CurrentPremera BluecrossPolicy N/A

Antibody-Drug Conjugates

Medical policy specifying medical necessity criteria, age considerations, authorization lengths, coding, and investigational exclusions for multiple FDA-labeled antibody-drug conjugates (listed drugs) managed under the medical benefit.

Policy Summary

PayerPremera Bluecross

PolicyAntibody-Drug Conjugates

Policy CodePolicy N/A

Change TypeMultiple additions and revisions (Datroway addedPadcev broadenedBesponsa pediatric age updatedcoding/HCPCS updates).

Effective DateFeb 1, 2026

Next Review DateN/A

Key ActionEvaluate ADC requests against the policy's FDA-aligned medical necessity criteria and submit prior authorization with documentation of indication, FDA dosing, age where relevant, and applicable HCPCS codes; non-formulary exceptions may be approved up to 12 months.

SourceLink

POLICY UPDATE CHANGES

Added coverage criteria for Datroway (datopotamab deruxtecan-dlnk).

Updated Padcev coverage criteria to include combination with pembrolizumab and berahyaluronidase alfa (and for neoadjuvant/adjuvant MIBC usage).

Updated Besponsa (inotuzumab ozogamicin) age requirement from 18 to 1 year of age or older.

Clarified non-formulary exception review authorizations may be approved up to 12 months and that medications are subject to the product's FDA dosing.

Added Elahere coverage for FRα positive platinum-resistant ovarian/fallopian/primary peritoneal cancer after 1–3 prior regimens.

Added Zynlonta criteria for relapsed/refractory large B-cell lymphoma after ≥2 prior systemic therapies.

11Drugs with specific coverage criteria listed

9ADC agents referenced/covered (approx.)

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12HCPCS/J codes listed

>=12HCPCS/Coding changes tracked

12Max non-formulary exception duration (months)

1Investigational category (all other uses)

Coverage Summary

This policy covers FDA-labeled antibody-drug conjugates (ADCs) that are managed under the medical benefit, outlining medical necessity criteria, age considerations, authorization lengths, coding, and investigational exclusions; effective Feb. 1, 2026, last reviewed Jan. 13, 2026. Coverage stance is mixed and the policy includes specific criteria for 11 drugs with listed coverage criteria and 12 HCPCS/J codes tracked in the document.

Quick Reference — Key Thresholds & Administrative Items

c-Met overexpression threshold>=50% of tumor cells with strong (3+) IHC staining

Datroway age requirement>=18 years

Adcetris pediatric lower age>=2 years (and <22 years for specified high‑risk pediatric cHL)

Max non‑formulary exception authorization durationUp to 12 months for initial non‑formulary exception reviews

Policy‑managed benefitDrugs in this policy are managed through the medical benefit (administered and billed under medical benefit)

Medical Necessity Criteria

Adcetris (brentuximab vedotin) - Medical Necessity

Adcetris (brentuximab vedotin) may be considered medically necessary for the labeled indications below. Pediatric age note: where pediatric age ranges are specified, those age thresholds apply.

ALL of the following

Previously untreated Stage III or IV classical Hodgkin lymphoma (cHL), in combination with chemotherapy.
Pediatric individuals aged 2 years to less than 22 years with previously untreated high risk (Ann Arbor Stage IIB with bulk disease, Stage IIIB, Stage IVA, and Stage IVB) classical Hodgkin lymphoma (cHL), in combination with doxorubicin, vincristine, etoposide, prednisone, and cyclophosphamide (AVE-PC).
Pediatric age-specific regimen
Classical Hodgkin lymphoma at high risk of relapse or progression as post-autologous hematopoietic stem cell transplantation (auto-HSCT) consolidation.

