CurrentNeighborhood Health Plan of Rhode IslandPolicy N/A

Komzifti

Defines accepted indications, contraindications, exclusion criteria, required supporting evidence, and coding for ziftomenib (Komzifti) use in adults with relapsed/refractory acute myeloid leukemia (AML) with NPM1 mutation. Specifies treatment duration guidance, monitoring warnings, and utilization management responsibilities.

Policy Summary

PayerNeighborhood Health Plan of Rhode Island

PolicyKomzifti

Policy CodePolicy N/A

Change TypeNew policy

Effective Date

Next Review Date

Key ActionEvolent processes all medication requests; continuation requests meeting continuity criteria are exempt from this policy requirement.

SourceLink

POLICY UPDATE CHANGES

New policy created (Policy history notes December 2025: New policy).

1Covered Indications (FDA-approved listed)

6Key exclusion criteria items

1HCPCS drug code listed

Coverage Summary

Coverage stance: Komzifti (ziftomenib) is covered with criteria for adult patients with relapsed or refractory acute myeloid leukemia (AML) harboring a susceptible NPM1 mutation. Evolent manages all medication requests and prior authorization; continuation requests may be exempt if continuity criteria are met.

Initial Therapy Criteria and Continuation Criteria

Medically Necessary / Initial and Continuation Therapy

Komzifti (ziftomenib) may be used when ALL of the following are met:

Member is an adult
Diagnosis of relapsed or refractory acute myeloid leukemia (AML)
Presence of a susceptible nucleophosmin 1 (NPM1) mutation
Documented NPM1 mutation is required
No satisfactory alternative treatment options
For members without confirmed disease progression or unacceptable toxicity, treatment is recommended for a minimum of 6 months to allow time for a clinical responseminimum 6 months

Continuation therapy exemption

Continuation requests are exempt from this Evolent policy provided ALL of the following are true:

Member has not experienced disease progression on the requested medication
Requested medication was used within the last year without a lapse of more than 30 days of having an active authorization<= 30 day lapse
No additional medications are being added to the continuation request

Exclusions, Limits, and Warnings

Exclusion / Not Medically Necessary Criteria

Treatment is NOT authorized when ANY of the following exclusion criteria apply:

Disease progression while taking Komzifti (ziftomenib)
Concurrent use with other anticancer therapies
Absence of documented NPM1 mutation
Document presence of a susceptible NPM1 mutation is required
Dosing exceeds single dose limit of 600 mgsingle dose > 600 mg
Treatment exceeds the maximum limit of Komzifti (ziftomenib) 90 (200 mg) capsules per monthmonthly > 90 (200 mg) capsules
Investigational-use off-label indication
- Insufficient evidence includes lack of CMS-recognized compendia or acceptable peer-reviewed literature
- Case reports or abstracts without full peer-reviewed articles are inadequate supportive evidence

Warnings / Management

Treatment requires monitoring and management according to warnings:

Differentiation syndrome management: Differentiation syndrome has occurred and can be fatal; if suspected, interrupt ziftomenib and initiate oral or IV corticosteroids, monitor hemodynamics and labs until symptoms resolve; resume upon improvement
US boxed warning
QTc management: QTc interval prolongation risk: monitor electrocardiograms and electrolytes; correct hypokalemia and hypomagnesemia prior to treatment; interrupt ziftomenib if QTc > 500 msQTc > 500 ms (interrupt)

Prior Authorization, Documentation, and Monitoring

Prior Authorization

Prior authorization required / Evolent processing

Evolent is responsible for processing all medication requests. Medications not authorized by Evolent may be deemed not approvable and not reimbursable. Continuation requests that meet the policy's continuity criteria (no disease progression on the medication, used within the last year without a lapse >30 days of active authorization, and no additional medications added) are exempt from prior authorization processing.

J8999

Documentation Required

Mutation documentation

Document in the medical record the presence of a susceptible NPM1 (nucleophosmin 1) mutation. Absence of a documented NPM1 mutation is an exclusionary criterion for treatment.

Documentation Required

Treatment duration documentation

For members without confirmed disease progression or unacceptable toxicity, document treatment intent and clinical response assessments to support continuing therapy for the policy-recommended minimum of 6 months to allow time for a clinical response.

Denial Risk

Exclusion triggers leading to denial

Claims may be denied when any exclusion criteria are met, including disease progression while on ziftomenib, concurrent use with other anticancer therapies, dosing or monthly capsule limits exceeded, or when off‑label use lacks sufficient supporting evidence in recognized compendia or peer-reviewed literature.

J8999
Disease progression while taking Komzifti (ziftomenib)
Concurrent use with other anticancer therapies
Single dose > 600 mg or monthly > 90 (200 mg) capsules
Off-label use lacking CMS-recognized compendia or acceptable peer‑reviewed evidence

Documentation Required

Monitoring requirements for safety

Monitor patients for differentiation syndrome and for QTc interval prolongation. If differentiation syndrome is suspected, interrupt ziftomenib and initiate oral or IV corticosteroids, monitor hemodynamics and labs until symptoms resolve, and resume when improved. Monitor electrocardiograms and electrolytes, correct hypokalemia and hypomagnesemia before treatment, and interrupt ziftomenib if QTc > 500 ms.

Background & Clinical Evidence

Accepted indications: Komzifti (ziftomenib) is accepted for use in adults with relapsed or refractory AML with a susceptible NPM1 mutation when no satisfactory alternative treatment options exist; treatment is recommended for a minimum of 6 months for members without confirmed progression or unacceptable toxicity. The policy defines FDA-approved labeling and allows off-label use only when supported by CMS-recognized compendia or acceptable peer‑reviewed literature. Evolent processes all medication requests and prior authorizations; medications not authorized by Evolent may be deemed not approvable and not reimbursable. Continuation requests are exempt when the member has not progressed, there was no lapse >30 days in authorization within the last year, and no additional medications are added.

Evidence references: KOMET-001 primary trial (Wang ES et al; KOMET-001. J Clin Oncol. 2025;43(31):3381-3390) and the Komzifti prescribing information (Kura Oncology, 2025) are cited as supporting evidence.

Revision History

December 2025policy_createdLatest

New policy created (Policy history notes December 2025: New policy).

coverage_stance_defined

Policy defines accepted indications for Komzifti (ziftomenib), including FDA-approved and off-label uses supported by recognized compendia or peer-reviewed literature; Evolent manages medication requests and prior authorization.

continuation_criteria

Continuation requests exempt from policy if member has no disease progression on medication, medication used within last year without >30-day lapse in authorization, and no additional medications are added.

Policy Summary

PayerNeighborhood Health Plan of Rhode Island

PolicyKomzifti

Policy CodePolicy N/A

Change TypeNew policy

Effective Date

Next Review Date

Key ActionEvolent processes all medication requests; continuation requests meeting continuity criteria are exempt from this policy requirement.

SourceLink

On This Page

OpenPayer

Komzifti

Coverage Summary

Initial Therapy Criteria and Continuation Criteria

Exclusions, Limits, and Warnings

Applicable Codes

Prior Authorization, Documentation, and Monitoring

Background & Clinical Evidence

Revision History