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CurrentPremera BluecrossPolicy 5.01.582

Antibody-Drug Conjugates

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Defines medical necessity, coverage criteria, authorization lengths, documentation, and coding for specific antibody-drug conjugate therapies managed under the medical benefit for Premera Blue Cross members.

Policy Summary

PayerPremera Bluecross

PolicyAntibody-Drug Conjugates

Policy CodePolicy 5.01.582

Change TypeAnnual review (no material changes)

Effective DateAug 1, 2026

Last ReviewJul 14, 2026

Next Review DateAug 1, 2026

Key ActionSubmit prior authorization with documentation of indication, prior therapies, ECOG status, and required biomarker test results.

SourceLink

POLICY UPDATE CHANGES

No material clinical or coverage changes in this revision.

>= 12ADC products with specific coverage language in this part of the policy

3 moInitial approval length (example)

6-12 moRe-authorization approval lengths

MedicalBenefit application

12 moClarified non-formulary exception duration

Coverage Criteria for ADCs

Drug-specific labeled indications

Covered when the drug-specific labeled indications and listed conditions are met

Adcetris (brentuximab vedotin): May be considered medically necessary for labeled indications including: previously untreated Stage III or IV classical Hodgkin lymphoma in combination with chemotherapy; pediatric individuals aged 2 to <22 years with previously untreated high‑risk classical Hodgkin lymphoma in combination with AVE‑PC; post‑autologous HSCT consolidation for high‑risk classical Hodgkin lymphoma; classical Hodgkin lymphoma after failure of auto‑HSCT or after ≥2 prior multi‑agent regimens in non‑auto‑HSCT candidates; previously untreated systemic anaplastic large cell lymphoma (sALCL) or other CD30‑expressing peripheral T‑cell lymphomas in combination with chemotherapy; sALCL after failure of ≥1 prior multi‑agent regimen; primary cutaneous ALCL or CD30‑expressing mycosis fungoides after prior systemic therapy.

Besponsa (inotuzumab ozogamicin): May be considered medically necessary when all criteria are met, including age ≥1 year and diagnosis of relapsed or refractory CD22‑positive B‑cell precursor acute lymphoblastic leukemia (ALL) as defined in the INO‑VATE ALL trial.

Datroway (datopotamab deruxtecan‑dlnk):

Policy Summary

PayerPremera Bluecross

PolicyAntibody-Drug Conjugates

Policy CodePolicy 5.01.582

Change TypeAnnual review (no material changes)

Effective DateAug 1, 2026

Last ReviewJul 14, 2026

Next Review DateAug 1, 2026

Key ActionSubmit prior authorization with documentation of indication, prior therapies, ECOG status, and required biomarker test results.

SourceLink

On This Page

Adcetris coverage criteria

Adcetris (brentuximab vedotin) covered when ALL of the following are met in studied populations:

Adcetris post‑auto‑HSCT consolidation: Classical Hodgkin lymphoma patients at high risk of relapse/progression post‑autologous HSCT (refractory disease, relapse within 12 months, or relapse ≥12 months with extranodal disease); achieved CR, PR, or SD to most recent pre‑auto‑HSCT salvage therapy; treatment per trial dosing (1.8 mg/kg IV every 3 weeks up to 16 cycles).

Adcetris relapsed classical HL after auto‑HSCT: Patients with classical Hodgkin lymphoma who relapsed after autologous HSCT treated per single‑arm trial dosing (1.8 mg/kg IV every 3 weeks).

Adcetris relapsed sALCL: Patients with relapsed systemic anaplastic large cell lymphoma (sALCL) after prior therapy; treatment per single‑arm trial dosing (1.8 mg/kg IV every 3 weeks).

Padcev coverage criteria

Padcev (enfortumab vedotin) covered when matching studied populations and regimens:

Padcev for metastatic urothelial carcinoma after platinum and PD‑1/PD‑L1: Adults with locally advanced or metastatic urothelial carcinoma previously treated with platinum chemotherapy and anti–PD‑1/PD‑L1 therapy; dosing per EV‑201 (1.25 mg/kg IV on Days 1, 8, 15 of a 28‑day cycle).

EV‑201 cohort: ORR 44%, median DoR 7.6 months.

Padcev + pembrolizumab for first‑line cisplatin‑ineligible mUC: Treatment‑naïve metastatic urothelial carcinoma patients who are ineligible for cisplatin receiving enfortumab vedotin plus pembrolizumab per EV103/Keynote‑869 dosing; evidence: ORR 68% and median DoR up to 22 months in cohorts.

