Centene Ponatinib (Iclusig) Coverage Update

Coverage Criteria for Ponatinib (Iclusig)

Initial Therapy — Chronic phase CML

Covered when ALL of the following are met:

Initial chronic phase CML criteria: 1) Diagnosis of Philadelphia chromosome‑positive (BCR‑ABL1‑positive) chronic myeloid leukemia (chronic phase); 2) Prescribed by or in consultation with an oncologist or hematologist; 3) Member is an adult (age documented per request); 4) Member has experienced resistance, toxicity, or intolerance to at least two other tyrosine kinase inhibitors (examples: imatinib, bosutinib, dasatinib, nilotinib); 5) Requested daily dose does not exceed 45 mg per day (one tablet per day) unless dose is supported by practice guidelines or peer‑reviewed literature (prescriber must submit supporting evidence); 6) For brand requests, member must use generic ponatinib if available unless contraindicated or clinically significant adverse effects are experienced; 7) BCR‑ABL T315I mutation is an allowable indication and may bypass prior‑TKI requirements where applicable.

Initial Therapy — Accelerated/blast phase CML and Ph+ ALL

Covered when ALL of the following are met:

Accelerated/blast phase CML or Ph+ ALL: 1) Diagnosis of accelerated phase or blast phase chronic myeloid leukemia (CML) OR Philadelphia chromosome‑positive (BCR‑ABL1‑positive) acute lymphoblastic leukemia (Ph+ ALL); 2) Prescribed by or in consultation with an oncologist or hematologist; 3) For accelerated/blast phase CML: member is eligible when no other TKI therapy is indicated; 4) For Ph+ ALL: when used for newly diagnosed disease in combination with chemotherapy follow the dosing limits for combination use (see dosing criteria); 5) Requested dose does not exceed 45 mg per day for indications other than newly diagnosed Ph+ ALL in combination with chemotherapy; 6) For newly diagnosed Ph+ ALL in combination with chemotherapy the dose limit is 30 mg per day; 7) For brand requests, member must use generic ponatinib if available unless contraindicated; 8) Prescriber may need to provide supporting literature for relevant off‑label requests or dose selections.

Initial Therapy — Myeloid/Lymphoid Neoplasms (off‑label)

Covered when ALL of the following are met:

MLNE with eosinophilia and FGFR1 or ABL1 rearrangement: 1) Diagnosis of a lymphoid, myeloid, or mixed‑lineage neoplasm with eosinophilia and FGFR1 or ABL1 rearrangement (blast or chronic phase); 2) Prescribed by or in consultation with an oncologist or hematologist; 3) Member is >18 years of age; 4) If ABL1 rearrangement positive, member has contraindication, intolerance, or disease progression on imatinib OR the request is for treatment in a state with regulations prohibiting oncology step therapy (see Appendix E for state exceptions); 5) Dose is within FDA maximum limits for approved indications or is supported by practice guidelines or peer‑reviewed literature (prescriber must submit supporting evidence); 6) For brand requests, member must use generic ponatinib if available unless contraindicated or clinically significant adverse effects are experienced.

Initial Therapy — Gastrointestinal Stromal Tumor (off‑label)

Covered when ALL of the following are met:

GIST criteria: 1) Diagnosis of gastrointestinal stromal tumor (GIST); 2) Prescribed by or in consultation with an oncologist; 3) Member is ≥18 years of age; 4) Prescribed as a single agent; 5) Documented failure of prior therapies (imatinib, ripretinib, sunitinib, or regorafenib) unless clinically significant adverse effects or contraindications to those agents exist; 6) Dose is within FDA maximum limits for any approved indication or is supported by practice guidelines or peer‑reviewed literature (prescriber must submit supporting evidence); 7) For brand requests, member must use generic ponatinib if available unless contraindicated or clinically significant adverse effects are experienced; 8) Prescribed regimen must be FDA‑approved or recommended by the NCCN Drugs & Biologics Compendium.

Continuation Therapy

Covered when ALL of the following are met:

Continued therapy criteria: 1) Member is currently receiving ponatinib via the Centene benefit, or documentation supports current use for a covered indication with at least 30 days of prior therapy; 2) Member is demonstrating clinical response or benefit on therapy; 3) If the request is for a dose increase, the new dose must not exceed 30 mg/day for newly diagnosed Ph+ ALL in combination with chemotherapy or 45 mg/day for all other indications unless the higher dose is supported by practice guidelines or peer‑reviewed literature (prescriber must submit supporting evidence); 4) For brand requests, member must use generic ponatinib if available unless contraindicated or clinically significant adverse effects are experienced; 5) Approval duration is consistent with benefit type (Medicaid/HIM 12 months; Commercial 12 months or duration requested, whichever is less).

