CurrentCignaPolicy CNF514

Oncology – Iclusig Prior Authorization Policy - (CNF514)

Prior authorization policy describing coverage criteria, duration, and non-covered uses for Iclusig (ponatinib tablets) across FDA-approved indications and select other uses with supportive evidence for Cigna-administered health benefit plans.

Policy Summary

PayerCigna

PolicyOncology – Iclusig Prior Authorization Policy - (CNF514)

Policy CodePolicy CNF514

Change TypeMaterial updates to ALL and CML criteria; GIST therapy list revised

Effective Date

Next Review Date

Key ActionPrior Authorization is recommended; document diagnosis, mutation status, prior TKI trials, and use with chemotherapy when applicable.

SourceLink

POLICY UPDATE CHANGES

An option for approval in ALL was added that states the medication will be used in combination with chemotherapy.

Age requirement and prior-TKI trial counts for ALL and CML were modified across earlier revisions (e.g., ≥15 removed; 'two' TKIs changed to 'one').

GIST prior therapy list was updated (Ayvakit and dasatinib removed).

4Covered Indications (listed)

1 yearApproval Duration

T315IMutation-based approval cited

Coverage stance: covered_with_criteria; Approval duration for listed indications: 1 year.

FDA-Approved Indications - Acute Lymphoblastic Leukemia (ALL)

Approve for 1 year if the patient meets BOTH of the following (A, and B):

ALL of the following

A
- Patient has Philadelphia chromosome-positive acute lymphoblastic leukemia
- Patient has ABL-class translocation
B
- The medication will be used in combination with chemotherapy
- The acute lymphoblastic leukemia is T315I-positive
- Patient has tried at least one other tyrosine kinase inhibitor
  Examples include imatinib and dasatinib

FDA-Approved Indications - Chronic Myeloid Leukemia (CML)

Approve for 1 year if the patient meets ALL of the following (A, B, and C):

ALL of the following

A: Patient is ≥ 18 years of age
Age requirement applies to this CML indication
B
- Patient has Philadelphia chromosome-positive chronic myeloid leukemia
- Patient has BCR::ABL1-positive chronic myeloid leukemia
C
- The chronic myeloid leukemia is T315I-positive

Other Uses with Supportive Evidence - Gastrointestinal Stromal Tumor (GIST)

Approve for 1 year if the patient meets BOTH of the following (A and B):

ALL of the following

A: Patient is ≥ 18 years of age
B
- B.i: Patient has tried imatinib
- B.ii: Patient has tried sunitinib
- B.iii: Patient has tried Stivarga (regorafenib tablets)

Other Uses with Supportive Evidence - Myeloid/Lymphoid Neoplasms with Eosinophilia

Approve for 1 year if the patient meets BOTH of the following (A and B):

ALL of the following

A: Patient is ≥ 18 years of age
B
- B.i: The tumor has an ABL1 rearrangement
- B.ii: The tumor has an FGFR1 rearrangement

ref": "b0_4

Conditions Not Covered

Not medically necessary when criteria are not met

Iclusig (ponatinib) is considered not medically necessary for ANY other use(s) not specified above

Provider Requirements & Billing Impact

Prior Authorization

Prior authorization required

Prior Authorization is recommended for prescription benefit coverage of Iclusig; approvals are provided for the duration noted (1 year for listed indications).

Documentation Required

Clinical documentation required to demonstrate criteria

Providers must document diagnosis, mutation status (e.g., T315I, ABL1 or FGFR1 rearrangement), prior TKI trials, and use with chemotherapy when applicable to meet the specific indication criteria.

Denial Risk

Claims may be denied if criteria not met

Claims submitted for services not accompanied by covered diagnosis codes under the applicable coverage policy will be denied as not covered.

Evidence & Rationale

Evidence includes: Package Insert: Iclusig tablets [prescribing information], ARIAD/Takeda; October 2025 and NCCN Guideline Versions Cited: Multiple NCCN guideline versions (2025-2026) supporting use in listed indications.

The background and history note the accelerated approval context for the newly diagnosed Ph+ ALL indication when Iclusig is used in combination with chemotherapy based on MRD‑negative complete remission at the end of induction.

Key policy evidence highlights

Regulatory contextPh+ ALL newly diagnosed use with chemotherapy approved under accelerated approval based on MRD-negative CR at end of induction; continued approval may require confirmatory trials

Prescribing info (date)Iclusig tablets prescribing information, ARIAD/Takeda; October 2025

Not indicated forNewly diagnosed chronic phase CML (limitation of use)

Guideline supportNCCN guidelines (2025–2026 versions) recommend Iclusig for T315I and select Ph+ disease settings and for use in combination regimens for Ph+ ALL

Policy changes (2024–2025)Age and prior‑TKI trial requirements were revised (e.g., ≥15 removed; ‘two’ TKIs changed to ‘one’); ABL‑class translocation added; option added for combination with chemotherapy

Background & Definitions

Iclusig (ponatinib) is a tyrosine kinase inhibitor with FDA indications for Philadelphia chromosome‑positive (Ph+) acute lymphoblastic leukemia (ALL) — including newly diagnosed Ph+ ALL in combination with chemotherapy and T315I‑positive ALL — and for chronic myeloid leukemia (CML), including T315I‑positive disease and accelerated‑ or blast‑phase CML when no other TKIs are indicated. The policy notes a limitation that Iclusig is not indicated for newly diagnosed chronic phase CML.

NCCN guideline recommendations are referenced for ALL, CML, GIST, and myeloid/lymphoid neoplasms with eosinophilia, and the policy history documents that the option to use Iclusig in combination with chemotherapy for newly diagnosed Ph+ ALL was added following a new FDA labeled indication (accelerated approval).

Term	Definition
T315I-positive	Presence of the T315I mutation in BCR-ABL1 conferring resistance to certain TKIs.
ABL-class translocation	Genetic rearrangements involving ABL-class genes relevant to ALL and other neoplasms.

Policy Revision Timeline

material - added

Based on new FDA labeled indication in newly diagnosed Philadelphia chromosome-positive ALL in combination with chemotherapy. An option for approval in ALL was added that states the medication will be used in combination with chemotherapy.

03/27/2024material - revised

Multiple historical revisions adjusted age and prior TKI trial requirements and added ABL-class translocation option; age requirement changed (≥18 to ≥15 in one revision), and the prior-TKI trial count was modified (two TKIs changed to one).

03/26/2025material - revised

Annual revision removed the ≥15 years age requirement and added 'patient has ABL-class translocation' as an approval option for ALL; other wording clarifications to prior TKI requirements and example TKIs were made.

05/14/2025material - revised

Selected revision changed the CML option for prior TKI trials from 'two other tyrosine kinase inhibitors' to 'one other tyrosine kinase inhibitor.'

03/25/2026revisedLatest

Annual revision updated GIST prior therapy list by removing Ayvakit (avapritinib) and dasatinib.

OpenPayer

Oncology – Iclusig Prior Authorization Policy - (CNF514)

Coverage Summary & Criteria

Applicable Codes

Provider Requirements & Billing Impact

Evidence & Rationale

Background & Definitions

Policy Revision Timeline