CurrentAnthemPolicy CC-0088

Medical Drug Clinical Criteria

Medical benefit clinical criteria for the use of Elzonris (tagraxofusp-erzs) in members 2 years of age and older with blastic plasmacytoid dendritic cell neoplasm (BPDCN), including indications, baseline requirements, monitoring guidance, and applicable HCPCS and ICD-10 codes.

Policy Summary

PayerAnthem

PolicyMedical Drug Clinical Criteria

Policy CodePolicy CC-0088

Change TypeCriteria update (NCCN 2A); coding specificity

Effective DateApr 1, 2025

Next Review Date

Key ActionSubmit prior authorization demonstrating patient is >=2 years with BPDCN, intended NCCN 2A place in therapy, monotherapy use, and baseline serum albumin >= 3.2 g/dL.

POLICY UPDATE CHANGES

02/21/2025 - Annual Review: No changes. Coding Reviewed: Further specified ICD-10-CM C86.4 to C86.40 and updated description.

02/23/2024 - Annual Review: Update criteria with 2A recommendations from NCCN for place in therapy. Remove criteria for ECOG score.

02/21/2020 - Annual Review: Update clinical criteria for Elzonris with NCCN AML guideline update and may not be approved criteria. Coding Reviewed: Added ICD-10 Z51.11.

1Covered Indication (BPDCN)

>=2Minimum age

3.2 g/dLBaseline albumin threshold

J9269Primary HCPCS code

Coverage Summary

Scope: Medical benefit clinical criteria for the use of Elzonris (tagraxofusp-erzs) in members 2 years of age and older with blastic plasmacytoid dendritic cell neoplasm (BPDCN), including indications, baseline requirements, monitoring guidance, and applicable HCPCS and ICD-10 codes. Policy number: CC-0088; Effective: 2025-04-01; Status: CURRENT.

Background: Elzonris (tagraxofusp-erzs) is a CD123-directed cytotoxin — a fusion protein of recombinant human interleukin-3 (IL-3) linked to a truncated diphtheria toxin that inhibits protein synthesis and causes cell death in CD123-expressing cells — indicated for blastic plasmacytoid dendritic cell neoplasm (BPDCN), a rare aggressive malignancy that may present with skin lesions, involve lymph nodes and marrow, and often presents as or evolves into acute leukemia. Elzonris carries a black box warning for Capillary Leak Syndrome (CLS); clinical trial data report an overall CLS incidence of 53% (Grade 1–2: 43%; Grade 3: 7%; Grade 4: 1% and 4 fatal events), with common associated findings including hepatotoxicity, hypoalbuminemia, edema, weight gain, and hypotension.

Initial Therapy Criteria

Approval Criteria for Elzonris (tagraxofusp-erzs)

Requests for Elzonris (tagraxofusp-erzs) may be approved if the following criteria are met:

ALL of the following

Age: Individual is 2 years of age or older
Diagnosis: Individual has a diagnosis of blastic plasmacytoid dendritic cell neoplasm (BPDCN)
Place in therapy (NCCN 2A)
- Induction: For intensive remission induction therapy
- Maintenance: Treatment until progression if complete response (CR) achieved after induction
- Relapsed/Refractory: Relapsed/refractory disease, if not already used
Monotherapy: Individual is using Elzonris as monotherapy
Baseline serum albumin: At initial therapy, individual has a baseline serum albumin of 3.2 g/dL or higher>= 3.2 g/dL
Monitor serum albumin prior to each dose and assess for signs/symptoms of Capillary Leak Syndrome (CLS)

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Continuation Criteria & Denial Conditions

Denial Conditions

Requests may not be approved when the above criteria are not met and for all other indications.

Missing approval criterion: Any criterion in the approval criteria is not met
Unlisted indication: Use for indications other than BPDCN or uses not listed in approval criteria

Prior Authorization

Prior authorization required per clinical criteria

Submit prior authorization requests demonstrating patient age >= 2 years, diagnosis of blastic plasmacytoid dendritic cell neoplasm (BPDCN), intended place in therapy per NCCN 2A (induction, treatment until progression if CR, or relapsed/refractory if not previously used), monotherapy use, and baseline serum albumin >= 3.2 g/dL. Include applicable drug HCPCS code J9269.

Applicable Codes

Drug HCPCSHCPCSCovered

J9269

Injection, tagraxofusp-erzs, 10 micrograms [Elzonris]

Relevant ICD-10 Diagnosis Codes (informational)ICD-10

C86.40	Blastic NK-cell lymphoma not having achieved remission
Z51.11	Encounter for antineoplastic chemotherapy

Clinical Evidence & Safety

2ANCCN recommendation: single-agent for induction; maintenance until progression if CR; or relapsed/refractory

53%Overall CLS incidence in trials (Grade1-2:43%; Grade3:7%; Grade4:1%; 4 fatal events)

Capillary Leak Syndrome (CLS) is defined here as a severe adverse event characterized by increased vascular permeability leading to hypoalbuminemia, edema, hypotension, and potential multi-organ dysfunction; Elzonris carries a black box warning for CLS and clinical trial experience showed substantial incidence and serious outcomes. Because of this risk, baseline and ongoing monitoring is required: ensure baseline serum albumin is >= 3.2 g/dL prior to initiation, assess baseline cardiac function, monitor serum albumin prior to each dose, and evaluate for signs and symptoms of CLS during treatment (weight gain, new or worsening edema including pulmonary edema, hypotension or hemodynamic instability). The National Comprehensive Cancer Network (NCCN) provides a Category 2A place-in-therapy recommendation for Elzonris as a single agent for induction in candidates for intensive remission therapy, for treatment until progression if a complete response is achieved after induction, or for relapsed/refractory disease (if not already used), which informs appropriate use despite the CLS risk.

Background & Definitions

Elzonris is a CD123-directed cytotoxin composed of recombinant human IL-3 fused to a truncated diphtheria toxin that inhibits protein synthesis in CD123-expressing cells. It is indicated for BPDCN, a rare aggressive neoplasm that can involve skin, lymph nodes and bone marrow and often presents as or progresses to acute leukemia. Elzonris carries a black box warning for Capillary Leak Syndrome (CLS); clinical trial rates of CLS were substantial (overall 53%, with Grade 3–4 events and reported fatalities), and baseline serum albumin < 3.2 g/dL is an exclusion for initiation until corrected per policy guidance.

Term	Definition
ECOG Performance Status	Scale to assess functional status ranging from 0 (fully active) to 5 (dead); previously considered but removed from criteria.
Capillary Leak Syndrome (CLS)	A severe adverse event characterized by increased vascular permeability leading to hypoalbuminemia, edema, hypotension, and potential multi-organ dysfunction.

Revision History

02/21/2020material

Annual Review: Clinical criteria updated per NCCN AML guideline; ICD-10 code Z51.11 (Encounter for antineoplastic chemotherapy) added to coding.

02/23/2024material

Annual Review: Clinical criteria updated to incorporate NCCN Category 2A recommendations for place in therapy (induction, maintenance if CR, or relapsed/refractory) and ECOG performance status removed from criteria.

02/21/2025non-materialLatest

Annual Review: No clinical changes; coding specificity updated by further specifying ICD-10-CM C86.4 to C86.40 with updated description.