Indication-specific coverage criteria

Covered when criteria specific to indication, prior TKI exposure or mutation status, and dosing requirements are met

Chronic phase CML indication-specific: Member has chronic phase CML AND has experienced resistance, toxicity, or intolerance to two or more prior TKIs (examples: imatinib, bosutinib, dasatinib, nilotinib). Per policy and NCCN guidance the 2‑TKI requirement applies to chronic phase CML.

T315I mutation or no other TKI option: Member has documented BCR‑ABL1 T315I mutation OR no other TKI therapy is indicated (this allows bypassing the prior‑TKI requirement in appropriate accelerated/blast phase CML or certain ALL contexts).

Newly diagnosed Ph+ ALL dosing and MRD: For newly diagnosed Ph+ ALL when used in combination with chemotherapy: start ponatinib 30 mg PO once daily with chemotherapy and reduce to 15 mg PO once daily upon achievement of MRD‑negative complete remission (MRD defined as <0.01% BCR‑ABL1/ABL1). Prescribing information recommends continuation for up to 20 cycles or until loss of response or unacceptable toxicity; NCCN notes optimal duration is unknown.MRD <0.01%

Off-label / compendium-driven criteria

Covered off-label uses per NCCN Compendium under specified criteria

GIST off-label: Off‑label use in gastrointestinal stromal tumor (GIST) per the NCCN Drugs & Biologics Compendium may be covered when the criteria in the GIST section are met (prior failure of indicated agents, prescriber specialty, adult age, single‑agent use, dosing supported by guidance or literature).

ABL1 rearrangement redirection: For lymphoid, myeloid, or mixed‑lineage neoplasms with ABL1 rearrangement, redirection to imatinib is applied (step therapy) unless state regulations prohibit oncology step therapy; if redirected, member must have contraindication, intolerance, or progression on imatinib to qualify for ponatinib for ABL1 rearrangement–positive disease. See Appendix E for state exceptions.

Requests for uses that are non‑FDA approved and not specifically addressed in this policy are not authorized unless the provider submits sufficient documentation demonstrating efficacy and safety in accordance with the applicable off‑label use policies (for example, CPCPA.09 for Commercial or HIM.PA.154 for Health Insurance Marketplace).

Ponatinib carries boxed warnings for serious adverse events including arterial occlusion, venous thromboembolism, heart failure, and hepatotoxicity. These safety concerns should be considered when evaluating therapy and documented in the clinical record when relevant to the coverage decision.

Use of ponatinib for indications that are not FDA‑approved and are not addressed in this policy is considered not covered unless the request is supported by adequate clinical documentation per the plan’s off‑label use policies.

Requests may be considered not medically necessary when the member does not meet the policy’s required prior‑TKI failure or mutation‑based criteria for the specific disease phase. For example, chronic‑phase CML generally requires documented resistance, intolerance, or toxicity to two or more prior TKIs unless an exception (such as the presence of the BCR‑ABL T315I mutation or situations where no other TKI is indicated) applies.

Dosing and Regimen Guidance

Regimen	Indication / Notes	Dose / Administration	Coverage Status
Ponatinib in combination with chemotherapy
Newly diagnosed Philadelphia chromosome–positive acute lymphoblastic leukemia (Ph+ ALL) when used with multi-agent chemotherapy
Start 30 mg PO once daily in combination with chemotherapy; reduce to 15 mg PO once daily upon achievement of MRD‑negative (<0.01% BCR‑ABL1/ABL1) complete remission; continuation per prescribing information up to 20 cycles or until loss of response/unacceptable toxicity
Covered with criteria

Regimen	Indication / Notes	Dose / Administration	Coverage Status
Ponatinib general dosing
Other CML indications and Ph+ ALL requests not in combination-newly diagnosed chemotherapy context; includes accelerated/blast phase and monotherapy uses
Up to 45 mg PO once daily (one tablet per day) unless a guideline- or literature-supported alternative dosing is provided
Covered with criteria

Regimen	Indication / Notes	Dose / Administration	Coverage Status
Chronic phase CML regimen
Chronic phase chronic myeloid leukemia (BCR‑ABL1‑positive) typically after resistance/intolerance to ≥2 TKIs or per criteria; T315I mutation noted as an indication
Start 45 mg PO once daily; reduce to 15 mg PO once daily upon achievement of <1% BCR‑ABL1; patients with loss of response may re‑escalate to a previously tolerated dose; maximum dose 45 mg/day
Covered with criteria

