenib (Tibsovo)

Coverage Criteria

Line of Therapy

Biomarker Requirements

Covered Regimens and Dosing

Coding

Provider Actions and Prior Authorization

Definitions and Safety Information

Revision History