ModifiedPremera BluecrossPolicy N/A

Antibody-Drug Conjugates (ADCs) medical necessity and coverage

Defines medical necessity criteria, coding, documentation, and approval durations for specific FDA-labeled antibody-drug conjugates managed under the medical benefit; intended for providers and payers.

Policy Summary

PayerPremera Bluecross

PolicyAntibody-Drug Conjugates (ADCs) medical necessity and coverage

Policy CodePolicy N/A

Change TypeModified — includes additions and revisions (Datroway addedPadcev combinations expandedage criteria for Besponsa revised)

Effective DateFeb 1, 2026

Next Review DateN/A

Key ActionObtain prior authorization and document indication, prior lines of therapy, and required biomarker test results per product label.

SourceLink

POLICY UPDATE CHANGES

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

Updated Padcev coverage to include combination with pembrolizumab and berahyaluronidase alfa-pmph for locally advanced or metastatic urothelial cancer.

Updated Besponsa age requirement to include individuals 1 year of age and older.

Non-formulary exception review authorizations for all drugs listed may be approved up to 12 months.

Moved Adcetris and Polivy into this ADC policy from the Monoclonal Antibodies for the Treatment of Lymphoma policy.

Updated coverage criteria for Padcev (enfortumab vedotin-ejfv) to include combination with pembrolizumab and berahyaluronidase alfa-pmph for locally advanced or metastatic urothelial cancer.

Reviewed and updated prescribing information for all drugs listed in this policy.

12+ADC products listed with coverage criteria

Up to 12 monthsTypical initial approval duration

Trek Health ingests and normalizes Transparency in Coverage data and payer policy updates to give provider organizations a clear view of how commercial reimbursement behaves across markets, payers, and services. Our platform transforms raw payer disclosures into structured intelligence that supports contract evaluation, payer negotiations, and service line strategy. By combining market benchmarks with ongoing policy visibility, Trek helps teams identify variability, risk, and opportunity in commercial reimbursement. The result is faster insight, stronger negotiating positions, and more informed financial decisions.

Multiple HCPCS/J-codesSpecific billing codes listed

80.7%CR/CRi rate with inotuzumab (INO-VATE)

14%Besponsa hepatotoxicity/VOD incidence

Padcev expandedPadcev expanded

Coverage Criteria for Antibody-Drug Conjugates (ADCs)

Adcetris (brentuximab vedotin) — covered indications

Covered when agent-specific labeled indications or specified criteria are met

Adcetris labeled indications: Adcetris (brentuximab vedotin) may be considered medically necessary for the following labeled indications: 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 classical Hodgkin lymphoma at high risk of relapse/progression; classical Hodgkin lymphoma after failure of auto-HSCT or after failure of ≥2 prior multi-agent chemotherapy regimens in individuals not eligible for auto-HSCT; 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 chemotherapy regimen; primary cutaneous ALCL or CD30-expressing mycosis fungoides after prior systemic therapy; relapsed/refractory large B-cell lymphoma (including DLBCL and HGBL) after ≥2 lines of systemic therapy in individuals not eligible for auto-HSCT or CAR T-cell therapyagent- and indication-specific

Follow FDA prescribing information for dosing and monitoring.

Other ADCs — illustrative agent-specific criteria

Covered when ALL agent-specific listed criteria are met (examples shown below; full policy contains complete per-agent criteria)

Datroway (breast cancer): Individual aged ≥18 AND unresectable or metastatic HR-positive, HER2-negative breast cancer AND has received prior endocrine-based therapy and chemotherapy for unresectable/metastatic disease AND prescribed by or in consultation with an oncologistage >=18

See Datroway criteria and TROPION-Breast01 evidence.

Datroway (NSCLC): Individual aged ≥18 AND locally advanced or metastatic EGFR-mutated NSCLC AND has received prior EGFR-directed therapy and platinum-based chemotherapyage >=18; EGFR-mutated

See Datroway NSCLC subgroup evidence.

Elahere (mirvetuximab) epithelial ovarian cancer: Individual aged ≥18 AND folate receptor alpha (FRα) positive platinum-resistant epithelial ovarian, fallopian tube, or primary peritoneal cancer AND prior bevacizumab and up to 3 prior systemic therapies as applicableFRα positive by specified assay; age >=18

FRα positivity determined by VENTANA FOLR1 RxDx Assay per trial eligibility.

Adcetris (brentuximab vedotin) — Study 3

Classical Hodgkin lymphoma — post-autologous HSCT consolidation (Adcetris)

Adcetris post-auto-HSCT consolidation trial eligibility: Adults with classical Hodgkin lymphoma at high risk of relapse or progression after autologous HSCT (high risk defined as refractory to frontline therapy; relapse within 12 months; or relapse ≥12 months with extranodal disease) AND achieved CR, PR, or SD to most recent salvage therapy AND treatment initiated 30–45 days post-auto-HSCT; dosing 1.8 mg/kg IV every 3 weeks up to 16 cycles

Primary endpoint PFS improved vs placebo per independent review.