Padcev neoadjuvant/adjuvant in MIBC: Previously untreated muscle‑invasive bladder cancer (predominant urothelial histology) candidates for radical cystectomy who are ineligible for or refuse cisplatin; perioperative enfortumab + pembrolizumab per EV‑303 showed improved EFS and OS versus immediate surgery.

Trial excluded primary non‑bladder urothelial cancers and patients with active autoimmune disease requiring systemic therapy within 2 years.

Datroway coverage criteria

Datroway covered when matching trial populations and biomarker/status restrictions:

Datroway for unresectable/metastatic TNBC: Adults ≥18 with unresectable or metastatic triple‑negative breast cancer without prior systemic therapy for metastatic disease; includes PD‑L1‑negative tumors and PD‑L1‑positive patients ineligible for PD‑1/PD‑L1 inhibitors; ECOG ≤1; excluded ILD/pneumonitis and clinically significant corneal disease; dosing 6 mg/kg IV every 3 weeks per TROPION‑Breast02 (ORR 64%, median PFS 10.8 vs 5.6 months).

Datroway for previously treated EGFR‑mutated NSCLC: Adults ≥18 with locally advanced or metastatic EGFR‑mutated NSCLC after prior EGFR‑directed therapy and platinum chemotherapy; evidence from TROPION‑Lung trials showed confirmed ORR ~45% and median DoR ~6.5 months; dosing per trial and prescribing information.

Mylotarg coverage criteria

Gemtuzumab ozogamicin (Mylotarg) coverage aligned to studied AML populations:

Mylotarg in newly diagnosed AML (combination): Use with standard induction chemotherapy in selected newly diagnosed de novo AML patients (per ALFA‑0701 dosing: 3 mg/m2 on Days 1, 4, 7) where EFS benefit was observed.

Mylotarg monotherapy in older/unfit AML: Monotherapy for older or unfit patients not candidates for intensive chemotherapy per AML‑19 trial showing OS benefit versus best supportive care; dosing varied by trial and selection should match trial eligibility.

Mylotarg for relapsed CD33+ AML: Use in CD33‑positive relapsed or refractory AML per MyloFrance‑1 single‑arm data documenting CRs in a subset; selection should match trial criteria and consider HSCT timing and safety risks.

Trial-aligned coverage considerations by agent

Coverage considerations informed by pivotal trials and indications

Enfortumab vedotin (Padcev) + pembrolizumab: EV103/Keynote‑869 and EV‑303 data demonstrate high ORR (68%) in cisplatin‑ineligible locally advanced/metastatic urothelial carcinoma and improved EFS/OS when used neoadjuvantly plus adjuvantly around radical cystectomy in selected MIBC patients; trial populations excluded non‑bladder primary urothelial cancers and recent systemic immunosuppression.

Polatuzumab vedotin (Polivy): Phase Ib/II and Phase II trials show improved PET‑CR and ORR when added to bendamustine/rituximab or as part of R/G‑CHP in frontline DLBCL expansion cohorts, with supportive ORR and CR rates in selected populations.

Tisotumab vedotin (Tivdak): innovaTV‑204 single‑arm trial in recurrent/metastatic cervical cancer after ≤2 prior systemic regimens showed confirmed ORR 24% and median DOR 8.3 months; trial excluded patients with active ocular surface disease and prior relevant ocular disorders.

Loncastuximab (Zynlonta): LOTIS‑2 single‑arm trial in relapsed/refractory DLBCL after ≥2 prior regimens showed ORR 48.3% and median DOR 10.3 months in a primarily ECOG 0‑1 population.

Mirvetuximab (Elahere): Study 0417 in platinum‑resistant ovarian/fallopian/peritoneal cancers required FRα positivity and prior bevacizumab; reported ORR 31.7% and median DOR 6.9 months and described ocular and other toxicities that should be monitored.

Inotuzumab (Besponsa) and Gemtuzumab (Mylotarg) safety considerations: Notable safety signals include hepatotoxicity/veno‑occlusive disease with inotuzumab (particularly around HSCT) and myelosuppression/bleeding/VOD risk with gemtuzumab in certain contexts; plan for HSCT timing and monitoring.

Drug-specific coverage updates

Policy coverage follows FDA‑approved indications and NCCN guidance; specific criteria were added or updated for individual ADCs as follows.

Padcev updates: Updated to include use in combination with pembrolizumab (and later pembrolizumab plus berahyaluronidase alfa) for locally advanced or metastatic urothelial cancer and expanded to include neoadjuvant/adjuvant MIBC when cisplatin‑ineligible.

