Notification



Notification Issue Date:



Medical Policy Bulletin


Title:Brentuximab Vedotin (Adcetris®)

Policy #:08.01.13c

This policy is applicable to the Company’s commercial products only. Policies that are applicable to the Company’s Medicare Advantage products are accessible via a separate Medicare Advantage policy database.


The Company makes decisions on coverage based on Policy Bulletins, benefit plan documents, and the member’s medical history and condition. Benefits may vary based on contract, and individual member benefits must be verified. The Company determines medical necessity only if the benefit exists and no contract exclusions are applicable.

When services can be administered in various settings, the Company reserves the right to reimburse only those services that are furnished in the most appropriate and cost-effective setting that is appropriate to the member’s medical needs and condition. This decision is based on the member’s current medical condition and any required monitoring or additional services that may coincide with the delivery of this service.

This Medical Policy Bulletin document describes the status of medical technology at the time the document was developed. Since that time, new technology may have emerged or new medical literature may have been published. This Medical Policy Bulletin will be reviewed regularly and be updated as scientific and medical literature becomes available. For more information on how Medical Policy Bulletins are developed, go to the About This Site section of this Medical Policy Web site.



Policy

Coverage is subject to the terms, conditions, and limitations of the member's contract.

MEDICALLY NECESSARY

Brentuximab vedotin (Adcetris®) is considered medically necessary and, therefore, covered when used for any of the following indications:

CLASSICAL HODGKIN LYMPHOMA
  • The treatment of individuals with Classical Hodgkin lymphoma after failure of autologous hematopoietic stem cell transplant
  • The treatment of individuals with Classical Hodgkin lymphoma who are not autologous hematopoietic stem cell therapy candidates after failure of at least two prior multi-agent chemotherapy regimens
  • Individuals with Classical Hodgkin lymphoma at high risk of relapse or progression as post-auto- hematopoietic stem cell transplantation consolidation
    • Maintenance therapy following high-dose therapy and autologous stem cell rescue for refractory disease or relapse, or Deauville score 1-4 prior to transplant, in patients who have not received prior brentuximab vedotin (Adcetris®)
  • Single agent palliative therapy for relapsed or refractory disease in adults over 60 years of age

NON-HODGKIN LYMPHOMA
Peripheral T-cell Lymphoma
  • Preferred second-line or subsequent therapy for relapsed or refractory systemic anaplastic large cell lymphoma, CD30+ peripheral T-cell lymphoma, or CD30+ angioimmunoblastic T-cell lymphoma

Mycosis Fungoides (MF)/Sezary Syndrome (SS)
First-line chemotherapy for:
  • Stage IB-IIA MF with histologic evidence of folliculotropic or large cell transformation or stage IIB with generalized tumor lesions, with or without skin-directed therapy
  • Stage IV non-Sezary or visceral disease
  • Refractory or progressive stage III MF or SS

Anaplastic Large Cell Lymphoma
  • Preferred second-line or subsequent therapy for relapsed or refractory systemic anaplastic large cell lymphoma
  • The treatment of individuals with systemic anaplastic large cell lymphoma after failure of at least one prior multi-agent chemotherapy regimen
  • Single-agent therapy for primary cutaneous anaplastic large cell lymphoma (ALCL) with multifocal lesions or cutaneous ALCL with regional nodes (excludes systemic ALCL) as:
    • Primary treatment
    • Therapy for relapsed or refractory disease
  • Breast implant-associated ALCL- Adjuvant systemic therapy for localized disease to capsule/implant/breast following incomplete excision or partial capsulectomy with residual disease or for extended disease (stage II-IV)

Primary Cutaneous CD30+ T-cell Lymphoproliferative Disorders
  • Single agent therapy for symptomatic lymphomatoid papulosis (LyP) or LyP with extensive lesions if refractory to all primary treatment options

Adult T-cell Leukemia/Lymphoma
  • Preferred second line or subsequent therapy after high dose therapy/autologous stem cell rescue for CD30+ acute disease or lymphoma

EXPERIMENTAL/INVESTIGATIONAL

All other uses for brentuximab vedotin (Adcetris®) are considered experimental/investigational and, therefore, not covered unless the indication is supported as an accepted off-label use, as defined in the Company medical policy on off-label coverage for prescription drugs and biologics.

REQUIRED DOCUMENTATION

The individual's medical record must reflect the medical necessity for the care provided. These medical records may include, but are not limited to: records from the professional provider's office, hospital, nursing home, home health agencies, therapies, and test reports.