Adcetris (brentuximab vedotin) — Study 2

Relapsed systemic anaplastic large cell lymphoma (sALCL) — single-arm evidence

Adcetris in relapsed sALCL eligibility: Patients with relapsed systemic ALCL after prior therapy AND treated with Adcetris 1.8 mg/kg IV every 3 weeks; efficacy assessed by ORR and duration of response using CT and PET per lymphoma response criteria

Study population median age 52; 72% ALK-negative.

Inotuzumab ozogamicin — INO-VATE ALL

Relapsed/refractory acute lymphoblastic leukemia (inotuzumab ozogamicin)

INO-VATE ALL eligibility: Adults ≥18 with relapsed or refractory ALL AND ≥70% leukemic blasts expressing CD22 by flow cytometry AND randomized to inotuzumab 1.8 mg/m2 per cycle (fractionated schedule: 0.8 mg/m2 Day 1; 0.5 mg/m2 Days 8 and 15) versus investigator-choice chemotherapyCD22 >=70%

Primary endpoints CR/CRi and OS; higher CR/CRi and MRD-negativity observed with inotuzumab.

Datroway (datopotamab deruxtecan)

Datopotamab deruxtecan (Datroway) trial evidence

Datroway efficacy summaries: Breast cancer: Phase 3 TROPION-Breast01 showed median PFS 6.9 vs 4.9 months and ORR 36% vs 23% versus chemotherapy; recommended dose 6 mg/kg (max 540 mg) IV q3 weeks. NSCLC: pooled and Phase II/III data showed confirmed ORR ~45% in previously treated locally advanced/metastatic EGFR‑mutated NSCLC with median DOR ~6.5 months

See prescribing information for dosing limits and trial details.

Elahere (mirvetuximab soravtansine)

FRα-positive, platinum-resistant epithelial ovarian, fallopian tube, or primary peritoneal cancer — Elahere

Elahere eligibility: Adults aged ≥18 with FRα-positive, platinum-resistant epithelial ovarian, fallopian tube, or primary peritoneal cancer as determined by the VENTANA FOLR1 (FOLR1-2.1) RxDx Assay AND permitted up to 3 prior systemic therapies AND prior bevacizumab required AND excluded if corneal disorders, ocular conditions requiring ongoing treatment, Grade >1 peripheral neuropathy, or noninfectious interstitial lung disease; dosing 6 mg/kg IV q3 weeksFRα positive by VENTANA assay; age >=18

Confirmed ORR 31.7% and median DOR 6.9 months in Study 0417.

Emrelis (telisotuzumab vedotin)

c-Met overexpressing non-small cell lung cancer — Emrelis

Emrelis eligibility: Adults aged ≥18 with locally advanced or metastatic non-squamous, EGFR-wildtype NSCLC AND tumor demonstrates high c-Met protein overexpression (defined as ≥50% of tumor cells with strong 3+ membrane and/or cytoplasmic staining by validated assay) AND has received prior systemic therapy (no more than one prior chemotherapy line in advanced setting)c-Met >=50% 3+

LUMINOSITY showed ORR ~35% and median DOR 7.2 months; confirmatory testing by VENTANA MET (SP44) RxDx assay where indicated.

Gemtuzumab ozogamicin (historical and later trials)

Gemtuzumab ozogamicin evidence in AML

Gemtuzumab ozogamicin studies: Historical and later trials support use in CD33-positive AML including early phase II studies leading to accelerated approval, randomized trials (ALFA-0701, AML-19) showing EFS or OS benefit in select populations, and MyloFrance-1 single-arm data in relapsed/refractory CD33-positive AML; dosing and populations varied across studiesCD33-positive AML per label

Safety concerns previously led to withdrawal; subsequent data supported reintroduction.

Padcev (enfortumab vedotin)

Enfortumab vedotin evidence in urothelial carcinoma

Padcev advanced/metastatic eligibility: Adults with locally advanced or metastatic urothelial carcinoma previously treated with platinum chemotherapy and anti–PD-1/PD-L1 therapy AND dosing per label (e.g., 1.25 mg/kg Days 1, 8, 15 of 28-day cycle)Prior platinum and PD-1/PD-L1 exposure

EV-201 cohort 1 ORR 44% with median DOR 7.6 months.

Padcev combination (neoadjuvant/adjuvant) for MIBC: Adults aged ≥18 with muscle-invasive bladder cancer who are ineligible for cisplatin-containing chemotherapy AND receive neoadjuvant Padcev 1.25 mg/kg IV Days 1 and 8 plus pembrolizumab 200 mg IV q21 days for 3 cycles followed by radical cystectomy and adjuvant Padcev and pembrolizumab per trial schema; trial showed improved EFS and OS vs immediate surgeryAdult, cisplatin-ineligible

See EV-303 trial design and outcomes.