Coding

HCPCS / J-codes listedHCPCS

C9174	Injection, datopotamab deruxtecan-dlnk (Datroway), 1 mg (new code effective 07/01/25) (code termed 10/01/25)
C9306	Injection, telisotuzumab vedotin-tllv (Emrelis), 1 mg (code termed 01/01/26)
J9011	Injection, datopotamab deruxtecan-dlnk (Datroway), 1 mg (new code effective 10/01/25)
J9042	Injection, brentuximab vedotin (Adcetris), 1 mg
J9063	Injection, mirvetuximab soravtansine-gynx (Elahere), 1 mg
J9177	Injection, enfortumab vedotin-ejfv (Padcev), 0.25 mg
J9203	Injection, gemtuzumab ozogamicin (Mylotarg), 0.1 mg
J9229	Injection, inotuzumab ozogamicin (Besponsa), 0.1 mg
J9273	Injection, tisotumab vedotin-tftv (Tivdak), 1 mg
J9309	Injection, polatuzumab vedotin-piiq (Polivy), 1 mg

1–10 of 12

1/2

HCPCS codes added/associated (policy history lists many code changes)HCPCS

J9229	Added effective 1/1/19 (coding update referenced)
J9177	Added 04/01/22
C9084	Added 10/01/21; later removed 04/01/23
J3590	Added 06/01/21; removed and later re-added for Emrelis then removed again per history
C9146	Added 04/01/23; removed 07/01/23
J9063	Added 07/01/23
J9042	Added for Adcetris (history 07/01/25)
J9309	Added for Polivy (history 07/01/25)
C9174	Added then removed (10/01/25 removed)
C9306	Added 10/01/25 then termed effective 01/01/26 per history

1–10 of 12

1/2

Provider Actions / Billing & Authorization

Prior Authorization

Authorization lengths and requirements

Initial non-formulary exception authorizations for specified ADCs may be approved for up to 12 months. Re-authorization requirements vary by drug and generally require documentation of continued positive clinical response and adherence to drug-specific coverage criteria. Besponsa and Mylotarg have distinct shorter initial/other review limits (may be approved up to 3 months for some reviews) and specific re-authorization rules.

Besponsa and Mylotarg: some reviews may be approved up to 3 months; re-authorization for Besponsa and Mylotarg may be approved up to 12 months if drug-specific criteria are met and chart notes document continued positive clinical response.
Other listed ADCs (Adcetris, Datroway, Elahere, Emrelis, Padcev, Tivdak, Zynlonta): non-formulary exception reviews may be approved up to 12 months; other reviews may be approved up to 6 months as specified.

Prior Authorization

Prior authorization required per medical policy

Medications in this policy require evaluation against the medical policy for medical necessity prior to coverage. Non-formulary exception authorizations for the drugs listed may be approved for up to 12 months.

Background & Evidence

Antibody-drug conjugates (ADCs) combine a monoclonal antibody targeted to tumor-cell antigens with a cytotoxic payload and a linker so the antibody directs delivery of chemotherapy directly into cancer cells, aiming to spare healthy tissues. The policy summarizes FDA-labeled indications for multiple ADC agents (examples include Adcetris, Besponsa, Datroway, Elahere, Emrelis, Mylotarg, Padcev, Polivy, Tivdak, and Zynlonta) and provides clinical trial evidence summaries for many listed agents to support the coverage positions without reproducing full trial data here.

Study / Endpoint	Key result
Adcetris (Study 3) - post-auto‑HSCT consolidation PFS	Statistically significant improvement in IRF‑assessed progression‑free survival vs placebo; increase in median PFS (randomized placebo‑controlled trial)
Besponsa (INO‑VATE ALL) - CR/CRi	CR/CRi 80.7% vs 29.4% for standard chemotherapy in randomized subset
Datroway (TROPION‑Breast01) - PFS/ORR	Median PFS 6.9 vs 4.9 months vs chemotherapy; ORR 36% vs 23% (median DOR 6.7 vs 5.7 months)
Zynlonta (LOTIS‑2) - ORR/DOR	ORR 48.3% (95% CI 39.9%–56.7%); median duration of response 10.3 months
Tivdak (innovaTV204) - ORR/DOR	ORR 24% (95% CI 15.9%–33.3%); median duration of response 8.3 months
Polatuzumab + R/G‑CHP (Phase Ib/II) - frontline DLBCL	ORR 89% (59/66) with 77% CR; 12‑month PFS 91%, 24‑month PFS 83%
Besponsa safety (INO‑VATE ALL) - hepatotoxicity/VOD	14% hepatotoxicity/VOD observed; VOD reported up to 56 days post last dose; fatal VOD cases reported

Definitions

auto-HSCT: Autologous hematopoietic stem cell transplantation

ADC: Antibody-drug conjugate

IHC: Immunohistochemistry

ADC: Antibody-drug conjugate.

