ModifiedPremera BluecrossPolicy N/A

BCR-ABL Kinase Inhibitors (Pharmacy Coverage Criteria)

Pharmacy benefit coverage criteria for BCR-ABL tyrosine kinase inhibitor medications used to treat Philadelphia chromosome–positive leukemias and related indications; intended for providers requesting coverage for these drugs.

Policy Summary

PayerPremera Bluecross

PolicyBCR-ABL Kinase Inhibitors (Pharmacy Coverage Criteria)

Policy CodePolicy N/A

Change TypeMultiple material revisions (criteria additions, step therapy clarification, authorization updates)

Effective DateMay 1, 2026

Next Review DateN/A

Key ActionWhen requesting coverage, document trial and failure of generic imatinib (where required) and submit medical records demonstrating that medical necessity criteria are met.

SourceLink

POLICY UPDATE CHANGES

Added coverage criteria for Phyrago (dasatinib).

Removed Synribo (omacetaxine) coverage criteria as it has been withdrawn from the market.

Clarified that the imatinib step therapy requirement is limited to generic imatinib for Sprycel, Scemblix, Tasigna, and Iclusig.

Updated Iclusig (ponatinib) to include coverage criteria for certain adults with newly diagnosed acute lymphoblastic leukemia.

Updated Gleevec criteria to require trial and failure to generic imatinib and added a new coverage criterion for generic imatinib.

Added coverage criteria for new products including Phyrago (dasatinib), Imkeldi (imatinib oral solution), Danziten (nilotinib), and generic formulations of dasatinib and nilotinib.

Updated initial authorization period for all 'other reviews' for all drugs listed in the policy from 3 months to 6 months.

Added imatinib step therapy requirement specifying trial/failure of generic imatinib for certain agents and limited the imatinib step requirement to generic imatinib.

Added documentation requirements table and clarified non-formulary exception reviews may be approved up to 12 months.

Updated quantity limit for brand nilotinib tartrate to 120 tablets per 30 days.

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multipleAgents listed

pharmacyBenefit

6 moInitial auth (other reviews)

120/30dNilotinib limit

multipleNew products added

Drug-Specific and General Coverage Criteria

Bosutinib (Bosulif) — Medical Necessity

Bosulif may be considered medically necessary when ONE of the following is met:

Bosulif indications: Treatment of adult individuals with accelerated or blast phase Philadelphia chromosome–positive chronic myeloid leukemia (Ph+ CML) with resistance or intolerance to prior therapy with generic imatinib; OR Treatment of individuals aged 1 year or older with chronic phase Ph+ CML when either newly diagnosed OR with resistance or intolerance to prior therapy with generic imatinib.

Individuals not demonstrating objective response to prior therapy after three months are considered resistant for purposes of prescribing an alternative therapy.

Nilotinib (Danziten/Tasigna) — Medical Necessity (brand and generic distinguished)

Nilotinib products may be considered medically necessary when ALL of the following are met (drug-specific conditions noted):

Danziten (brand nilotinib) adults: The individual is aged 18 years or older AND diagnosed with chronic, accelerated, or blast phase Philadelphia chromosome–positive chronic myeloid leukemia (Ph+ CML) AND has had resistance or intolerance to prior therapy with generic imatinib AND has had resistance or intolerance to prior therapy with generic nilotinib AND the quantity is limited to 120 tablets per 30 days.120 tablets/30 days

Individuals not demonstrating objective response to generic imatinib therapy after three months are considered imatinib-resistant for purposes of prescribing an alternative therapy.

Generic nilotinib: The individual has had resistance or intolerance to prior therapy with generic imatinib AND meets one of: treatment of adults with chronic, accelerated, or blast phase Ph+ CML; treatment of adults with Ph+ ALL; treatment of pediatric individuals 1 year or older with Ph+ CML in chronic phase.

Danziten (a re‑engineered formulation) and Tasigna share product‑specific requirements per prescribing information; generic nilotinib criteria include the listed indications.