Polivy (polatuzumab vedotin)

Polatuzumab vedotin in diffuse large B-cell lymphoma

Polivy trial summaries: Polatuzumab vedotin demonstrated antitumor activity in R/R DLBCL when combined with bendamustine + rituximab (higher PET-CR and ORR vs BR) and promising activity in combination with R-CHP in treatment‑naïve DLBCL (dose-expansion at 1.8 mg/kg q21 days with high ORR/CR and favorable 12- and 24-month PFS estimates)

Use per labeled combinations and trial-derived dosing.

Tivdak (tisotumab vedotin)

Tisotumab vedotin (Tivdak) for recurrent/metastatic cervical cancer

Tivdak eligibility: Adults aged ≥18 with recurrent or metastatic cervical cancer AND disease progression on or after prior systemic therapy AND no more than 2 prior systemic regimens in the recurrent/metastatic setting (including a prior platinum) AND excluded for active ocular surface disease, prior cicatricial conjunctivitis, Grade ≥2 peripheral neuropathy, or bleeding risk<=2 prior systemic regimens; age >=18

Dosing 2 mg/kg IV q3 weeks; confirmed ORR 24% in innovaTV 204.

Zynlonta (loncastuximab tesirine)

Relapsed/refractory DLBCL — Zynlonta (LOTIS-2)

Zynlonta eligibility: Adults with relapsed or refractory large B-cell lymphoma after at least 2 prior systemic regimens AND without bulky disease or active CNS lymphoma; dosing initiation 0.15 mg/kg for 2 cycles then 0.075 mg/kg q3 weeks thereafter>=2 prior systemic regimens

LOTIS-2 confirmed ORR 48.3% and median DOR 10.3 months.

Covered ADCs per FDA-approved indications

Covered when using FDA-approved indications and meeting referenced criteria in the policy documents and prescribing information.

Padcev (enfortumab vedotin-ejfv) for mUC: Covered when used for locally advanced or metastatic urothelial cancer in accordance with updated indications including use in combination with pembrolizumab and berahyaluronidase alfa-pmph as specified in prescribing informationper FDA labeling

Coverage updated 2023–2026 to expand combinations and neoadjuvant/adjuvant use.

Besponsa (inotuzumab ozogamicin): Covered for indicated B‑cell ALL populations with age requirement revised to 1 year of age and older; follow FDA prescribing information for dosing and monitoring due to veno‑occlusive disease riskage >=1 year

Monitor for hepatotoxicity/VOD per label and trial findings.

Datroway (datopotamab deruxtecan-dlnk):

Padcev (enfortumab vedotin-ejfv) updated coverage groups

Covered when consistent with updated FDA prescribing information and specific policy criteria (examples shown in history and updates):

Padcev combinations for mUC: Use of Padcev (enfortumab vedotin-ejfv) in combination with pembrolizumab, with or without berahyaluronidase alfa-pmph, for locally advanced or metastatic urothelial cancer is included in coverage criteria per 2026 updateFDA prescribing information consistent

See policy history for updates through 2026.

Padcev neoadjuvant/adjuvant for MIBC: Coverage includes Padcev in combination with pembrolizumab (± berahyaluronidase alfa‑pmph) as neoadjuvant therapy and continued after cystectomy as adjuvant therapy for adult patients with muscle-invasive bladder cancer who are ineligible for cisplatin-containing chemotherapyAdult, cisplatin-ineligible

Based on EV-303 neoadjuvant/adjuvant trial demonstrating improved EFS and OS.

All uses of the medications listed in this policy other than the specified FDA-labeled indications are considered investigational. Coverage and authorization decisions will follow the product's FDA dosing and administration prescribing information; uses outside those labeled indications are not supported by this policy and should be considered investigational unless an exception is documented and approved.

Trial eligibility criteria and trial-specific exclusions described in pivotal studies inform coverage denials when similar exclusions are present in an individual’s clinical record. Examples include exclusion for active corneal disorders or ocular conditions requiring ongoing treatment in the Elahere trial and exclusion for active ocular surface disease or prior cicatricial conjunctivitis in the Tivdak trial. If an individual meets trial exclusion criteria that the policy uses to define eligible populations, coverage may be denied unless documentation justifies an exception.

Use of ADCs in contexts not supported by FDA labeling or outside the policy-specified indications (for example, off-label uses that are not documented in this policy) is not covered. Clinical situations associated with known, drug-specific safety risks (e.g., hepatotoxicity/VOD with inotuzumab ozogamicin) that differ from trial-supported populations also may lead to non-coverage when the record does not meet the policy’s agent-specific criteria.

This medical policy does not apply to Medicare Advantage. Coverage determinations remain subject to the member’s contract benefit limits; providers and members should consult the member benefit booklet or contact member services to confirm benefit applicability and any plan-specific limitations.

A literature search conducted from 1/1/18 to 2/28/19 found no new evidence requiring changes to the policy at that time. Absence of new or corroborating evidence for unproven indications may support non-coverage decisions for investigational or off-label uses unless later prescribing information or high-quality evidence is provided.