FDA prescribing information: Official product labeling that includes approved indications, dosing, and safety information.

Revision History

06/01/21Added

Added Zynlonta criteria for relapsed/refractory large B-cell lymphoma after ≥2 prior systemic therapies.

01/01/23Added

Added Elahere coverage for FRα positive platinum-resistant ovarian/fallopian/primary peritoneal cancer after 1–3 prior regimens.

06/01/23Revised

Updated Padcev coverage criteria to include use in combination with pembrolizumab for treatment of adult individuals with locally advanced or metastatic urothelial cancer (not eligible for cisplatin-containing chemotherapy).

Policy Summary

PayerPremera Bluecross

PolicyAntibody-Drug Conjugates

Policy CodePolicy N/A

Change TypeMultiple additions and revisions (Datroway addedPadcev broadenedBesponsa pediatric age updatedcoding/HCPCS updates).

Effective DateFeb 1, 2026

Next Review DateN/A

SourceLink

On This Page

Classical Hodgkin lymphoma after failure of auto-HSCT or after failure of at least two prior multi-agent chemotherapy regimens in individuals who are not auto-HSCT candidates.

Previously untreated systemic anaplastic large cell lymphoma (sALCL) or other CD30-expressing peripheral T-cell lymphomas (PTCL), including angioimmunoblastic T-cell lymphoma and PTCL not otherwise specified, in combination with chemotherapy.

Systemic anaplastic large cell lymphoma (sALCL) after failure of at least one prior multi-agent chemotherapy regimen.

Primary cutaneous anaplastic large cell lymphoma (pcALCL) or CD30-expressing mycosis fungoides (MF) who have received prior systemic therapy.

Besponsa (inotuzumab ozogamicin) - Medical Necessity

Besponsa (inotuzumab ozogamicin) may be considered medically necessary when the following age and clinical criteria are met.

ALL of the following

The individual is aged 1 year or older.
Clinical indication consistent with the product labeling (e.g., appropriate B-cell precursor acute lymphoblastic leukemia scenarios per FDA approval).

Datroway (datopotamab deruxtecan-dlnk) - Medical Necessity

Datroway (datopotamab deruxtecan-dlnk) may be considered medically necessary for the labeled breast cancer and NSCLC indications when prescribed by or in consultation with an oncologist.

ANY of the following

Breast cancer indication
- The individual is aged 18 years or older.
- Has been diagnosed with unresectable or metastatic, hormone receptor (HR)-positive, HER2-negative (IHC 0, IHC 1+, or IHC 2+/ISH-) breast cancer.
- Has received prior endocrine-based therapy and chemotherapy for unresectable or metastatic disease.
- Prescribed by or in consultation with an oncologist.
NSCLC indication
- The individual is aged 18 years or older.
- Has been diagnosed with locally advanced or metastatic EGFR-mutated non-small cell lung cancer (NSCLC).
- Has received prior EGFR-directed therapy (e.g., afatinib, gefitinib, osimertinib) and platinum-based chemotherapy (e.g., cisplatin, carboplatin, oxaliplatin).
- Prescribed by or in consultation with an oncologist.

Elahere (mirvetuximab soravtansine-gynx) - Medical Necessity

Elahere (mirvetuximab soravtansine-gynx) may be considered medically necessary for labeled FRα-positive, platinum-resistant epithelial ovarian, fallopian tube, or primary peritoneal cancer.

ALL of the following

The individual is aged 18 years or older.
Has been diagnosed with folate receptor alpha (FRα)–positive, platinum-resistant epithelial ovarian, fallopian tube, or primary peritoneal cancer.

Emrelis (telisotuzumab vedotin-tllv) - Medical Necessity

Emrelis (telisotuzumab vedotin-tllv) may be considered medically necessary when c-Met overexpression and line-of-therapy criteria are met.

ALL of the following

The individual is aged 18 years or older.
Has been diagnosed with locally advanced or metastatic non-squamous non–small cell lung cancer (NSCLC).
Tumor demonstrates high c-Met protein overexpression defined as ≥50% of tumor cells with strong (3+) IHC staining.>= 50%
Has received 1 or more lines of systemic therapy.