Dasatinib (generic, Phyrago, Sprycel) — Medical Necessity

Dasatinib products may be considered medically necessary when ALL the following are met:

Generic dasatinib general: The individual has had resistance or intolerance to prior therapy with generic imatinib AND meets one of the following indications: treatment of newly diagnosed adults with Ph+ CML in chronic phase; treatment of adults with chronic, accelerated, or blast phase Ph+ CML; treatment of adults with Ph+ ALL; treatment of individuals with gastrointestinal stromal tumor (GIST); treatment of pediatric individuals with Ph+ CML in chronic phase.

Phyrago (dasatinib brand) additional requirements: The individual has had resistance or intolerance to prior therapy with generic imatinib AND has had resistance or intolerance to prior therapy with generic dasatinib OR has documented drug interactions with use of generic dasatinib (e.g., H2 antagonists, proton pump inhibitors) AND meets one of the listed indications (pediatric ≥1 year with Ph+ CML in chronic phase; newly diagnosed adults with Ph+ CML in chronic phase; adults with chronic/accelerated/blast phase Ph+ CML; adults with Ph+ ALL).

Phyrago used in combination with chemotherapy for Ph+ ALL and may be considered for pediatric Ph+ ALL when used with chemotherapy.

Sprycel (dasatinib): The individual has had resistance or intolerance to prior therapy with generic imatinib.

Ponatinib (Iclusig) — Medical Necessity

Iclusig (ponatinib) may be considered medically necessary when ALL the following are met:

Iclusig indications: The individual is aged 18 years or older AND meets one of the following: treatment of adults with chronic, accelerated, or blast phase Ph+ CML; OR treatment of adults with Ph+ ALL. (Policy notes ponatinib activity against the T315I mutation and includes coverage language for select newly diagnosed ALL adults per updates.)

Individuals not demonstrating objective response to generic imatinib therapy after three months are considered imatinib-resistant for purposes of prescribing an alternative therapy.

Asciminib (Scemblix) — Medical Necessity

Scemblix may be considered medically necessary for treatment of Ph+ CML when ALL the following are met:

Scemblix criteria: The individual is aged 18 years or older AND Ph+ CML is in chronic phase AND meets ONE of: newly diagnosed, previously treated, or is T315I‑positive AND the individual has had resistance or intolerance to prior therapy with generic imatinib.

Individuals not demonstrating objective response to generic imatinib therapy after three months are considered imatinib‑resistant for prescribing alternatives. 2025 updates expanded Scemblix criteria to include newly diagnosed individuals and previously treated individuals as specified.

Imatinib (Gleevec, Imkeldi) — Medical Necessity

Imatinib (brand and oral solution) may be considered medically necessary when one of the following is met:

Imatinib indications: Treatment of adult and pediatric individuals with Ph+ CML in chronic phase, accelerated phase, or blast crisis; treatment of pediatric individuals with recurrent Ph+ CML after stem cell transplant; treatment of adult and pediatric individuals with Ph+ ALL in combination with chemotherapy; and other FDA‑approved indications including PDGFR‑associated MDS/MPD, ASM (without D816V c‑Kit mutation or unknown), DFSP, KIT+ cancers and KIT+ GIST.

Imkeldi (imatinib oral solution) was added with the same coverage criteria as brand Gleevec. 2023 updates require trial and failure of generic imatinib before brand Gleevec in relevant indications.

Evidence and guideline alignment

Covered when aligned with accepted NCCN evidence levels and drug-specific labeled indications

Evidence-based coverage: Uses listed in the NCCN Drugs and Biologics Compendium with Category 1 or 2A evidence are recognized by the policy as proven and covered; uses supported only by Category 2B or 3 are considered unproven and may be denied unless the provider submits significant peer‑reviewed Phase II or Phase III studies demonstrating effectiveness.NCCN Category 1 or 2A

Per policy and CMS/NAS guidance described in the NCCN and CMS statements.

Drug-specific coverage

Coverage reflects FDA-labeled indications and subsequent policy updates

Agent-specific coverage: Policy includes coverage criteria for imatinib (brand and generic, including oral solution), dasatinib (generic, Phyrago, Sprycel), nilotinib (Tasigna, Danziten, generic), bosutinib (Bosulif), ponatinib (Iclusig), and asciminib (Scemblix) with pediatric and adult indications updated over time; ponatinib is specifically identified for T315I‑positive disease and select newly diagnosed ALL adults per updates.agent-specific labeling and age limits

See individual drug criteria sections for product‑specific requirements and age limits.