Mylotarg pediatric expansion: Expanded pediatric indication added for newly diagnosed CD33‑positive AML in individuals 1 month and older.

Zynlonta addition: Added for relapsed or refractory large B‑cell lymphoma after two or more lines of systemic therapy.

Elahere addition: Added for adults with FRα‑positive, platinum‑resistant epithelial ovarian, fallopian tube, or primary peritoneal cancer who received 1–3 prior systemic regimens.

Datroway addition: Coverage criteria added for Datroway including unresectable/metastatic TNBC and EGFR‑mutated NSCLC indications per prescribing information and trial data.

Besponsa age update: Age requirement updated to ≥1 year for inotuzumab ozogamicin.

Prior Authorization, Documentation, and Authorization Lengths

Prior Authorization

Prior authorization and approval lengths

Prior authorization is required. Initial approvals vary by drug: Besponsa (inotuzumab ozogamicin) and Mylotarg (gemtuzumab ozogamicin) may be approved up to 3 months initially; many ADCs (including Adcetris, Datroway, Elahere, Emrelis, Padcev, Polivy, Tivdak, and Zynlonta) may be approved up to 6 months initially, with re-authorization possible up to 12 months when drug-specific criteria are met and chart notes document continued positive clinical response.

Initial approval examples: Besponsa and Mylotarg up to 3 months.
Re-authorization: many ADCs up to 6 months; may be approved up to 12 months with ongoing positive response and when criteria are met.

Prior Authorization

Document prior therapy and regimen when requesting authorization

When requesting authorization, document prior systemic therapies relevant to the indication. For PADCEV in metastatic urothelial carcinoma, prior receipt of platinum chemotherapy and a PD‑1/PD‑L1 inhibitor is required for the single-agent mUC indication; for neoadjuvant/adjuvant PADCEV regimens document cisplatin-ineligibility or refusal as per trial eligibility.

Document prior platinum chemotherapy and prior PD‑1/PD‑L1 therapy for PADCEV single‑agent mUC indication.
For PADCEV neoadjuvant/adjuvant use, document cisplatin ineligibility or refusal consistent with EV-303 trial eligibility.

Prior Authorization

Prior authorization must include indication, prior lines, ECOG, prior regimens, and tests

Include the indication, prior lines of therapy, ECOG performance status, the exact prior regimens (e.g., platinum agents, prior CAR‑T, prior bevacizumab where required), and relevant pathology/biomarker test results in the prior authorization submission to match trial-based indications.

Indication and number of prior systemic therapy lines.
ECOG status and prior specific regimens (platinum, PD‑1/PD‑L1, CAR‑T, prior bevacizumab for Elahere).
Relevant pathology/histology and biomarker assay results to match trial eligibility.

Prior Authorization

Authorization duration and adherence to FDA dosing

Non‑formulary exception review authorizations for drugs in this policy may be approved for up to 12 months; all medications are subject to the product's FDA dosing and administration prescribing information and must be administered consistent with labeling.

Non‑formulary exception approvals may be granted for up to 12 months.
Medications must be used consistent with FDA dosage and administration prescribing information.

Step Therapy

Prior therapy requirements (lines or ineligibility)

Some ADC coverage requires prior lines of therapy or documented ineligibility for alternatives. For example, PADCEV single‑agent mUC coverage requires prior platinum chemotherapy and PD‑1/PD‑L1 therapy; Elahere requires prior bevacizumab and documented FRα positivity per the specified assay.

PADCEV (mUC): prior platinum chemotherapy and prior PD‑1/PD‑L1 required for single‑agent indication.
Elahere: prior bevacizumab required and FRα positivity per VENTANA FOLR1 RxDx Assay.

Step Therapy

Sequencing considerations: follow trial-based sequencing

Sequence therapies per studied populations when applicable. PADCEV is evaluated after platinum and PD‑1/PD‑L1 therapy for the single‑agent mUC indication and is evaluated as first‑line in cisplatin‑ineligible patients only when given with pembrolizumab per EV103/Keynote-869 cohorts.

PADCEV single‑agent mUC: use after prior platinum and PD‑1/PD‑L1 agents (EV-201).
PADCEV + pembrolizumab: first‑line option for cisplatin‑ineligible metastatic urothelial carcinoma per EV103 cohorts.

Step Therapy

Step therapy considerations informed by NCCN sequences

NCCN‑referenced therapy sequences for relapsed/refractory ALL and AML are summarized in the policy and should be used to inform step therapy decisions; document prior appropriate targeted or cytotoxic regimens when applicable.