The Company may conduct reviews and audits of services to our members, regardless of the participation status of the provider. All documentation is to be available to the Company upon request. Failure to produce the requested information may result in a denial for the drug.
Guidelines

BLACK BOX WARNINGS

Refer to the specific manufacturer's prescribing information for any applicable Black Box Warnings.

BENEFIT APPLICATION

Subject to the terms and conditions of the applicable benefit contract, brentuximab vedotin (Adcetris®) is covered under the medical benefits of the Company’s products when the medical necessity criteria listed in this medical policy are met.

US FOOD AND DRUG ADMINISTRATION (FDA) STATUS

Brentuximab vedotin (Adcetris®) was approved by the FDA on August 19, 2011, for the treatment of individuals with the following indications:
  • Individuals with classical Hodgkin lymphoma after failure of autologous hematopoietic stem cell transplant
  • Individuals with classical Hodgkin lymphoma who are not candidates for autologous hematopoietic stem cell transplant and after failure of two prior multi-agent chemotherapy treatments
  • Individuals with classical Hodgkin lymphoma at high risk of relapse or progression as post auto- hematopoietic stem cell transplantation consolidation
  • Individuals with systemic anaplastic large cell lymphoma after failure of at least one prior multi-agent chemotherapy regimen

PET 5-POINT SCALE (DEAUVILLE CRITERIA)

The Deauville scale is a 5-point scoring system recommended internationally for staging and assessment of treatment response in Hodgkin's lymphoma and certain types of non-Hodgkin's lymphoma. Fluro-deoxy-glucose (FDG) is a radioactive compound used for imaging. The metabolism of FDG in the body can be seen on PET scans. Since cancer cells are more metabolically active and use more glucose, these cells light up on scans as abnormal activity. The Deauville scale is based on visual interpretation of FDG uptake. Reference organs are the mediastinum and liver.

Score
PET/CT scan result
1
No uptake
2
Uptake mediastinum
3
Uptake > mediastinum but liver
4
Uptake moderately higher than liver
5
Uptake markedly higher than liver and/or new lesions

Complete metabolic response: scores 1-3 with absence of FDG-avid bone marrow lesions

Partial response: Deauville score 4-5, provided that uptake is decreased compared to baseline and absence of structural progression development

Stable disease (no metabolic response): Deauville score 4-5 without significant change in FDG uptake from baseline

Progressive disease: Deauville score 4-5 with increasing intensity compared to baseline or any interim scan or new FDG-avid focus consistent with malignant lymphoma.

Description

Lymphoma is a general term for a group of cancers that originate in the lymphatic system. There are two major categories of lymphoma, Hodgkin lymphoma and non-Hodgkin lymphoma; both express CD30.

CLASSICAL HODGKIN LYMPHOMA

Classical Hodgkin lymphoma is a type of Hodgkin lymphoma characterized by an abnormal type of B lymphocyte called Reed Sternberg cells. It accounts for 90 to 95 percent of Hodgkin lymphoma. Brentuximab vedotin (Adcetris®) was approved by the Food and Drug Administration (FDA) on August 19, 2011, for the treatment of individuals with Hodgkin lymphoma after failure of autologous hematopoietic stem cell transplantation (HSCT) or after failure of at least two prior multi-agent chemotherapy treatments in individuals who are not candidates for autologous HSCT.

On August 17, 2015, the FDA-approved label was updated to allow brentuximab vedotin (Adcetris®) for the treatment of individuals with Classical Hodgkin lymphoma after failure of autologous HSCT or after failure of at least two prior multi-agent chemotherapy treatments in individuals who are not candidates for autologous HSCT.

Brentuximab vedotin (Adcetris®) is an antibody-drug conjugate designed to target tumor cells expressing CD30, a tumor necrosis factor (TNF) receptor. The antibody-drug conjugate binds with the CD30, and a small molecule chemotherapeutic agent (monomethyl auristatin [MMAE]) is released. The MMAE causes cell cycle arrest and cell death.

FDA approval for brentuximab vedotin (Adcetris®) was supported by a multi-center phase two trial involving 102 study participants with Hodgkin lymphoma who had received a median of five prior therapies, including autologous stem cell transplant. These participants received the recommended dose and schedule of brentuximab vedotin (Adcetris®), which is 1.8 mg/kg administered as an intravenous infusion over 30 minutes every 3 weeks for a maximum of 16 cycles. Results showed that 73 percent experienced complete or partial response rate after treatment.