Billing and Coding

HCPCS / J-codes listedHCPCS

C9174	Injection, datopotamab deruxtecan-dlnk (Datroway), 1 mg (new code effective 07/01/25)
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

No explicit CPT/HCPCS/ICD-10 codes in this sectionmixed

No codes listed

ADC HCPCS/J codes mentioned in history and updatesHCPCS

J9042	Adcetris (brentuximab vedotin) HCPCS code added
J9309	Polivy (polatuzumab vedotin) HCPCS code added
C9174	Datroway HCPCS code previously added then removed
J9326	HCPCS code added effective Jan 1, 2026
J9011	HCPCS code added effective Oct 1, 2025
C9306	HCPCS code termed Oct 1, 2025
J9063	HCPCS code added Jul 2023
C9146	HCPCS code added Apr 2023 then removed Jul 2023
C9084	HCPCS code added Apr 2022
J9229	HCPCS code added Jan 1, 2019

1–10 of 12

1/2

Lines of prior therapy — Tivdak, Zynlonta

Tivdak prior therapyTypically received 1-2 prior systemic regimens (TV-204: 70% had 1 prior line; 30% had 2 prior lines)

Zynlonta prior therapyIndicated for relapsed/refractory large B-cell lymphoma after at least 2 prior systemic regimens (LOTIS-2 enrolled patients with median 3 prior therapies)

Policy summaryLine-of-therapy requirements are agent-specific and referenced in individual drug criteria; use must align with labeled indications

Prior Authorization, Documentation, and Operational Guidance

Prior Authorization

Prior Authorization Required and Approval Duration

Prior authorization is required for all drugs listed in this policy. Initial authorizations for Adcetris, Besponsa, Datroway, Elahere, Emrelis, Mylotarg, Padcev, Tivdak, and Zynlonta may be approved up to 12 months for non‑formulary exception reviews; other initial approvals vary by drug as specified in the policy. Re‑authorization may be approved only when drug‑specific coverage criteria are met and chart notes document continued clinical benefit.

Initial non‑formulary exception approvals for Adcetris, Besponsa, Datroway, Elahere, Emrelis, Mylotarg, Padcev, Tivdak, and Zynlonta: up to 12 months
Other initial approvals: Besponsa and Mylotarg other reviews up to 3 months; many other drugs up to 6 months or 12 months per drug‑specific statements

Documentation Required

Indication, Prior Therapy, and Biomarker Verification

Providers must document the indication, prior systemic therapies, and biomarker status requested for the covered indication at time of PA submission. Approvals are contingent on meeting the specific indication and prior‑therapy requirements listed for each drug (for example number of prior lines of therapy or prior bevacizumab/PARP inhibitor exposure for Elahere).

Key Definitions and Biomarker Requirements

Antibody-drug conjugate (ADC) definition

DefinitionA monoclonal antibody linked to a chemotherapy drug designed to target antigens on cancer cells and release cytotoxic agents intracellularly to spare healthy tissue.

MechanismMonoclonal antibody targets tumor-associated antigen, is internalized, and releases cytotoxic payload into cancer cells

Policy contextThis policy lists ADCs with FDA-labeled indications and the clinical contexts in which they may be medically necessary

PFS definition

PFS definitionProgression-free survival (PFS) is calculated from randomization to date of disease progression or death (due to any cause).

Context of usePrimary endpoint in randomized Adcetris post-auto-HSCT trial as assessed by independent review committee (IRF)

Agent Dosing and Regimen Tables

Regimen	Indication / Key eligibility	Coverage status
Polivy (polatuzumab vedotin-piiq) + rituximab product + cyclophosphamide, doxorubicin, prednisone (R-CHP)
Previously untreated diffuse large B-cell lymphoma (DLBCL) or high‑grade B‑cell lymphoma (HGBL) with International Prognostic Index (IPI) ≥2
Covered

Regimen	Indication / Key eligibility	Coverage status
Padcev (enfortumab vedotin-ejfv) in combination with pembrolizumab — with or without berahyaluronidase alfa-pmph — neoadjuvant then continued as adjuvant after cystectomy
Adult patients (≥18 years) with muscle‑invasive bladder cancer (MIBC) who are ineligible for cisplatin‑containing chemotherapy; used as neoadjuvant therapy then continued after cystectomy as adjuvant treatment
Covered

Regimen	Dose / schedule	Coverage status
Polatuzumab vedotin (dose‑expansion cohort) in combination with R‑CHP
1.8 mg/kg IV every 21 days (dose used in expansion cohort) per Phase Ib/II trial; administered with rituximab product + cyclophosphamide, doxorubicin, prednisone for 6–8 cycles
Informational

Regimen	Dose / schedule	Coverage status
Inotuzumab ozogamicin (fractionated schedule)
Total 1.8 mg/m2 per cycle given as 0.8 mg/m2 IV on Day 1 and 0.5 mg/m2 IV on Days 8 and 15 (fractionated schedule)
Informational