Mylotarg (gemtuzumab ozogamicin) - Medical Necessity

Mylotarg (gemtuzumab ozogamicin) may be considered medically necessary for CD33-positive acute myeloid leukemia with pediatric age thresholds that differ for newly diagnosed versus relapsed/refractory disease.

ANY of the following

Newly diagnosed AML
- Newly-diagnosed CD33-positive Acute Myeloid Leukemia (AML).
- Individual is an adult or a pediatric individual aged 1 month and older.
Relapsed or refractory AML
- Relapsed or refractory CD33-positive AML.
- Individual is an adult or a pediatric individual aged 2 years and older.

Padcev (enfortumab vedotin) - Medical Necessity

Padcev (enfortumab vedotin-ejfv) may be considered medically necessary for muscle invasive bladder cancer (MIBC) in the perioperative setting in combination with pembrolizumab ± berahyaluronidase alfa per criteria, and for locally advanced/metastatic urothelial cancer as single-agent or in combination per the branches below.

ANY of the following

MIBC neoadjuvant/adjuvant combination
- The individual is aged 18 years or older.
- Is ineligible for cisplatin-containing chemotherapy.
- Padcev is used in combination with pembrolizumab or pembrolizumab and berahyaluronidase alfa-pmph as neoadjuvant treatment and then continued after cystectomy as adjuvant treatment.
Locally advanced or metastatic urothelial cancer (mUC)
- The individual is aged 18 years or older.
- As a single agent: individual is ineligible for cisplatin-containing chemotherapy and has previously received 1 or more prior lines of therapy, OR individual has previously received a PD-1/PD-L1 inhibitor and a platinum-containing chemotherapy.
- In combination: used with pembrolizumab or pembrolizumab and berahyaluronidase alfa per labeled combinations.

Polivy (polatuzumab vedotin-piiq) - Medical Necessity

Polivy (polatuzumab vedotin-piiq) may be considered medically necessary for frontline and relapsed/refractory large B-cell lymphoma indications as specified below.

ANY of the following

Frontline DLBCL / HGBL with R-CHP
- In combination with a rituximab product, cyclophosphamide, doxorubicin, and prednisone (R-CHP) for adult individuals who have previously untreated diffuse large B-cell lymphoma (DLBCL) NOS or high-grade B-cell lymphoma (HGBL).
- Individual has an International Prognostic Index (IPI) score of 2 or greater.
Relapsed/refractory DLBCL or bridging prior to CAR-T
- In combination with bendamustine and a rituximab product for adult individuals with relapsed or refractory DLBCL NOS.
- Or used as bridging therapy prior to an anti-CD19 CAR-T therapy.

Tivdak (tisotumab vedotin-tftv) - Medical Necessity

Tivdak (tisotumab vedotin-tftv) may be considered medically necessary for recurrent or metastatic cervical cancer after progression on or after chemotherapy.

ALL of the following

The individual is aged 18 years or older.
Has a diagnosis of recurrent or metastatic cervical cancer.
Has had disease progression on or after chemotherapy.

Zynlonta (loncastuximab tesirine-lpyl) - Medical Necessity

Zynlonta (loncastuximab tesirine-lpyl) may be considered medically necessary for relapsed or refractory large B-cell lymphoma after two or more prior systemic therapies.

ALL of the following

The individual is aged 18 years or older.
Has a diagnosis of relapsed or refractory large B-cell lymphoma, including DLBCL NOS, DLBCL arising from low-grade lymphoma, and high-grade B-cell lymphoma.
Has received 2 or more lines of systemic therapy.

Investigational / Not Medically Necessary

Investigational / Not Medically Necessary: all other uses of the medications listed in this policy that are not explicitly included in the medical necessity criteria below are considered investigational and not medically necessary.

ALL of the following

Requests for indications, populations, combinations, dosing, or durations not specified in the labeled medical necessity sections of this policy.
Use of the listed antibody-drug conjugates outside of FDA-approved indications or inconsistent with FDA dosing and pediatric age rules.

Covered Indications (examples from document updates)

Covered Indications (examples from document updates): coverage is provided when the drug is used for an FDA-approved indication listed in this policy and administered per FDA dosing and pediatric age rules. Providers must document indication, prior therapies, and any diagnostic testing (e.g., IHC) required by the specific drug criteria.