On August 17, 2015 brentuximab vedotin (Adcetris®) was approved for the treatment of individuals with classical Hodgkin lymphoma at high risk of relapse or progression as post auto-hematopoietic stem cell transplantation consolidation, treatment given after the cancer has disappeared following the initial therapy. The efficacy of brentuximab vedotin (Adcetris®) in this population was studied in a randomized, double-blind, placebo-controlled clinical trial of 329 individuals. The brentuximab vedotin (Adcetris®) group received 1.8mg/kg intravenously over 30 minutes every 3 weeks for up to 16 cycles. The primary endpoint was progression-free survival determined by an independent review facility. High risk of relapse or progression was defined by status following first-line therapy: refractory, relapse within 12 months, or relapse at 12 months or later with extranodal disease. The brentuximab vedotin (Adcetris®) group had a statistically significant improvement in progression-free survival than the placebo group (42.9 median months vs. 24.1 median months).

SYSTEMIC ANAPLASTIC LARGE CELL LYMPHOMA

Anaplastic large cell lymphoma is a rare form of indolent (slow growing) non-Hodgkin lymphoma. It accounts for 1 in 50 cases of non-Hodgkin lymphoma and is more common in children and men. This cancer often affects the lymph nodes, skin, liver, lungs, and bone marrow. This disease can be systemic (occurring throughout the body) or cutaneous (occurring in or on the skin).

Systemic anaplastic large cell lymphoma is a type of T-cell non-Hodgkin lymphoma that expresses the CD30 antigen. It occurs in both nodal and extranodal locations. Conventional first-line combination chemotherapy regimens used to treat systemic anaplastic large cell lymphoma often result in long-term remissions and sometimes cures; however, there are limited therapeutic options for individuals with relapsed or refractory disease. First-line chemotherapy regimen includes CHOP (cyclophosphamide, hydroxydoxorubicin [doxorubicin], oncovin [Vincristine], prednisone).

Brentuximab vedotin (Adcetris®) was also approved by the FDA on August 19, 2011, for treatment of individuals with systemic anaplastic large cell lymphoma, a type of non-Hodgkin lymphoma, after failing at least one prior multi-agent chemotherapy regimen. The FDA approval of brentuximab vedotin (Adcetris®) for systemic anaplastic large cell lymphoma was based on a phase two open-label, single-arm, multi-center trial involving 58 individuals who experienced a relapse of systemic anaplastic large cell lymphoma after receiving a median of two prior therapies. Eighty-six percent of study participants experienced a complete or partial response rate after treatment with brentuximab vedotin (Adcetris®).

There may be additional indications contained in the Policy section of this document due to evaluation of criteria highlighted in the Company’s off-label policy, and/or review of clinical guidelines issued by leading professional organizations and government entities.
References


American Hospital Formulary Service (AHFS). Drug Information. 2017. Brentuximab vedotin. [LexiDrugs website]. 03/08/2017. Available at: http://online.lexi.com/lco/action/home[via subscription only]. Accessed September 25, 2017.

Elsevier Gold Standard’s Clinical Pharmacology Compendium. Brentuximab vedotin. [Clinical Pharmacology website]. 03/11/2016. Available at: http://www.clinicalpharmacology-ip.com/default.aspx. [via subscription only]. Accessed September 25, 2017.

Lexi-Drugs Compendium. Brentuximab vedotin (Adcetris®). 09/18/2017. [Lexicomp Online Web site]. Available at: http://online.lexi.com/lco/action/doc/retrieve/docid/patch_f/3509801 [via subscription only]. Accessed September 25, 2017.

Lymphoma Research Foundation [website]. Anaplastic Large Cell Lymphoma. Revised 08/2016. Available at: http://www.lymphoma.org/site/pp.asp?c=bkLTKaOQLmK8E&b=6300143. Accessed September 20, 2017.

Lymphoma Research Foundation [website]. Hodgkin Lymphoma. 2016. Available at: http://www.lymphoma.org/site/pp.asp?c=bkLTKaOQLmK8E&b=6300137. Accessed September 25, 2017.

Lymphoma Research Foundation [website]. Non-Hodgkin Lymphoma. 2016. Available at: http://www.lymphoma.org/site/apps/s/content.asp?c=bkLTKaOQLmK8E&b=6298135&ct=8763927. Accessed September 25, 2017.