Follow NCCN therapy sequences for r/r ALL and AML when evaluating step therapy.
Document prior targeted agents or cytotoxic regimens (e.g., agents listed in NCCN tables) to support coverage decisions.

Note

Documentation Required

Required clinical documentation — general medical records

Submit complete medical records demonstrating that medical necessity criteria are met. Required documentation includes office visit notes with diagnosis, relevant history, physical exam, and medication history as part of the authorization request.

Office visit notes containing diagnosis, relevant history, physical evaluation, and medication history must be included.
Medical records should support that drug‑specific coverage criteria are met.

Documentation Required

Required documentation of tumor biomarker status and prior therapies

Provide tumor biomarker test results and prior therapy documentation as required by the indication. For Elahere, submit FRα positivity confirmed by the VENTANA FOLR1 (FOLR1‑2.1) RxDx Assay and documentation of prior bevacizumab; for Emrelis submit evidence of high c‑Met overexpression per trial definition.

Elahere: FRα positivity per VENTANA FOLR1 RxDx Assay and record of prior bevacizumab.
Emrelis: testing confirming high c‑Met overexpression (e.g., ≥50% tumor cells with strong 3+ IHC) as used in trials.

Documentation Required

Document clinical trial inclusion/exclusion characteristics

Document clinical trial inclusion/exclusion characteristics when aligning use to trial-based indications: prior lines of therapy, performance status (ECOG), histology, prior platinum exposure, and other exclusion criteria (e.g., corneal disorders, ILD) where specified.

Record prior lines of therapy, ECOG performance status, and tumor histology.
Document exclusions such as corneal disorders, Grade >1 peripheral neuropathy, or ILD/pneumonitis when applicable (e.g., Elahere trial exclusions).

Documentation Required

Follow the policy’s Documentation Requirements table

A Documentation Requirements table was added to the policy; providers must follow the policy's listed documentation requirements when requesting authorization and include the specific items noted in the policy.

Follow the Documentation Requirements table in the policy for each authorization request.
Include all items listed in the policy (office visit notes, diagnosis, history, exam, med history, biomarker results, prior regimens).

Denial Risk

Insufficient documentation may lead to denial

If submitted medical records do not show that the medical necessity criteria are met (for example, missing office visit notes with diagnosis, relevant history, physical exam, or medication history), the request may be denied for insufficient documentation.

Insufficient or missing medical records demonstrating medical necessity may trigger denial.
Ensure office visit notes and supporting documentation are included in the submission.

Denial Risk

Missing biomarker tests or excluded comorbidities may cause denial

Patients lacking required biomarker testing or with excluded comorbidities will not meet trial eligibility and may be denied coverage. Examples: absence of FRα testing per the VENTANA FOLR1 RxDx Assay for Elahere or presence of corneal disorders/other excluded conditions may trigger denial.

Absence of required FRα testing per the specified assay for Elahere risks denial.
Excluded comorbidities (e.g., corneal disorders, ocular conditions requiring ongoing treatment) listed in trial criteria may result in denial.

Denial Risk

Population eligibility risks for neoadjuvant/adjuvant use

Use in neoadjuvant/adjuvant trial populations requires meeting trial eligibility such as cisplatin ineligibility or refusal for PADCEV perioperative use; deviations from these population criteria may risk denial.

For neoadjuvant/adjuvant PADCEV + pembrolizumab use in MIBC, document cisplatin ineligibility or refusal per EV‑303 trial eligibility.
Trial exclusions (e.g., non‑bladder urothelial primaries, recent systemic immunosuppression) must be considered and documented.

Note

Benefit limitations and plan applicability — check member benefits

Coverage is subject to the limits and conditions of the member benefit plan. Providers and members should consult the member benefit booklet or customer service to determine applicability; this policy does not apply to Medicare Advantage plans.

Verify member benefit plan coverage and any plan‑specific limits or conditions before initiating therapy.
This policy explicitly does not apply to Medicare Advantage.