ALL of the following

Drug is used for an FDA-approved indication that is explicitly listed in this policy.
Administration and dosing are consistent with the product's FDA prescribing information, including pediatric age thresholds where specified.
Required diagnostic criteria (e.g., biomarker IHC thresholds) and prior therapy requirements documented in the medical record.

Non-covered / Investigational

Non-covered / Investigational: uses outside the policy criteria or inconsistent with required dosing, age, biomarker, or prior therapy rules are non-covered and considered investigational.

ANY of the following

Uses not meeting the drug-specific medical necessity criteria in this policy.
Dosing or duration inconsistent with FDA-approved prescribing information or this policy's specified limits.
Use in populations below the policy-specified pediatric age thresholds.

Documentation Required

Prescriber specialty

Some agents must be prescribed by or in consultation with an oncologist. Datroway’s breast cancer indication specifically requires the drug be prescribed by or in consultation with an oncologist.

Datroway: prescribed by or in consultation with an oncologist is required for the breast cancer indication.

Documentation Required

Documentation must support FDA indication and dosing

Providers must document that the requested medication is being used for an FDA-approved indication and that dosing and administration follow the product’s FDA prescribing information. Documentation should include the indication, dose, schedule, and patient age where relevant (for example, Mylotarg requires age ≥1 month for newly diagnosed CD33+ AML).

Document FDA-approved indication and confirm dosing/administration per FDA prescribing information.
Include patient age when relevant (e.g., Mylotarg: newly diagnosed CD33+ AML in individuals aged 1 month and older).

Billing Rule

Medical benefit management

The antibody‑drug conjugates listed in this policy are managed under the medical benefit and are administered and billed through the medical benefit.

Billing Rule

Use updated HCPCS codes effective dates

Submit claims using the HCPCS/J codes listed in the policy and follow the effective and term dates in the policy history. Use the code that corresponds to the drug and the date of service per the policy coding history.

J9229 (inotuzumab ozogamicin, Besponsa)
J9177 (enfortumab vedotin-ejfv, Padcev)
J9203 (gemtuzumab ozogamicin, Mylotarg)
J9042 (brentuximab vedotin, Adcetris)
J9063 (mirvetuximab soravtansine-gynx, Elahere)
J9309 (polatuzumab vedotin-piiq, Polivy)
J9273 (tisotumab vedotin-tftv, Tivdak)
J9359 (loncastuximab tesirine-lpyl, Zynlonta)
C9174 / J9011 / other Datroway codes per history (C9174 added then termed; J9011/C9174/J9011 coding updates)
C9306 / J9326 / J9011 (telisotuzumab vedotin-tllv / Emrelis coding changes)

Denial Risk

Claims may be denied if criteria not met

Claims may be denied if the use is outside FDA‑approved indications or the specific policy criteria, or if dosing/administration does not follow the FDA prescribing information.

04/01/24Revised

Updated Padcev coverage to include combination with pembrolizumab regardless of cisplatin eligibility.

08/01/24Revised

Updated Besponsa (inotuzumab ozogamicin) age requirement from 18 to 1 year of age or older.

07/01/25Clarified

Clarified non-formulary exception review authorizations may be approved up to 12 months and that medications are subject to the product's FDA dosing and administration prescribing information.

07/01/25Added

Added coverage criteria for Datroway (datopotamab deruxtecan-dlnk); moved Adcetris and Polivy from monoclonal antibody policy into this ADC policy; added HCPCS codes J9042 (Adcetris), J9309 (Polivy) and C9174 (Datroway).

08/01/25Added

Added coverage criteria for Emrelis (telisotuzumab vedotin-tllv) for locally advanced or metastatic non-squamous NSCLC with high c-Met overexpression; added HCPCS J3590 for Emrelis.

09/01/25Revised

Added new Datroway indication for locally advanced or metastatic EGFR-mutated NSCLC.

10/01/25Revised

Coding update: added HCPCS codes C9306 and J9011; removed termed HCPCS code C9174 (effective October 1, 2025).

01/01/26Revised

Coding update: added HCPCS code J9326 and indicated C9306 is termed (effective January 1, 2026).

02/01/26RevisedLatest

Updated Padcev coverage to include combination with pembrolizumab and berahyaluronidase alfa-pmph; added use as neoadjuvant then continued adjuvant treatment for MIBC in patients ineligible for cisplatin-containing chemotherapy.