CurrentAnthemPolicy CC-0132

Mylotarg (gemtuzumab ozogamicin) — Coverage Criteria

Clinical coverage criteria for use of Mylotarg (gemtuzumab ozogamicin) for acute myeloid leukemia (AML) and acute promyelocytic leukemia (APL) under the medical benefit, including prior authorization requirements for induction, consolidation, and relapsed/refractory settings.

Policy Summary

PayerAnthem

PolicyMylotarg (gemtuzumab ozogamicin) — Coverage Criteria

Policy CodePolicy CC-0132

Change TypeMaterial clinical update (APL indication added)

Effective Date04/01/2025

Next Review Date

Key ActionObtain prior authorization; requests will be reviewed against clinical criteria specifying CD33+ AML or APL and the treatment setting.

SourceLink

POLICY UPDATE CHANGES

Update APL NCCN criteria to include use in leukocytosis associated with APL differentiation syndrome as a single agent.

1HCPCS code listed for Mylotarg

C92.00-C94.22ICD-10 diagnosis ranges included

Hepatotoxicity/VODBlack box

2ANCCN evidence category

Coverage Criteria for Mylotarg (gemtuzumab ozogamicin)

Policy Summary

PayerAnthem

PolicyMylotarg (gemtuzumab ozogamicin) — Coverage Criteria

Policy CodePolicy CC-0132

Change TypeMaterial clinical update (APL indication added)

Effective Date04/01/2025

Next Review Date

Key ActionObtain prior authorization; requests will be reviewed against clinical criteria specifying CD33+ AML or APL and the treatment setting.

SourceLink

On This Page

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AML — Initial/Consolidation/Relapsed

Requests for Mylotarg may be approved when ALL of the following are met (for AML).

AML general: Individual has a diagnosis of CD33+ acute myeloid leukemia (AML)

Chunk supports CD33+ AML requirement

AML settings: Individual is using for one of the following: induction for AML; OR consolidation therapy for AML; OR treatment for relapsed or refractory AML

Induction, consolidation, or relapsed/refractory are acceptable settings

APL — NCCN 2A specified uses

Requests for Mylotarg may be approved when ALL of the following are met (for APL per NCCN 2A).

APL diagnosis: Individual has a diagnosis of acute promyelocytic leukemia (APL) with NCCN 2A support

Document references NCCN 2A level for APL uses

APL acceptable uses: High-risk APL (white blood cell count > 10,000/mcL); OR low-risk APL (white blood cell count ≤ 10,000/mcL) when arsenic is not available or is contraindicated; OR relapsed APL; OR leukocytosis associated with APL differentiation syndrome when used as a single agent> 10,000/mcL for high-risk; ≤ 10,000/mcL defines low-risk

Multiple alternative APL indications per NCCN 2A

Requests for Mylotarg (gemtuzumab ozogamicin) will be denied when the patient does not meet the specific coverage criteria listed for CD33+ acute myeloid leukemia (AML) or the acute promyelocytic leukemia (APL) indications (NCCN 2A) described in this policy. Specifically, requests that do not satisfy the required diagnosis, treatment setting (induction, consolidation, or relapsed/refractory for AML), or the APL-specific criteria (including the white blood cell thresholds of > 10,000/mcL for high-risk and ≤ 10,000/mcL for low-risk when arsenic is unavailable or contraindicated, relapsed disease, or leukocytosis associated with differentiation syndrome used as a single agent) are not eligible for approval, as are requests for any other, non-listed indications.

Study	Setting / Regimen	Key finding / relevance
ALFA-0701	Gemtuzumab ozogamicin added to standard induction chemotherapy for newly diagnosed AML (younger adults)	Demonstrated benefit in event-free survival when added to standard induction/consolidation regimens; supports use of Mylotarg in combination with induction/consolidation chemotherapy in selected AML patients.
Castaigne et al. (2012)	Gemtuzumab ozogamicin combined with conventional induction and consolidation regimens in newly diagnosed AML	Reported improved outcomes (event-free survival/overall survival or durable complete remission) leading to re-approval and supporting addition to standard regimens in selected patients.
Meta-analyses (referenced)	Pooled analyses of randomized trials evaluating addition of gemtuzumab ozogamicin to induction/consolidation chemotherapy	Overall trial data support benefit in specific populations, informing coverage of gemtuzumab added to induction or consolidation regimens.