Approved Regimens and Dosing Schedules

Regimen	Indication / population	Dosing (as studied)	Coverage status
Adcetris (brentuximab vedotin) in combination with standard multi-agent chemotherapy regimens (including AVE-PC)	Pediatric individuals aged 2 to <22 years with previously untreated high‑risk classical Hodgkin lymphoma (Ann Arbor Stage IIB with bulk, IIIB, IVA, IVB) and adults with labeled cHL/PTCL indications	Per prescribing/trial regimens; example: AVE‑PC backbone in pediatrics with Adcetris per labeling; single‑agent/post‑HSCT dosing 1.8 mg/kg IV every 3 weeks where applicable	Covered

Regimen	Indication / population	Dosing (as studied)	Coverage status
Polivy (polatuzumab vedotin‑piiq) + rituximab + cyclophosphamide + doxorubicin + prednisone (R‑CHP)	Previously untreated diffuse large B‑cell lymphoma (DLBCL) NOS or high‑grade B‑cell lymphoma (HGBL) with International Prognostic Index (IPI) ≥ 2	Polatuzumab incorporated into R‑CHP backbone as evaluated in Phase Ib/II trials (recommended dose in expansion cohorts 1.8 mg/kg IV q21 days alongside R‑CHP)	Covered

Regimen	Indication / population	Dosing (as studied)	Coverage status
Enfortumab vedotin (Padcev) monotherapy	Adults with locally advanced or metastatic urothelial carcinoma previously treated with platinum chemotherapy and anti–PD‑1/PD‑L1 therapy	1.25 mg/kg IV on Days 1, 8, and 15 of a 28‑day cycle (per EV‑201 cohort)	Covered

Regimen	Indication / population	Dosing (as studied)	Coverage status
Enfortumab vedotin (Padcev) + pembrolizumab (with or without berahyaluronidase alfa)	Cisplatin‑ineligible individuals with previously untreated locally advanced or metastatic urothelial carcinoma; also studied as neoadjuvant then adjuvant around radical cystectomy for MIBC in cisplatin‑ineligible patients	Combination dosing per EV103/Keynote‑869 and EV‑303: enfortumab 1.25 mg/kg with pembrolizumab 200 mg IV (schedule per trial); neoadjuvant regimen described as enfortumab Days 1 and 8 plus pembrolizumab Day 1 of a 21‑day cycle in EV‑303 neoadjuvant cohort	Covered

Regimen	Indication / population	Dosing (as studied)	Coverage status
Mirvetuximab soravtansine (Elahere)	Adults with FRα‑positive, platinum‑resistant epithelial ovarian, fallopian tube, or primary peritoneal cancer who have received prior bevacizumab and 1–3 prior systemic regimens	6 mg/kg IV every 3 weeks based on adjusted ideal body weight (as used in Study 0417)	Covered

Regimen	Indication / population	Dosing (as studied)	Coverage status
Datopotamab deruxtecan (Datroway)	Unresectable or metastatic triple‑negative breast cancer (TNBC); trial enrolled individuals without prior systemic therapy for metastatic disease and excluded ECOG >1 and selected pulmonary/corneal comorbidities	6 mg/kg IV every 3 weeks (as used in TROPION‑Breast02)	Covered

Regimen	Indication / population	Dosing (as studied)	Coverage status
Enfortumab vedotin (Padcev) + pembrolizumab (± berahyaluronidase alfa)	Locally advanced or metastatic urothelial carcinoma (systemic‑therapy‑naïve cisplatin‑ineligible cohorts) and neoadjuvant/adjuvant use for muscle‑invasive bladder cancer (MIBC) in cisplatin‑ineligible patients as evaluated in EV103/Keynote‑869 and EV‑303	Per EV103/Keynote‑869 and EV‑303 trial regimens: enfortumab dosing 1.25 mg/kg with pembrolizumab 200 mg IV on trial schedules; EV‑303 neoadjuvant: enfortumab Days 1 and 8 plus pembrolizumab Day 1 of a 21‑day cycle for 3 cycles prior to surgery, then adjuvant continuation per protocol	Covered

Regimen	Indication / population	Dosing (as studied)	Coverage status
Polatuzumab vedotin (Polivy) + bendamustine + rituximab (BR) OR Polivy incorporated into R/G‑CHP backbone	Relapsed or refractory DLBCL for Polivy+BR; previously untreated DLBCL with IPI 2–5 in expansion cohorts for Polivy+R/G‑CHP	Polivy + BR dosing per ongoing trials (polatuzumab dose example in BR studies 2.4 mg/kg IV q21 days in earlier trials); Polivy in R/G‑CHP evaluated at 1.8 mg/kg IV q21 days in dose‑expansion cohorts	Covered

Regimen	Indication / population	Dosing (as studied)	Coverage status
Tisotumab vedotin (Tivdak)	Adults with recurrent or metastatic cervical cancer with disease progression on or after chemotherapy (≤2 prior systemic regimens in the recurrent/metastatic setting)	2 mg/kg IV every 3 weeks (as used in innovaTV 204)	Covered