Step therapy / prior drug failure

Prior therapy requirements

Imatinib trial requirement: Prior trial and documented failure of generic imatinib is required before coverage of brand Gleevec; step therapy with generic imatinib is the specified requirement for Sprycel (dasatinib), Scemblix (asciminib), Tasigna/Danziten (nilotinib), and Iclusig (ponatinib) where indicated.trial and documented failure of generic imatinib

Policy updates clarified the imatinib step therapy requirement is limited to generic imatinib; some agents also require prior trial/failure of generic dasatinib or generic nilotinib per product criteria.

Product-specific medical necessity

Covered when product-specific FDA-labeled indications and policy criteria are met; includes step therapy and prior therapy/resistance/intolerance requirements as specified per product.

Product-specific coverage: Coverage requires meeting the product's FDA dosage and administration prescribing information and applicable policy requirements such as prior trial/failure of generic imatinib or other specified agents, documented resistance or intolerance where required, and age indications (including pediatric age ≥1 year where specified).

Applies to listed agents including brand and generic products added in updates (e.g., Phyrago, Imkeldi, Danziten, generic dasatinib/nilotinib).

All uses of the medications listed in this policy that are not specifically included in the product-specific coverage criteria are considered investigational. The medications in this policy are subject to the product's FDA dosing and administration labeling, and coverage for non-formulary or off-label uses is only considered when those uses meet the policy's medical necessity criteria and supporting evidence requirements.

Synribo (omacetaxine) coverage criteria have been removed from this policy because the product has been withdrawn from the market.

Synribo (omacetaxine) coverage criteria have been removed from this policy due to market withdrawal of the product.

Uses supported only by NCCN Category 3 are considered not medically accepted. Uses supported by NCCN Category 2B are treated as unproven unless the provider supplies significant peer-reviewed Phase II or Phase III studies demonstrating effectiveness; absent such evidence, Category 2B uses may be considered not medically necessary.

This medical policy does not apply to Medicare Advantage members. Coverage for any drug or service remains subject to the limits and conditions of the member's benefit plan; providers and members should consult the member benefit booklet or customer service for applicable benefit limitations.

Billing and Coding References

Coding notemixed

No codes listed

Historical HCPCS codes mentioned in policy historyHCPCS

C9297	HCPCS code referenced previously in history
9399	HCPCS code referenced previously in history
J9999	HCPCS code referenced previously in history

Prior Authorization, Documentation, and Operational Rules

Prior Authorization

Pharmacy benefit prior authorization and authorization duration

Coverage for the drugs in this policy is managed through the pharmacy benefit. Prior authorization and non-formulary exception reviews may be requested through the pharmacy benefit; non-formulary exception reviews may be approved for up to 12 months.

Pharmacy benefit management: all drugs listed in this policy
Non-formulary exception authorization duration: up to 12 months

Prior Authorization

Authorization duration and exceptions

Initial authorizations for 'all other reviews' for drugs listed in this policy have been updated to 6 months. Re-authorization and non-formulary exception reviews may be approved up to 12 months provided drug-specific coverage criteria are met and chart notes document continued positive clinical response.

Initial authorization for 'all other reviews': 6 months
Re-authorization and non-formulary exception: may be approved up to 12 months if criteria met and documentation supports continued response

Clinical Background and Scope

BCR‑ABL is a fusion gene created by translocation of parts of chromosomes 9 and 22; it produces a constitutively active tyrosine kinase that drives chronic myelogenous leukemia (CML) and some other malignancies. BCR‑ABL tyrosine kinase inhibitors (TKIs) target this abnormal protein and are the foundation of therapy for Philadelphia chromosome–positive leukemias. First‑line therapy historically has been imatinib, with second‑ and third‑generation TKIs used for disease resistant to imatinib or when specific resistance mutations (for example, T315I) are present. Mutation testing (sequencing, PCR, and other methods) can guide selection of alternative TKIs, but test sensitivity and clinical utility vary and should be interpreted in the context of the clinical picture.