Regimen	Indication / Notes	Dose / Administration	Coverage Status
Newly diagnosed Ph+ ALL (with chemotherapy) regimen
Philadelphia chromosome–positive acute lymphoblastic leukemia when administered in combination with chemotherapy (per prescribing information; FDA accelerated approval context)
Start 30 mg PO once daily with chemotherapy; reduce to 15 mg PO once daily upon achievement of MRD‑negative (<0.01% BCR‑ABL1/ABL1) complete remission at end of induction; continue per prescribing information (up to 20 cycles or until loss of response/unacceptable toxicity)
Covered with criteria

Regimen	Indication / Notes	Dose / Administration	Coverage Status
Accelerated or blast phase CML regimen
Accelerated phase or blast phase chronic myeloid leukemia; may be used when no other TKI is indicated
Starting dose 45 mg PO once daily; consider dose reductions for toxicity or tolerability; maximum 45 mg/day
Covered with criteria

Permitted Lines of Therapy

second-line | later-line | first-line (specific for newly diagnosed Ph+ ALL with chemo)

second-line | later-line | first-line (Ph+ ALL specific): Used as later‑line therapy for chronic phase CML after failure/intolerance to ≥2 TKIs; may be used in accelerated/blast phase CML when no other TKI is indicated; indicated for newly diagnosed Ph+ ALL in combination with chemotherapy (accelerated approval) — see dosing criteria for newly diagnosed Ph+ ALL.

second-line

Second-line: For chronic phase CML, use is allowed after resistance, toxicity, or intolerance to two or more TKIs; documentation of prior TKI history and responses is required.

salvage

Salvage:

Required Biomarkers and Definitions

inv-28: BCR-ABL T315I — biomarker requirement

BiomarkerBCR-ABL T315I mutation (T315I)

PurposePermits coverage pathway that may bypass prior‑TKI requirements for CML when present

Documentation requiredClinical laboratory report or molecular testing demonstrating presence of BCR-ABL T315I

inv-29: BCR-ABL1 T315I — biomarker requirement

BiomarkerBCR-ABL1 T315I mutation

Policy roleAllows coverage without the 2‑TKI failure requirement in certain CML/ALL contexts when present

Required evidence

Prior Authorization, Documentation, and Provider Requirements

Prior Authorization

Prior Authorization and Required Documentation

Prior authorization is required. Provider must submit supporting clinical documentation (e.g., office chart notes, relevant laboratory results, pathology or molecular testing reports) demonstrating the member meets all approval criteria.

Prescriber must document BCR‑ABL1 mutation status (e.g., T315I) when relevant.
Include prior TKI therapy history with dates, doses, response, and reason for discontinuation (resistance, intolerance, toxicity, or progression).

Documentation Required

Prescriber Specialty Requirement

Requests must be prescribed by or in consultation with an oncologist or hematologist for all covered indications.

Background

Ponatinib (Iclusig) is an oral tyrosine kinase inhibitor indicated for certain adults with chronic myeloid leukemia (CML) and Philadelphia chromosome‑positive acute lymphoblastic leukemia (Ph+ ALL), including patients with the BCR‑ABL T315I mutation. Dosing varies by indication (commonly up to 45 mg daily for many CML/Ph+ ALL indications and up to 30 mg daily when used in newly diagnosed Ph+ ALL in combination with chemotherapy per prescribing information). The drug’s safety profile includes boxed warnings for arterial occlusion, venous thromboembolism, heart failure, and hepatotoxicity, which should be weighed against clinical benefit when authorizing therapy.

Definitions and Abbreviations

inv-22: Pht / Ph+ — Philadelphia chromosome‑positive definition.

TermPht / Ph+

DefinitionPhiladelphia chromosome‑positive (presence of the BCR-ABL fusion)

ContextUsed to identify CML and Ph+ ALL diagnoses within policy criteria

inv-23: MRD-negative defined as <0.01% BCR-ABL1/ABL1.

TermMRD-negative (BCR-ABL1/ABL1)

Numeric threshold<0.01% BCR-ABL1/ABL1

Use in dosing decisionsTrigger for reducing ponatinib from 30 mg to 15 mg PO QD in newly diagnosed Ph+ ALL when achieved at end of induction

Policy Revision History

2025-05-25annual_reviewLatest

2Q 2025 annual review: added option per NCCN for combination use with corticosteroid in newly diagnosed ALL and added pediatric (<18 years) use option for relapsed/refractory BCR-ABL1–positive B‑cell ALL or T‑cell ALL with ABL-class translocation; references updated.

2024-06-05appendix_update

Updated Appendix E to include Mississippi and made related state-level redirection/step-therapy notes updates.

2024-03-27

OpenPayer

Ponatinib (Iclusig) — Coverage Criteria

Coverage Criteria for Ponatinib (Iclusig)

Dosing and Regimen Guidance

Permitted Lines of Therapy

Required Biomarkers and Definitions

Prior Authorization, Documentation, and Provider Requirements

Background

Definitions and Abbreviations

Policy Revision History