Regimen	Dose / schedule	Coverage status
Datroway (datopotamab deruxtecan-dlnk)
6 mg/kg IV every 3 weeks, maximum 540 mg per dose; continue until disease progression or unacceptable toxicity
Informational

Regimen / therapies listed	Context / indication	Coverage status
Tyrosine kinase inhibitors (FLT3, IDH, FLT3‑TKD agents per NCCN), blinatumomab, inotuzumab ozogamicin, CAR T‑cell therapies, CD33‑targeted regimens (e.g., gemtuzumab ozogamicin)
Recommended regimens for relapsed/refractory B‑ALL and AML per NCCN guidance and policy references; used in appropriate biomarker‑selected or line‑of‑therapy contexts
Informational

Agent / example	Trial dosing / label regimen	Coverage status
Zynlonta (loncastuximab tesirine-lpyl)
Initial dosing 0.15 mg/kg every 3 weeks for 2 cycles then 0.075 mg/kg every 3 weeks thereafter (LOTIS‑2 schedule)
Covered with criteria

Regimen	Indication / Key eligibility	Coverage status
Padcev (enfortumab vedotin-ejfv) + pembrolizumab, with or without berahyaluronidase alfa-pmph
Locally advanced or metastatic urothelial cancer (mUC) in adults; covered both as single agent in later‑line settings and in combination per updated labeling
Covered

Regimen	Indication / Key eligibility	Coverage status
Elahere (mirvetuximab soravtansine-gynx)
FRα‑positive, platinum‑resistant epithelial ovarian, fallopian tube, or primary peritoneal cancer after one or more prior systemic regimens; FRα positivity by VENTANA FOLR1 RxDx assay; dosing per label (6 mg/kg IV q3 weeks)
Covered with criteria

Regimen / agent	Indication / biomarker requirement	Coverage status
Emrelis (telisotuzumab vedotin-tllv)
Locally advanced or metastatic non‑squamous NSCLC with high c‑Met protein overexpression (≥50% tumor cells with strong 3+ IHC staining); adults who have received ≥1 line of systemic therapy
Covered with criteria

Regimen / agent	Indication / key eligibility	Coverage status
Datroway (datopotamab deruxtecan-dlnk)
Locally advanced or metastatic EGFR‑mutated NSCLC (new indication added per 2025 history); dosing 6 mg/kg IV q3 weeks (max 540 mg)
Covered with criteria

Background on Antibody-Drug Conjugates

Antibody-drug conjugates (ADCs) are monoclonal antibodies linked to cytotoxic payloads that target tumor-associated antigens, are internalized by tumor cells, and release their cytotoxic agents intracellularly to effect tumor cell death while limiting systemic exposure. This policy lists ADCs with FDA-labeled indications and specifies agent-, indication-, biomarker-, and line-of-therapy–specific criteria that must be met for coverage under the medical benefit.

Policy Revision History and Material Changes

2026-02-01policy_updateLatest

Reviewed prescribing information for all drugs and updated coverage criteria for Padcev (enfortumab vedotin-ejfv) to include combination with pembrolizumab and berahyaluronidase alfa-pmph for locally advanced or metastatic urothelial cancer.

2025policy_update

Reviewed prescribing information; added coverage criteria for Datroway (datopotamab deruxtecan-dlnk); clarified non-formulary exception review authorizations may be approved up to 12 months; moved Adcetris and Polivy into this ADC policy from Monoclonal Antibodies for the Treatment of Lymphoma.

Policy Summary

PayerPremera Bluecross

PolicyAntibody-Drug Conjugates (ADCs) medical necessity and coverage

Policy CodePolicy N/A

Change TypeModified — includes additions and revisions (Datroway addedPadcev combinations expandedage criteria for Besponsa revised)

Effective DateFeb 1, 2026

Next Review DateN/A

Key ActionObtain prior authorization and document indication, prior lines of therapy, and required biomarker test results per product label.

SourceLink

On This Page

Emrelis (telisotuzumab) NSCLC: Individual aged ≥18 AND locally advanced or metastatic non-squamous NSCLC AND tumor demonstrates high c-Met protein overexpression (≥50% tumor cells with strong 3+ IHC) AND has received ≥1 line of systemic therapyc-Met >=50% 3+; age >=18

High c-Met defined per VENTANA MET (SP44) RxDx Assay and trial inclusion.

Mylotarg (gemtuzumab ozogamicin) AML: Newly diagnosed CD33-positive AML in adults and pediatric individuals aged ≥1 month OR relapsed/refractory CD33-positive AML in adults and pediatric individuals aged ≥2 yearsage thresholds per indication; CD33-positive

Follow label dosing and monitoring.