Key Terms and Mutations

BCR-ABL — definition and relevance

DefinitionBCR-ABL: a fusion gene from translocation of chromosomes 9 and 22 producing a constitutively active tyrosine kinase that drives chronic myelogenous leukemia (CML) and other Philadelphia chromosome–positive malignancies.

Molecular consequenceCreates a constitutively active BCR-ABL tyrosine kinase (p210 or p185) that accelerates cell division and inhibits DNA repair.

Therapeutic relevanceBCR-ABL is the direct target of BCR-ABL tyrosine kinase inhibitors (TKIs) including imatinib, dasatinib, nilotinib, bosutinib, ponatinib, and asciminib.

Clinical implicationDetection of BCR-ABL defines Philadelphia chromosome–positive disease (Ph+ CML and Ph+ ALL) and guides use of targeted TKIs.

Testing noteMutation testing of BCR-ABL kinase domain can inform selection of second- and third-generation TKIs when resistance occurs.

Policy Updates and Material Changes

2009-12-08administrative_update

Policy replaced with additional wording regarding NCCN added to Description and Rationale (no change to policy statements).

2018-05-01annual_review

Annual review with literature search and updates to pediatric indication on dasatinib and revised table wording.

2019-01-01annual_review

Reviewed prescribing information and updated Tasigna (nilotinib) criteria for pediatric use greater than specified age.

Policy Summary

PayerPremera Bluecross

PolicyBCR-ABL Kinase Inhibitors (Pharmacy Coverage Criteria)

Policy CodePolicy N/A

Change TypeMultiple material revisions (criteria additions, step therapy clarification, authorization updates)

Effective DateMay 1, 2026

Next Review DateN/A

Key ActionWhen requesting coverage, document trial and failure of generic imatinib (where required) and submit medical records demonstrating that medical necessity criteria are met.

SourceLink

On This Page

Step Therapy

Required prior therapy (step) and Generic imatinib step

Many target agents require documented prior trial and either intolerance or resistance to generic imatinib before coverage of alternatives will be considered. The imatinib step requirement is specifically limited to trials of generic imatinib (and where applicable generic dasatinib/nilotinib) as noted below. Providers must document prior therapy trials, duration, and reason for discontinuation (e.g., intolerance or objective resistance).

Step therapy requirement: trial and failure (resistance or intolerance) of generic imatinib required for many second-line agents
Specific agents with imatinib-generic step: Sprycel (dasatinib), Scemblix (asciminib), Tasigna (nilotinib), Iclusig (ponatinib), Bosulif (bosutinib), Phyrago (dasatinib), generic dasatinib, generic nilotinib, Gleevec/Imkeldi (imatinib products) where applicable

Step Therapy

Imatinib / Generic imatinib step therapy requirement

Imatinib (generic) step therapy: the policy requires trial and documented failure (resistance or intolerance) of generic imatinib prior to coverage of specified alternatives. This imatinib step requirement is explicitly limited to generic imatinib products; documentation should indicate dates, dose, duration (note: lack of objective response after three months is considered resistance for purposes of the policy), and reason for discontinuation.

Imatinib step limited to generic imatinib (not brand-only requirement)
Objective nonresponse after 3 months = considered resistant
Document trial details: dates, formulations, doses, duration, and reason for failure/intolerance

Documentation Required

Prior therapy documentation

Prior therapy documentation must be provided when a step-therapy requirement is part of the coverage criteria. Providers should submit medical records demonstrating the trial and failure (resistance or intolerance) to the required prior agent(s) — for example, generic imatinib, and where applicable generic dasatinib or generic nilotinib.

Provide objective documentation of prior trials: medication name (generic), start and stop dates, doses, and reason for discontinuation
If claiming resistance, include objective response data or note that lack of response after 3 months is considered resistance

Denial Risk

Documentation-related denials and denial triggers

Failure to provide required documentation that medical necessity criteria are met may result in denial. Required records include office visit notes with diagnosis, relevant history, physical evaluation, medication history, and supporting labs/pathology as applicable. Incomplete documentation of prior trials (drug name, dates, dose, duration, and reason for failure) or absence of evidence of resistance/intolerance to the required generic agent(s) are common denial triggers.