Regimen	Indication / population	Dosing (as studied)	Coverage status
Loncastuximab tesirine (Zynlonta) dosing schedule from LOTIS‑2	Adults with relapsed or refractory diffuse large B‑cell lymphoma (DLBCL) after ≥2 prior systemic regimens	0.15 mg/kg IV every 3 weeks for 2 cycles, then 0.075 mg/kg IV every 3 weeks for subsequent cycles (per LOTIS‑2)	Covered

Regimen	Indication / population	Dosing (as studied)	Coverage status
Enfortumab vedotin‑ejfv + pembrolizumab (with or without berahyaluronidase alfa) combination regimens	Adults with locally advanced or metastatic urothelial cancer who are cisplatin‑ineligible; also evaluated in neoadjuvant/adjuvant MIBC when cisplatin‑ineligible per EV‑303	Combination regimens per clinical trials (EV103/Keynote‑869 and EV‑303) with enfortumab 1.25 mg/kg and pembrolizumab 200 mg IV on trial schedules; berahyaluronidase alfa included in amended indications per updated approvals	Covered

Regimen	Indication / population	Dosing (as studied)	Coverage status
Loncastuximab tesirine (Zynlonta) per prescribing information for relapsed/refractory large B‑cell lymphoma	Adults with relapsed or refractory large B‑cell lymphoma (including DLBCL NOS, DLBCL arising from low‑grade lymphoma, HGBL) after ≥2 prior systemic therapies	LOTIS‑2 schedule: 0.15 mg/kg IV q3w for 2 cycles then 0.075 mg/kg IV q3w thereafter; use per prescribing information	Covered

Required Biomarker Testing and Definitions

Folate receptor alpha (FRα) — FRα-positive per labeling

BiomarkerFolate receptor alpha (FRα)

Required forElahere (mirvetuximab soravtansine-gynx)

Threshold/DefinitionFRα-positive (as per labeling)

Age requirement (agent-specific)Adults aged ≥18 years for Elahere

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

Biomarkerc-Met protein overexpression

Required forEmrelis (telisotuzumab vedotin-tllv)

Threshold/Definition>=50% of tumor cells with strong (3+) staining by immunohistochemistry (IHC)

TestingHigh c‑Met overexpression identified by central or validated assays per trial

FRα (FOLR1) positive per VENTANA FOLR1 (FOLR1-2.1) RxDx Assay as used in Study 0417

AssayVENTANA FOLR1 (FOLR1-2.1) RxDx Assay

ContextUsed to determine FRα positivity for Study 0417 (Elahere) enrollment

Population requirementIndividuals enrolled had FRα-positive tumors per this assay

c-Met protein overexpression — high OE defined in trial (e.g., ≥50% tumor cells with strong 3+ staining)

Biomarkerc-Met protein overexpression (trial definition)

Threshold/DefinitionHigh overexpression defined as ≥50% of tumor cells with strong (3+) membrane and/or cytoplasmic staining

ConfirmationRetesting with VENTANA MET (SP44) RxDx assay showed concordance in trial samples

CD22 — ≥70% leukemic blasts expressing CD22 by flow cytometry

BiomarkerCD22 expression on leukemic blasts

Required forBesponsa (inotuzumab ozogamicin) per INO-VATE ALL trial

Threshold/Definition>=70% leukemic blasts expressing CD22 by flow cytometry

PopulationAdults with relapsed/refractory B‑cell precursor ALL in trial enrollment

Nectin-4 — biomarker for enfortumab vedotin

BiomarkerNectin-4 expression

Required forEnfortumab vedotin (Padcev) mechanism/target

NotesADC binds Nectin-4–expressing cells leading to internalization and release of MMAE payload

CD19; CD30 — example ADC targets referenced in definitions/trials

Examples of ADC targetsCD19 (e.g., loncastuximab tesirine / Zynlonta)

Examples of ADC targetsCD30 (e.g., brentuximab vedotin / Adcetris)

NoteThese antigens are referenced in agent mechanisms and trial contexts

CD33 — biomarker for CD33-directed ADCs (e.g., gemtuzumab)

BiomarkerCD33 expression

Required forGemtuzumab ozogamicin (Mylotarg) in AML

ContextReferenced in NCCN guidance and trial enrollment for CD33‑positive AML

FRα (folate receptor alpha) — positive (short note)

BiomarkerFolate receptor alpha (FRα)

MeaningPositive (indicates eligibility for FRα‑directed therapy such as Elahere)

Clinical useFRα positivity required per labeling and Study 0417 assay specification

c-Met protein overexpression — high overexpression (short note)

Biomarkerc-Met protein overexpression

MeaningHigh overexpression (trial-defined threshold informs Emrelis eligibility)