Padcev (enfortumab) MIBC neoadjuvant/adjuvant: Individual aged ≥18 AND ineligible for cisplatin-containing chemotherapy AND Padcev used in combination with pembrolizumab or pembrolizumab plus berahyaluronidase alfa-pmph as neoadjuvant therapy and continued as adjuvant after cystectomyage >=18; cisplatin-ineligible

See EV-303 neoadjuvant/adjuvant trial criteria.

Padcev (mUC) single-agent or combination: Adult individual with locally advanced or metastatic urothelial cancer who either (a) is cisplatin-ineligible and previously received ≥1 prior line of therapy OR (b) previously received a PD-1/PD-L1 inhibitor and platinum-containing chemotherapy; Padcev also covered in specified combinations with pembrolizumab ± berahyaluronidase alfaage >=18; prior therapy per selection

See EV-201 and combination cohorts.

Polivy (polatuzumab) DLBCL: In combination with a rituximab product + cyclophosphamide, doxorubicin, and prednisone (R-CHP) for previously untreated DLBCL or HGBL with IPI ≥2 OR in combination with bendamustine + rituximab for relapsed/refractory DLBCL or as bridging to anti-CD19 CAR-T therapyIPI >=2 for first-line use

Follow trial-derived dosing and label.

Tivdak (tisotumab) cervical cancer: Individual aged ≥18 AND recurrent or metastatic cervical cancer AND disease progression on or after prior chemotherapyage >=18

See innovaTV 204 trial eligibility and exclusions.

Zynlonta (loncastuximab) LBCL: Individual aged ≥18 AND relapsed or refractory large B-cell lymphoma (including DLBCL and HGBL) AND received ≥2 lines of systemic therapy>=2 prior systemic regimens; age >=18

See LOTIS-2 dosing and eligibility.

Coverage criteria added per 2025 update; follow specific criteria in policy for indication and prior therapies

per policy-specific criteria

Datroway added in 2025 update.

Document prior lines of systemic therapy and dates
Document prior specific agents when required by the drug criteria (eg, prior bevacizumab for Elahere)
Document tumor biomarker testing results and assay name when required (eg, FRα testing method for Elahere; MET assay for Emrelis)

Denial Risk

Biomarker and Exclusion‑based Denials

If required biomarker results or prior therapy documentation are absent or do not meet the drug‑specific criteria, the request will be denied. Examples include lack of FRα positivity for Elahere, lack of c‑MET overexpression confirmation for Emrelis, or not meeting prior‑line requirements for agents like Zynlonta or Datroway.

Denial risk when biomarker testing not provided or not performed with required assay
Denial risk when prior therapy counts or specific prior agents are not documented

Prior Authorization

Non‑Formulary Exception and Duration

Non‑formulary exception approvals for drugs listed in this policy may be granted for up to 12 months when criteria are met and documentation demonstrates clinical benefit. Shorter initial approvals (eg, up to 3 or 6 months) may apply for specific drugs or review types as noted in the policy.

Non‑formulary exception duration: up to 12 months when criteria met
Re‑authorization durations depend on the drug and documented continued benefit

Note

Member Benefit Verification and Contract Exclusions

Verify member benefits and applicable contract exclusions prior to authorization. Coverage is subject to the member’s benefit plan; some plans may limit coverage or exclude these services. This policy does not apply to Medicare Advantage — always check the member benefit booklet or contact member services.

Check member benefit booklet or contact member services
Policy does not apply to Medicare Advantage
Coverage subject to member plan limits and contract exclusions

Documentation Required

Required Clinical Documentation

Required clinical documentation must be supplied with the request and should include office visit notes with diagnosis, relevant history, physical exam, medication history, tumor staging or disease extent, prior therapy details, and objective evidence of response when requesting re‑authorization.

Office visit notes with diagnosis, relevant history, physical exam, medication history
Documentation of prior systemic therapies (agents, dates, responses)
Imaging or lab reports demonstrating disease status and response for re‑authorization requests

Documentation Required

Required Biomarker and Prior Therapy Documentation

When biomarker status or prior therapy is a criterion for approval, provide the test name, date, numeric/qualitative result, and laboratory performing the assay. For drugs with specific assay requirements (eg, VENTANA FOLR1 for FRα for Elahere; VENTANA MET (SP44) for Emrelis), indicate the assay used and results.

Provide assay name, date, result, and laboratory
For Elahere: evidence of FRα positivity and assay used (VENTANA FOLR1 RxDx)
For Emrelis: c‑MET overexpression results and assay used (eg, VENTANA MET SP44)

Documentation Required

Required Documentation Aligns with Prescribing Information

Documentation submitted should align with the FDA‑approved prescribing information for the requested product, including indication, dosing, and administration guidance. Exception approvals still require adherence to the product’s dosing and administration in the prescribing information.

Ensure requested dosing and schedule match FDA prescribing information
Non‑formulary approvals remain subject to FDA dosing/administration guidance

Note

Line‑of‑Therapy Sequencing

Follow the line‑of‑therapy sequencing and specific sequencing guidance within this policy and referenced guidelines. Many agents have approvals tied to number of prior systemic therapies (eg, Zynlonta and Datroway require 2 or more prior lines as specified).

