CurrentNeighborhood Health Plan of Rhode IslandPolicy N/A

Besponsa (inotuzumab ozogamicin) — coverage criteria

Defines accepted indications, limits, and coding for inotuzumab ozogamicin (Besponsa) use for treatment of acute lymphoblastic leukemia (ALL) and outlines requirements for authorization and evidence sources for Neighborhood Health Plan of Rhode Island members.

Policy Summary

PayerNeighborhood Health Plan of Rhode Island

PolicyBesponsa (inotuzumab ozogamicin) — coverage criteria

Policy CodePolicy N/A

Change TypeIndication updated (pediatric age ≥ 1 year)

Effective DateN/A

Next Review DateN/A

Key ActionObtain prior authorization through Evolent and document CD22 positivity on leukemia cells for coverage.

SourceLink

POLICY UPDATE CHANGES

Indication updated to include use in pediatric members age ≥ 1 year.

Converted to new Evolent guideline template and replaced previous UM ONC_1330 Besponsa policy.

≥1 yrminimum patient age for pediatric indication

0.8 mg/m2single dose maximum

6max treatment cycles (no HSCT)

J9229HCPCS billing code

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Coverage Criteria for Inotuzumab Ozogamicin (Besponsa)

Covered Indications

Covered when ALL of the following are met

Indication: Member has relapsed or refractory B-cell acute lymphoblastic leukemia (ALL) and disease is CD22-positive

Applies to adult and pediatric members age ≥ 1 year; documentation of CD22 positivity required

Disease specifics: Use as a single agent for Philadelphia chromosome negative relapsed/refractory CD22-positive B-cell ALL OR in combination with a tyrosine kinase inhibitor for Philadelphia chromosome positive relapsed/refractory CD22-positive B-cell ALL

Examples of tyrosine kinase inhibitors include imatinib

Requests for Besponsa (inotuzumab ozogamicin) will be denied when used after documented disease progression on the same regimen. Additionally, use for investigational or off‑label indications that lack sufficient evidence or are not generally accepted by the medical community is excluded. The policy defines insufficient evidence as lack of adequate representation of the patient/cancer population in published studies, inadequate representation of the administered regimen, absence of clinically meaningful outcomes (for example, an OS or PFS benefit of at least 3 months or ASCO‑recommended thresholds such as a hazard ratio < 0.80), inappropriate experimental design for the question, reliance solely on uncontrolled case reports, or abstracts without a full peer‑reviewed article.

Dosing that exceeds a single dose of 0.8 mg/m2 is excluded from coverage. In addition, when hematopoietic stem cell transplant (HSCT) is not planned, treatment that exceeds a total of 6 cycles is not covered.

Coverage requires documentation that the member’s leukemia cells are CD22‑positive. Requests lacking documentation of CD22 positivity are not medically necessary and will be excluded. Use of Besponsa for investigational or off‑label indications without sufficient supporting evidence (as defined in the policy) is also not covered.

Covered Regimens and Indications

Regimen	Indication	Coverage status
Inotuzumab ozogamicin as single agent
Philadelphia chromosome negative relapsed/refractory CD22-positive B-cell ALL
Covered (with criteria)

Regimen	Indication	Coverage status
Inotuzumab ozogamicin in combination with a tyrosine kinase inhibitor (e.g., imatinib)
Philadelphia chromosome positive relapsed/refractory CD22-positive B-cell ALL
Covered (with criteria)

Line of Therapy

salvage

Line of therapy: Indicated for relapsed or refractory disease (salvage therapy)

Policy describes use in relapsed/refractory (salvage) settings

Biomarker Requirements

CD22 — Documentation of CD22 positivity on leukemia cells

Required biomarkerDocumentation of CD22 positivity on leukemia cells is required for coverage

Acceptable documentation sourcesPathology or flow cytometry report demonstrating CD22 expression on leukemic blasts

Applies toAdult and pediatric members age ≥ 1 year when meeting covered indications

Coding and Dose Limits

Covered HCPCS CodesHCPCSCovered

J9229

Injection, inotuzumab ozogamicin, 0.1 mg

Single dose maximum — 0.8 mg/m2

Single dose maximum0.8 mg/m2 per administration

Related codingEnsure per-dose calculation does not exceed threshold when billing J9229 (0.1 mg units)

Denial riskRequests exceeding 0.8 mg/m2 may be denied per exclusion criteria

Maximum treatment cycles (if HSCT not planned) — 6 cycles

Maximum treatment cyclesUp to 6 total cycles when hematopoietic stem cell transplant (HSCT) is not planned

HSCT considerationIf HSCT is planned, different limits and risks (e.g., VOD) apply and should be managed clinically

Provider Actions, Authorization, and Documentation

Prior Authorization

Prior Authorization Required

Prior authorization is required for Besponsa (inotuzumab ozogamicin). Evolent is responsible for processing all medication requests from network ordering providers; medications not authorized by Evolent may be deemed not approvable and not reimbursable.

Prior authorization and processing: Evolent handles all medication requests for network providers.
Billing code: J9229 - Injection, inotuzumab ozogamicin, 0.1 mg.

Documentation Required

Required Supporting Documentation

Provide documentation demonstrating the medical necessity and accepted indication for Besponsa. Acceptable evidence sources include FDA-approved product labeling, CMS-recognized compendia, NCCN or ASCO clinical guidelines, or peer-reviewed literature meeting CMS Medicare Benefit Policy Manual Chapter 15 standards.

Acceptable evidence: FDA labeling; CMS-approved compendia; NCCN or ASCO clinical guidelines; peer-reviewed literature that satisfies CMS Medicare Benefit Policy Manual Chapter 15.

Key Definitions

CD22-positive B cell ALL — definition and documentation requirement

DefinitionAcute lymphoblastic leukemia (ALL) with leukemic blasts expressing the CD22 antigen (CD22-positive B cell ALL)

Documentation requirementPathology or flow cytometry confirming CD22 expression on leukemia cells is required for coverage

Covered settingsApplies to relapsed or refractory B-cell ALL as described in the covered indications (single agent or with a TKI)

Veno-occlusive disease (VOD) — definition and clinical relevance related to inotuzumab ozogamicin

DefinitionVeno-occlusive disease (VOD) is hepatotoxicity that can be fatal or life-threatening and has been reported with inotuzumab ozogamicin

Clinical relevanceRisk of VOD is increased in patients who undergo HSCT after inotuzumab ozogamicin, especially with conditioning regimens containing two alkylating agents or pre-HSCT bilirubin ≥ ULN

Background

Inotuzumab ozogamicin (Besponsa) is an anti‑CD22 antibody–drug conjugate used for relapsed or refractory B‑cell acute lymphoblastic leukemia. Its use carries a boxed warning for hepatotoxicity, including veno‑occlusive disease (VOD), with increased risk when followed by HSCT or with certain conditioning regimens.

Revision History and Policy Changes

2025-04operationalLatest

Converted to the new Evolent guideline template and replaced prior policy UM ONC_1330 (Besponsa).

2024-04clinical_indication_update

Indication updated to explicitly include use in pediatric members age ≥ 1 year.