Recommendation source	APL setting / regimen	Coverage implication
NCCN (category 2A) and referenced APL literature	Gemtuzumab ozogamicin as single agent or in combination with APL regimens for: high-risk APL (WBC > 10,000/mcL); low-risk APL when arsenic trioxide is unavailable or contraindicated; relapsed APL; leukocytosis associated with APL differentiation syndrome (single-agent use)	Supports coverage of gemtuzumab ozogamicin for specified APL indications per NCCN 2A guidance.
Abaza et al. (2017)	ATRA + arsenic trioxide + gemtuzumab in APL regimens (reported in referenced literature)	Clinical series supporting inclusion of gemtuzumab in APL therapeutic approaches; cited in NCCN guidance and referenced in policy.

Coding

HCPCSHCPCS

J9203

Injection, gemtuzumab ozogamicin, 0.1 mg [Mylotarg]

ICD-10 DiagnosisICD-10

C92.00-C92.02	Acute myeloblastic leukemia
C92.40-C92.42	Acute promyelocytic leukemia
C92.50-C92.52	Acute myelomonocytic leukemia
C92.60-C92.62	Acute myeloid leukemia with 11q23-abnormality
C92.A0-C92.A2	Acute myeloid leukemia with multilineage dysplasia
C93.00-C93.02	Acute monoblastic/monocytic leukemia
C94.00-C94.02	Acute erythroid leukemia
C94.20-C94.22	Acute megakaryoblastic leukemia

White blood cell count — APL risk thresholds

High-risk APL thresholdWhite blood cell count > 10,000/mcL defines high-risk APL

Low-risk APL thresholdWhite blood cell count ≤ 10,000/mcL defines low-risk APL

Action for low-risk when arsenic unavailableLow-risk APL (WBC ≤ 10,000/mcL) may be eligible when arsenic is not available or is contraindicated

Provider Actions and Documentation

Prior Authorization

Prior Authorization Required

Prior authorization is required for requests for Mylotarg (gemtuzumab ozogamicin). Requests will be reviewed against clinical criteria specifying diagnosis and treatment setting (CD33+ AML used as induction, consolidation, or for relapsed/refractory disease; or APL per NCCN 2A with specified high‑risk/low‑risk/relapsed/differentiation‑syndrome conditions).

Prior authorization required and clinical review for diagnosis: CD33+ AML or APL (NCCN 2A).
Approved treatment settings for CD33+ AML: induction, consolidation, or treatment of relapsed/refractory disease.
Approved APL situations: high‑risk disease (WBC > 10,000/mcL); low‑risk (WBC ≤ 10,000/mcL) when arsenic is unavailable or contraindicated; relapsed disease; leukocytosis with APL differentiation syndrome when used as a single agent.

Documentation Required

Include documentation to support the diagnosis, indication, and the specific clinical scenario used to meet medical necessity. Provide relevant clinical notes, laboratory values (e.g., WBC count to document high‑risk vs low‑risk APL), prior treatment history, and rationale when arsenic is unavailable or contraindicated. Coding is provided for informational purposes only and does not determine coverage.

Document diagnosis: CD33+ AML or APL (note NCCN 2A for APL).
Provide WBC count when claiming APL high‑risk (> 10,000/mcL) or low‑risk (≤ 10,000/mcL).
Include prior treatment history and reasons arsenic is unavailable/contraindicated when applicable.
Attach supporting clinical notes and any relevant lab/imaging reports.

Denial Risk

Denial Triggers

Requests may be denied if the patient does not meet the listed criteria (e.g., not CD33+ AML or not meeting an approved AML treatment setting; or APL that does not meet NCCN 2A and the specified APL conditions). Requests may also be denied for all other indications not listed in the clinical criteria.