Document number of prior lines and sequence of therapies when required
Ensure sequencing relative to transplant or CAR‑T eligibility is documented where relevant

Note

Sequencing Relative to Other Agents

Where the policy references use relative to other agents (for example Padcev after platinum chemotherapy and PD‑1/PD‑L1 inhibitor exposure, or Padcev combined with pembrolizumab regardless of cisplatin eligibility), include documentation of prior platinum and immunotherapy exposure and timing.

Document prior platinum chemotherapy and PD‑1/PD‑L1 inhibitor exposure for Padcev monotherapy or combinations
For Padcev combinations (with pembrolizumab ± berahyaluronidase alfa‑pmph), document prior therapies and indication for combination use

Note

Guideline‑Referenced Sequencing

Use guideline‑referenced sequencing and regimen recommendations (eg, NCCN tables) to support medical necessity when applicable. Cite relevant guideline recommendations in the clinical rationale when sequencing choices follow accepted guidelines.

When applicable, reference NCCN or other guideline regimen sequencing to support requests
Include rationale tying chosen regimen to guideline recommendations

Documentation Required

Regimen Sequencing — Padcev Combinations and Neoadjuvant/Adjuvant Use

For regimens that combine agents listed in this policy (for example Padcev with pembrolizumab or Padcev with pembrolizumab and berahyaluronidase alfa‑pmph, or neoadjuvant then adjuvant use around cystectomy for MIBC), document the intended regimen, treatment setting (neoadjuvant/adjuvant/advanced), prior therapies, and planned sequence of administration.

State whether regimen is neoadjuvant, adjuvant, or for metastatic disease
Document planned continuation after surgery when applicable (eg, neoadjuvant then adjuvant Padcev + pembrolizumab)
Provide rationale and supportive data if using combinations outlined in the policy

Follow-up noteMedian PFS follow-up time reported (Study 3: 22 months).

CR/CRi definition

CR/CRi definitionComplete remission (CR) plus complete remission with incomplete hematologic recovery (CRi) as pre-specified primary efficacy endpoint in INO-VATE ALL.

MeasurementAssessed per trial protocol (responses reported by cycle in INO-VATE ALL; used to determine efficacy and subsequent HSCT candidacy)

Results exampleIn INO-VATE ALL, overall CR/CRi rate with inotuzumab was 80.7% (ITT subgroup).

Objective Response Rate (ORR) definition

ORR definitionObjective response rate (ORR) is the proportion of individuals with a complete or partial response as assessed by independent review using tumor-specific criteria (e.g., RECIST v1.1 for solid tumors, Lugano 2014 for lymphoma).

Assessment examplesUsed as major efficacy outcome in Elahere (RECIST v1.1) and Tivdak (RECIST v1.1) and as primary efficacy measure in LOTIS-2 (Lugano 2014).

Reported valuesPolicy cites ORR examples: Tivdak confirmed ORR 24%; Zynlonta ORR 48.3%; Elahere ORR ~31.7% (study-reported).

Veno-occlusive disease (VOD) definition

VOD definitionVeno-occlusive disease (VOD), also called hepatic sinusoidal obstruction syndrome, observed after inotuzumab ozogamicin and reported up to 56 days from last dose; associated with increased post-HSCT mortality.

TimingSigns observed at mean 15 days (range 3-57 days) after last dose in INO-VATE ALL.

Clinical significanceVOD contributed to increased day-100 post-HSCT mortality and included fatal cases in trial experience.

Padcev combinations (definition/notation)

Padcev combination notationPadcev (enfortumab vedotin-ejfv) + pembrolizumab ± berahyaluronidase alfa-pmph — policy specifies use as neoadjuvant then adjuvant for MIBC and for locally advanced/metastatic urothelial cancer combinations.

Clinical settingNeoadjuvant then continued as adjuvant after cystectomy for cisplatin-ineligible adult MIBC patients; also covered for mUC in updated indications.

Policy updateCoverage criteria updated in 2026 to include these combinations per prescribing information reviews.

c-Met overexpression biomarker requirement

c-Met overexpression thresholdHigh c-Met protein overexpression is defined as ≥50% of tumor cells with strong (3+) staining by IHC.

Required assay contextPolicy references central testing and confirmation by VENTANA MET (SP44) RxDx Assay in clinical trials for Emrelis.

Indication linkageThis threshold is required for Emrelis (telisotuzumab vedotin) eligibility in locally advanced/metastatic non-squamous NSCLC.

HER2 / HR status biomarker requirement

HER2/HR status requirementFor Datroway in breast cancer: hormone receptor (HR)-positive and HER2-negative defined as IHC 0, IHC 1+, or IHC 2+/ISH-.

Age requirementIndicated for individuals aged 18 years or older for the breast cancer indication.