Required records: office visit notes, diagnosis, history, physical exam, medication history, labs, pathology/histology when applicable
Denial triggers: missing documentation of trial/failure of generic imatinib (or generic dasatinib/nilotinib when required), missing dates/doses/duration, or lack of objective evidence of resistance/intolerance

T315I mutation — resistant to most TKIs except ponatinib; testing notes

Mutation identityT315I: a point mutation in the BCR-ABL kinase domain associated with high-level resistance to most available TKIs.

Clinical significanceThe T315I mutation is resistant to all TKIs except ponatinib; ponatinib has significant activity against T315I-positive disease.

Testing methodsA rapid PCR method is available to detect the T315I mutation; other mutation-detection methods (sequencing, mass spectrometry, D-HPLC) are also used.

Guiding therapyIdentification of T315I should prompt consideration of ponatinib (Iclusig) per policy coverage for T315I-positive Ph+ CML and Ph+ ALL.

Primary resistance — definition and timing (failure to achieve remission in 3–6 months)

DefinitionPrimary resistance: failure to achieve remission within 3 to 6 months of initial imatinib therapy.

CausesMay be due to excessive plasma protein binding of imatinib or reduced drug transport into cells.

Clinical thresholdIndividuals not demonstrating objective response to imatinib after three months are considered resistant for purposes of prescribing an alternative therapy (per drug-specific notes).

ImplicationPrimary resistance supports evaluation for alternative BCR-ABL inhibitors or further diagnostic workup including mutation testing.

Secondary resistance — acquired kinase domain mutations leading to loss of response

DefinitionSecondary resistance: loss of response to therapy due to acquired mutations in the BCR-ABL kinase domain after an initial response.

MechanismMost commonly caused by acquired mutations in the drug-binding site of the BCR-ABL protein.

Clinical consequenceLeads to treatment failure on the initially effective TKI and often requires mutation testing to select an alternative inhibitor.

DetectionMutation detection rates vary by method; sequencing, mass spectrometry, and D-HPLC can detect acquired mutations that guide therapy choice.

T315I mutation (alternate entry) — notes on ponatinib activity

Ponatinib activityPonatinib (Iclusig) is the only TKI with significant activity against the T315I mutation.

Clinical coveragePolicy was updated to add Iclusig coverage for T315I-positive Ph+ CML and T315I-positive Ph+ ALL (2021 update).

Therapeutic roleConsider ponatinib for patients with T315I-positive disease when mutation testing identifies T315I.

Ph+ CML and Ph+ ALL — condition labels

Condition labelsPhiladelphia chromosome–positive chronic myeloid leukemia (Ph+ CML)

Related conditionPhiladelphia chromosome–positive acute lymphoblastic leukemia (Ph+ ALL)

Usage contextPolicy criteria and FDA-labeled indications apply to these Ph+ diseases for listed BCR-ABL inhibitors across adult and pediatric age categories as specified per agent.

2021-01-01coverage_extension

Added ponatinib (Iclusig) coverage for T315I–positive Ph+ CML and T315I–positive Ph+ ALL.

2023-01-01step_therapy_revision

Updated Gleevec (imatinib) criteria to require trial and failure of generic imatinib and added a new coverage criterion for generic imatinib.

2024-01-01product_addition_and_removal

Added coverage criteria for Phyrago (dasatinib) and removed Synribo (omacetaxine) coverage criteria after market withdrawal; clarified imatinib step therapy is limited to generic imatinib and extended Iclusig coverage to certain newly diagnosed adult ALL patients.

2025-03-01annual_review

Annual review approved Feb 11, 2025; updated Bosulif (bosutinib) criteria to specify prior therapy requirements.

2025-08-01product_and_quantity_updates

Interim review approved July 8, 2025: added coverage criteria for generic nilotinib and updated Danziten (brand nilotinib) quantity limit language.

2026-05-01authorization_and_quantity_revisionLatest

Effective 2026-05-01: initial authorization for all 'other reviews' extended to 6 months and quantity limit for brand nilotinib tartrate set to 120 tablets per 30 days; policy effective/last reviewed 2026-05-01.