Micromedex® Healthcare Series [Internet database]. Brentuximab vedotin. Greenwood Village, CO: Thomson Micromedex. 06/01/2017. Available at:
http://www.micromedexsolutions.com/micromedex2/librarian. Accessed September 25, 2017.

National Comprehensive Cancer Network (NCCN). NCCN Clinical Practice Guidelines in Oncology - Hodgkin Lymphomas. V1.2017. [NCCN Web site]. 03/01/2017. Available at: http://www.nccn.org/professionals/physician_gls/pdf/hodgkins.pdf [via subscription only]. Accessed September 25, 2017.

National Comprehensive Cancer Network (NCCN). NCCN Clinical Practice Guidelines in Oncology - T-Cell Lymphomas. V2.2017. [NCCN Web site]. 02/21/2017. Available at: http://www.nccn.org/professionals/physician_gls/PDF/nhl.pdf [via subscription only]. Accessed September 25, 2017.

National Comprehensive Cancer Network (NCCN). NCCN Drugs and Biologics Compendium. Brentuximab vedotin. [NCCN Web site]. Available at:
http://www.nccn.org/index.asp [via subscription only]. Accessed September 20, 2017.

Pro B, Advani R, Brice P, et al. Brentuximab vedotin (SGN-35) in patients with relapsed or refractorysystemic anaplastic large-cell lymphoma: Results of a phase II study. J Clin Oncol. 2012;30:2190-2196.

US Food and Drug Administration (FDA). Center for Drug Evaluation and Research. Drugs @FDA. Prescribing Information. Adecetris® (brentuximab vedotin).[FDA website]. 09/28/2016. Available at: https://www.accessdata.fda.gov/drugsatfda_docs/label/2016/125388s088lbl.pdf. Accessed September 20, 2017.





Coding

Inclusion of a code in this table does not imply reimbursement. Eligibility, benefits, limitations, exclusions, precertification/referral requirements, provider contracts, and Company policies apply.

The codes listed below are updated on a regular basis, in accordance with nationally accepted coding guidelines. Therefore, this policy applies to any and all future applicable coding changes, revisions, or updates.

In order to ensure optimal reimbursement, all health care services, devices, and pharmaceuticals should be reported using the billing codes and modifiers that most accurately represent the services rendered, unless otherwise directed by the Company.

The Coding Table lists any CPT, ICD-9, ICD-10, and HCPCS billing codes related only to the specific policy in which they appear.

CPT Procedure Code Number(s)

N/A


Professional and outpatient claims with a date of service on or before September 30, 2015, must be billed using ICD-9 codes. Professional and outpatient claims with a date of service on or after October 1, 2015, must be billed using ICD-10 codes.

Facility/Institutional inpatient claims with a date of discharge on or before September 30, 2015, must be billed with ICD-9 codes. Facility/Institutional inpatient claims with a date of discharge on or after October 1, 2015, must be billed with ICD-10 codes.


ICD - 10 Procedure Code Number(s)

N/A


Professional and outpatient claims with a date of service on or before September 30, 2015, must be billed using ICD-9 codes. Professional and outpatient claims with a date of service on or after October 1, 2015, must be billed using ICD-10 codes.

Facility/Institutional inpatient claims with a date of discharge on or before September 30, 2015, must be billed with ICD-9 codes. Facility/Institutional inpatient claims with a date of discharge on or after October 1, 2015, must be billed with ICD-10 codes.


ICD -10 Diagnosis Code Number(s)

See Attachment A


HCPCS Level II Code Number(s)

J9042 Injection, brentuximab vedotin, 1 mg




Revenue Code Number(s)

N/A

Coding and Billing Requirements


Cross References

Attachment A: Brentuximab Vedotin (Adcetris®)
Description: ICD CODES AND NARRATIVES




Policy History

08.01.13c
11/01/2017This version of the policy will become effective 11/01/2017.

This policy has been updated to be consistent with the US Food and Drug Administration (FDA) labeling and NCCN compendia.

Policy criteria was updated to include new recommendations from NCCN:
  • Criteria was updated for Classical Hodgkin Lymphoma
  • Criteria was updated for peripheral T-cell lymphoma
  • Criteria was updated for Mycosis Fungoides/Sezary Syndrome
  • Criteria was updated for Anaplastic Large Cell Lymphoma
  • Adult T-cell Leukemia/Lymphoma was added as a new indication

Added description of Deauville criteria.
Version Effective Date: 11/01/2017
Version Issued Date: 11/01/2017
Version Reissued Date: N/A

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