Clinical useUsed to select non-squamous NSCLC patients for telisotuzumab vedotin therapy

EGFR mutation — EGFR-mutated NSCLC indication (biomarker-linked)

Biomarker-linked indicationEGFR mutation used to select patients for certain ADC indications (Datroway in EGFR‑mutated NSCLC)

ContextDatroway indication expanded to include locally advanced/metastatic EGFR‑mutated NSCLC after prior EGFR‑directed therapy and platinum chemotherapy

DocumentationPrescribed by or in consultation with an oncologist per policy criteria

HCPCS and J-Code Assignments

HCPCS codes (new)HCPCS

C9174	Injection, datopotamab deruxtecan-dlnk (Datroway), 1 mg (code termed 10/01/25)
C9306	Injection, telisotuzumab vedotin-tllv (Emrelis), 1 mg (code termed 01/01/26)

Covered J-codesHCPCSCovered

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
J9326	Injection, telisotuzumab vedotin-tllv, 1 mg (new code effective 01/01/26)
J9359	Injection, loncastuximab tesirine-lpyl (Zynlonta), 0.075 mg

HCPCS and historical coding changesHCPCS

J9229	HCPCS code added effective 1/1/19 (referenced in historical changes)
J3590	HCPCS — added/removed at different times; referenced for certain ADCs historically
C9084	HCPCS code (deleted/termed as noted in history)
J9177	HCPCS code added (Adcetris)
J9273	HCPCS code added
J9359	HCPCS code added
C9146	HCPCS code added then later removed
J9063	HCPCS code added
J9042	HCPCS code added for Adcetris
J9309	HCPCS code added for Polivy

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Approved Lines of Therapy

Varies — 1 top-level node indicating variability by agent/indication

Coverage and line‑of‑therapy considerations vary by agent and indication.

Varies by agent/indication: Line of therapy is agent‑specific: examples include Padcev used as neoadjuvant/adjuvant for MIBC in cisplatin‑ineligible patients and for mUC as single agent after prior therapies or in combination as first‑line for cisplatin‑ineligible patients; Zynlonta and Polivy have distinct line‑of‑therapy placements per their labeled indications and trial cohorts.

first-line | second-line | salvage

Line‑of‑therapy categories used in trial‑aligned criteria:

First‑line: Used for selected indications/trials (e.g., Polivy + R‑CHP for previously untreated DLBCL with IPI ≥2; Padcev + pembrolizumab in cisplatin‑ineligible first‑line mUC cohorts).

Second‑line: Used for agents studied after prior systemic therapy (e.g., Padcev single‑agent for mUC after prior platinum and PD‑1/PD‑L1 therapy; many agents are indicated after specified prior lines).

Salvage: Used for relapsed/refractory settings (e.g., Besponsa in r/r ALL; Zynlonta and many lymphoma ADCs in relapsed/refractory disease after multiple prior regimens).

second-line — agent-specific second-line notes

Second‑line examples (agent‑specific):

Padcev second‑line mUC: Adults with locally advanced or metastatic urothelial carcinoma previously treated with platinum chemotherapy and anti‑PD‑1/PD‑L1 therapy (EV‑201 cohort).

first-line — agent-specific first-line notes

First‑line examples (agent‑specific):

Padcev + pembrolizumab first‑line cisplatin‑ineligible: No prior systemic therapy for metastatic disease and ineligible for cisplatin‑containing chemotherapy (EV103/Keynote‑869 cohorts).

salvage — salvage therapy node

Salvage therapy node (examples):

Besponsa salvage use in r/r ALL: Relapsed/refractory adult ALL per INO‑VATE ALL eligibility (fractionated inotuzumab dosing, CD22 expression requirement).

mixed — agents with mixed line indications (3 top-level nodes)

Mixed line indications — examples by agent:

Enfortumab vedotin combinations: Evaluated as first‑line in cisplatin‑ineligible metastatic urothelial carcinoma in combination with pembrolizumab, and as neoadjuvant/adjuvant in MIBC; also studied in previously treated mUC cohorts.

Tisotumab vedotin: Used in recurrent/metastatic cervical cancer after ≤2 prior systemic regimens (trial population).

Loncastuximab (Zynlonta): Used in relapsed/refractory DLBCL after ≥2 prior systemic regimens (LOTIS‑2 trial).

second-line_or_later — agent-specific

Second‑line or later examples (agent‑specific):

Zynlonta second‑line_or_later: Relapsed or refractory large B‑cell lymphoma after ≥2 lines of systemic therapy (per LOTIS‑2 and labeling).

second-line_or_later — agent-specific (additional reference)

Second‑line or later examples (additional):

Elahere second‑line_or_later: Adults with FRα‑positive, platinum‑resistant epithelial ovarian/fallopian tube/primary peritoneal cancer who have received 1–3 prior systemic regimens (Study 0417 population).