Therapy historyPrior endocrine-based therapy and chemotherapy for unresectable/metastatic disease required per policy criteria.

FRα (folate receptor alpha) biomarker requirement

FRα requirement (general)FRα (folate receptor alpha) positivity is required for Elahere in platinum-resistant epithelial ovarian, fallopian tube, or primary peritoneal cancer.

Prior therapy limitsElahere trial allowed up to three prior systemic therapies and required prior bevacizumab exposure.

ExclusionsTrial excluded individuals with corneal disorders, ongoing ocular treatment needs, Grade>1 peripheral neuropathy, or noninfectious interstitial lung disease.

FRα positive by VENTANA FOLR1 RxDx Assay

Assay requirementFRα positivity must be determined using the VENTANA FOLR1 (FOLR1-2.1) RxDx Assay as used in Study 0417 for Elahere eligibility.

Trial enrollmentStudy 0417 enrolled patients whose tumors were positive by this assay (n=106; efficacy evaluable n=104).

Testing implicationsDocumentation of assay results is expected for prior authorization per policy guidance.

c-Met protein overexpression by VENTANA MET (SP44) RxDx Assay

Assay and definitionHigh c-Met protein overexpression was confirmed by central testing and defined as ≥50% of tumor cells with strong (3+) membrane and/or cytoplasmic staining by the VENTANA MET (SP44) RxDx Assay.

Confirmation rateIn LUMINOSITY, retrospective testing with the VENTANA MET (SP44) assay confirmed high c-Met OE in 32/37 evaluable samples (87%).

Implication for coveragePolicy requires validated assay results for Emrelis eligibility consistent with trial definitions.

CD22 requirement (leukemic blasts >=70% by flow)

CD22 thresholdIn INO-VATE ALL, eligibility required ≥70% leukemic blasts expressing CD22 as determined by flow cytometry.

Dosing contextInotuzumab dosing in trial: 1.8 mg/m2 per cycle in a fractionated schedule (0.8 mg/m2 Day 1; 0.5 mg/m2 Days 8 and 15).

Clinical relevanceCD22 expression threshold was used to select patients and interpret high CR/CRi rates and subsequent HSCT candidacy.

FRα (per prescribing information)

FRα per prescribing informationElahere is indicated for FRα-positive, platinum-resistant epithelial ovarian, fallopian tube, or primary peritoneal cancer as defined in the prescribing information and trial (positive by validated assay).

Label-consistent testingPolicy and trial used VENTANA FOLR1 RxDx Assay to define FRα positivity; documentation should align with prescribing information.

Use limitationIndication applies to adults who meet prior therapy requirements per label (one to three prior regimens and prior bevacizumab in trial).

CD33 biomarker requirement

CD33 requirementGemtuzumab ozogamicin (Mylotarg) is indicated for CD33-positive AML; CD33 positivity identifies eligible AML populations per trials and guidelines.

Age-specific indicationsIndications include newly-diagnosed CD33-positive AML in adults and pediatric individuals aged ≥1 month, and relapsed/refractory CD33-positive AML in older pediatric groups per policy text.

Guideline alignmentNCCN therapy tables reference CD33-directed therapy options in AML; testing should be documented for coverage determinations.

FRα positive (alternate index)

Alternate FRα indexPolicy reiterates FRα-positive disease per prescribing information and trial (VENTANA FOLR1 assay) as the required biomarker for Elahere eligibility.

Therapy lineElahere applies in platinum-resistant disease after one or more prior systemic regimens as described in the label and policy.

Documentation noteAuthorization requires documented assay result and prior therapy history consistent with labeling.

c-Met high overexpression (alternate index)

c-Met high overexpression alternate indexHigh c-Met OE for Emrelis is defined in policy and trials as ≥50% tumor cells with strong (3+) staining; central testing and retrospective confirmation with VENTANA MET (SP44) supported this threshold.

Clinical trial confirmationIn LUMINOSITY, 87% of retested evaluable samples were confirmed as high c-Met OE using VENTANA MET (SP44).

Coverage implicationValidated assay results demonstrating the high overexpression threshold are required for coverage consideration.

EGFR mutation (for Datroway NSCLC indication)

EGFR mutation requirementDatroway has an indication for locally advanced or metastatic EGFR-mutated NSCLC and requires prior EGFR-directed therapy and platinum-based chemotherapy per policy criteria.

DosingRecommended dosing in trials/policy: 6 mg/kg IV every 3 weeks (maximum 540 mg).

EvidenceDatroway approvals and coverage criteria reference Phase III and pooled trial data in EGFR-mutated NSCLC populations.

Reviewed prescribing information; updated Padcev coverage to include combination with pembrolizumab regardless of cisplatin eligibility and revised Besponsa age requirement to include individuals 1 year of age and older.

2023policy_update

Reviewed prescribing information and updated Padcev coverage to include use in combination with pembrolizumab for cisplatin-ineligible adults with locally advanced or metastatic urothelial cancer.