Denial likely if diagnosis is not CD33+ AML or APL per NCCN 2A.
Denial likely if CD33+ AML use is not for induction, consolidation, or relapsed/refractory treatment.
Denial likely if APL cases do not meet the high‑risk/low‑risk/relapsed/differentiation‑syndrome criteria.
Requests for indications other than those specified may not be approved.

Covered Regimens and Regimen-Level Evidence

Study	Setting / Regimen	Key finding / relevance
ALFA-0701	Addition of gemtuzumab ozogamicin to standard induction chemotherapy in newly diagnosed AML	Trial evidence demonstrating benefit in event-free survival supporting addition to induction/consolidation regimens for selected patients.
Castaigne et al. (2012) and other supportive trials	Gemtuzumab ozogamicin combined with conventional induction and consolidation regimens	Provided evidence of improved outcomes (event-free survival/overall survival or durable remission) that informed re-approval and coverage of combination use.
Meta-analyses (referenced)	Pooled analyses of trials of gemtuzumab added to induction/consolidation chemotherapy	Aggregate data support benefit in specific populations, underpinning coverage for combination regimens.

Recommendation source	APL setting / regimen	Coverage implication
NCCN (category 2A) and referenced APL literature	Use of gemtuzumab ozogamicin as single agent or in combination with APL regimens for: high-risk APL (WBC > 10,000/mcL); low-risk APL when arsenic trioxide is unavailable or contraindicated; relapsed APL; leukocytosis associated with APL differentiation syndrome (single-agent use)	Policy supports coverage for these NCCN-specified APL indications, including single-agent use for leukocytosis associated with differentiation syndrome.
Abaza et al. (2017)	ATRA + arsenic trioxide + gemtuzumab combinations reported in APL literature	Cited clinical reports that bolster NCCN recommendations and the policy's APL coverage statements.

Definitions

APL — definition

DefinitionAcute promyelocytic leukemia (APL): an aggressive subtype of acute myeloid leukemia (AML)

Clinical contextAPL may require risk stratification by white blood cell count for treatment selection

Guideline referenceNCCN category 2A recommendations referenced for APL uses in policy

Refractory Disease — definition

DefinitionRefractory disease: illness or disease that does not respond to treatment

Context of useIncluded as an acceptable treatment setting for Mylotarg in relapsed or refractory AML

DocumentationClinical documentation should show lack of response to prior therapy to support 'refractory' designation

Background

Mylotarg (gemtuzumab ozogamicin) is a CD33-targeting antibody–drug conjugate that delivers the cytotoxic agent calicheamicin to CD33-expressing malignant myeloid cells. It is indicated under this policy for selected patients with CD33+ acute myeloid leukemia (AML) in the settings of induction, consolidation, or relapsed/refractory disease, and for specified uses in acute promyelocytic leukemia (APL) consistent with NCCN category 2A recommendations (including high-risk APL with WBC > 10,000/mcL, certain low‑risk scenarios when arsenic is unavailable or contraindicated, relapsed APL, and as a single agent for leukocytosis associated with APL differentiation syndrome). The agent carries important safety considerations (including boxed warnings for hepatotoxicity/veno‑occlusive disease) and should be used in accordance with the clinical criteria outlined in this policy.

Revision History

2025-02-21Annual review (material)Latest

Annual review added an APL indication: included use for leukocytosis associated with APL differentiation syndrome as a single agent (APL NCCN criteria updated).

2024-02-23Annual review

Updated APL criteria to include low-risk and relapsed disease per NCCN guidance.

2023-02-24Annual review

Clarified use in newly diagnosed AML as induction or consolidation therapy and removed requirement for ineligible for anthracycline for APL.

2020-08-21Select review

Removed age from criteria during a select review.

2019-05-17Annual review (first review)

First review of Mylotarg clinical criteria with minor wording and formatting updates and addition of a reference for off-label criteria.

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