Key Definitions and Terms

Antibody-drug conjugate (ADC) — definition

DefinitionAntibody‑drug conjugate (ADC): a monoclonal antibody linked to a chemotherapy drug designed to target antigens on cancer cells and release cytotoxic drug intracellularly.

PurposeTarget cancer cells and limit toxicity to healthy tissue

Policy useThis policy lists ADCs and their labeled, medically necessary indications

ADC mechanism — monoclonal antibody linked to cytotoxic agent (examples MMAE, SG3199)

Mechanism summaryMonoclonal antibody linked to a cytotoxic payload that binds a tumor antigen, is internalized, and releases payload via proteolytic cleavage

Payload examplesMMAE (microtubule inhibitor), SG3199 (PBD dimer)

ResultPayload disrupts target cell processes (e.g., microtubules or DNA) leading to apoptosis

Loncastuximab tesirine (Zynlonta) mechanism — CD19-directed ADC with PBD dimer payload

AgentLoncastuximab tesirine (Zynlonta)

MechanismCD19‑directed ADC composed of a humanized IgG1 kappa antibody linked to a PBD dimer (SG3199) via a valine‑alanine cleavable linker

ActionInternalization followed by release of SG3199 which forms DNA interstrand crosslinks causing cell death

ORR — objective response rate definition

TermObjective response rate (ORR)

DefinitionMeasure of the proportion of patients with tumor size reduction of a predefined amount (e.g., partial or complete responses) in trials

UseReported as primary or key secondary efficacy endpoints across ADC trials

DOR — duration of response definition

TermDuration of response (DOR)

DefinitionTime from initial documented response (CR or PR) until disease progression or death

UseReported in ADC trials (examples: Elahere median DOR 6.9 months; Emrelis median DOR 7.2 months)

Antibody-Drug Conjugate (ADC) — brief definition and examples

Definition (brief)Antibody‑Drug Conjugate (ADC): targeted therapy combining a monoclonal antibody directed at a tumor‑associated antigen with a cytotoxic payload

ExamplesBrentuximab vedotin (CD30‑MMAE), Loncastuximab tesirine (CD19‑PBD), Enfortumab vedotin (Nectin‑4‑MMAE)

Mechanism noteBinding, internalization, proteolytic release of payload to kill tumor cells

Policy Revision Timeline

2019annual_review

Literature search (1/1/18–2/28/19) found no new evidence requiring policy change; 2019 update documented in policy history.

2020policy_update

Reviewed prescribing information and added expanded pediatric indication for Mylotarg (gemtuzumab ozogamicin) for newly diagnosed CD33+ AML in individuals 1 month and older; added Investigational and Documentation Requirements tables.

2021policy_update

Added Zynlonta (loncastuximab tesirine-lpyl) for relapsed or refractory large B‑cell lymphoma after ≥2 lines of systemic therapy.

2022policy_update

Added Elahere (mirvetuximab soravtansine-gynx) for FRα‑positive, platinum‑resistant ovarian/fallopian/primary peritoneal cancer (1–3 prior regimens).

2023policy_update

Updated Padcev (enfortumab vedotin) coverage to include use in combination with pembrolizumab for locally advanced or metastatic urothelial cancer in the indicated population.

2024policy_update

Expanded Padcev criteria to include combination with pembrolizumab regardless of cisplatin eligibility and lowered Besponsa (inotuzumab) age requirement to ≥1 year.

2025policy_update

Clarified non‑formulary exception authorizations may be approved up to 12 months; added coverage criteria for Datroway (datopotamab deruxtecan) and moved Adcetris and Polivy from policy 2.03.502 into this ADC policy; documented coding/HCPCS updates effective Oct 1, 2025 and historical coding changes.

2026policy_updateLatest

Reviewed prescribing information and updated Padcev coverage to include combination with pembrolizumab plus berahyaluronidase alfa; policy effective 2026‑08‑01 with last review 2026‑07‑14.

Antibody-Drug Conjugates

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Coverage Criteria for ADCs

Prior Authorization, Documentation, and Authorization Lengths

Approved Regimens and Dosing Schedules

Required Biomarker Testing and Definitions

HCPCS and J-Code Assignments

Approved Lines of Therapy

Background on Antibody-Drug Conjugates

Key Definitions and Terms

Policy Revision Timeline