Commercial

Medical Policy

Notification

Brentuximab Vedotin (Adcetris®)

Notification Issue Date:

This version of the policy will become effective 12/30/2019.

This policy has been updated to communicate the coverage criteria for Brentuximab vedotin (Adcetris®) in accordance with the US Food and Drug Administration (FDA) prescribing information and the National Comprehensive Cancer Network (NCCN) Compendia. Revisions have been made to all conditions:

Classical Hodgkin lymphoma
B-Cell lymphomas
Peripheral T-cell lymphoma
Mycosis fungoides/Sezary syndrome
Anaplastic large cell lymphoma
Adult T-cell leukemia/lymphoma

Title:

Brentuximab Vedotin (Adcetris®)

Policy #:

08.01.13j

Policy

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.

MEDICALLY NECESSARY

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

B-CELL LYMPHOMAS

Diffuse Large B-Cell Lymphoma

As treatment for CD30+ disease as second-line and subsequent therapy if no intention to proceed to transplant for any of the following conditions:

For relapsed or refractory disease >12 months after completion of first-line therapy
For primary refractory disease (partial response, no response, or progression) or relapsed disease <12 months after completion of first-line therapy if no intention to proceed CAR T-cell therapy
As alternative systemic therapy (if not previously used) for relapsed/refractory disease if no intention to proceed to CAR T-cell therapy

High-Grade B-Cell Lymphomas

For the treatment of individuals as a second-line or subsequent therapy for CD30+ disease if no intention to proceed to transplant, for any of the following conditions:

For relapsed or refractory disease >12 months after completion of first-line therapy
For primary refractory disease (partial response, no response, or progression) or relapsed disease <12 months after completion of first-line therapy if no intention to proceed to Chimeric antigen receptor (CAR T)-cell therapy
As alternative systemic therapy (if not previously used) for relapsed/refractory disease if no intention to proceed to CAR T-cell therapy

B-Cell Lymphomas Post-Transplant Lymphoproliferative Disorders (PTLD)

As treatment for CD30+ monomorphic PTLD (T-cell type) as a component of brentuximab + CHP (cyclophosphamide, doxorubicin, prednisone) regimen

Second-line and subsequent therapy for the treatment of individuals with CD30+ monomorphic PTLD (B-cell type) if no intention to proceed to transplant for any of the following conditions:

For relapsed disease >12 months after completion of initial treatment with chemoimmunotherapy
For primary refractory disease (partial response, no response, or progression) or relapsed disease <12 months after completion of initial treatment with chemoimmunotherapy if no intention to proceed to CAR T-cell therapy
As alternative systemic therapy (if not previously used) for relapsed/refractory disease if no intention to proceed to CAR T-cell therapy

For the treatment of individuals with CD30+ monomorphic PTLD (B-cell type) as a component of brentuximab + CHP (cyclophosphamide, doxorubicin, prednisone) regimen

HIV-Related B-Cell Lymphomas

For the treatment of individuals as a second-line or subsequent therapy for of CD30+ HIV-related diffuse large B-cell lymphoma, primary effusion lymphoma, and HHV8-positive diffuse large B-cell lymphoma, not otherwise specified (NOS) if no intention to proceed to transplant for any of the following conditions:

For relapsed disease >12 months after completion of first-line therapy
For primary refractory disease (partial response, no response, or progression) or relapsed disease <12 months after completion of first-line therapy if no intention to proceed to CAR T-cell therapy
As alternative systemic therapy (if not previously used) for relapsed/refractory disease if no intention to proceed to CAR T-cell therapy

CLASSICAL HODGKIN LYMPHOMA

For individuals 18 to 60 years old with any of the following therapeutic approaches:

As a maintenance therapy following high-dose therapy and autologous stem cell rescue (HDT/ASCR) for relapsed or refractory disease for individuals with a high risk* of relapse if Deauville 1- 4 prior to transplant

*National Comprehensive Cancer Network (NCCN) Note: Individuals with two or more of the following risk factors are considered high risk: remission duration less than 1 year; extranodal involvement; PET+ response at the time of transplant; B-cell lymphoma symptoms; and/or >1 salvage/subsequent therapy regimen

As second-line or subsequent systemic therapy (if not previously used) for relapsed or refractory disease for any of the following:

As a single agent
In combination with bendamustine
In combination with nivolumab ICE (ifosfamide, carboplatin, etoposide)

Second-line or subsequent systemic therapy (if not previously used) for relapsed or refractory disease in combination with nivolumab for any of the following conditions:
- disease that has relapsed or progressed after HDT/ASCR ± brentuximab vedotin
- individuals with relapsed/refractory disease who are transplant-ineligible based on comorbidity or failure of second-line chemotherapy
- post-allogeneic transplant

Second-line systemic therapy for relapsed or refractory disease in combination with nivolumab
Subsequent systemic therapy (if not previously used) for relapsed or refractory disease (only if Deauville 4 or 5 following restaging with FDG-PET/CT) in combination with nivolumab
As primary treatment in combination with AVD (doxorubicin, vinblastine, dacarbazine) for stage III-IV disease (use with caution in individuals >60 y; contraindicated in those with neuropathy) (NCCN prefered regimen)

For individuals older than 60 years of age with either of the following therapeutic approaches:

As primary treatment as a component of brentuximab vedotin followed by AVD (doxorubicin, vinblastine, dacarbazine) regimen conditionally followed by brentuximab vedotin in responding individuals with complete or partial response for stage I--II unfavorable or stage III-IV disease
As primary treatment in combination with dacarbazine for stage I--II unfavorable or stage III-IV disease
As a single agent part of palliative therapy for relapsed or refractory disease

For individuals 18 years or younger with either of the following therapeutic approaches:

Primary treatment for high risk disease as a component of one of the following:

Bv-AVE-PC (brentuximab vedotin, doxorubicin, vincristine, etoposide, prednisone, cyclophosphamide) regimen (preferred)
AEPA (brentuximab vedotin, etoposide, prednisone, doxorubicin) regimen

Additional treatment for high risk disease as a component of CAPDAC (cyclophosphamide, brentuximab vedotin, prednisone, dacarbazine) regimen following primary treatment with AEPA regimen

Re-induction therapy in combination with ISRT for relapsed or refractory disease (only in highly favorable individuals*) in individuals heavily pretreated (with platinum or anthracycline-based chemotherapy) or if a decrease in cardiac function observed, in combination with any of the following:

bendamustine
nivolumab
gemcitabine

*(NCCN) Note: Recommended for those who may avoid ASCR: initial stage other than IIIB or IVB, no prior exposure to RT, duration of CR1 >1 year, absence of extranodal disease or B symptoms at relapse.

Re-induction therapy or subsequent therapy (if not previously used) for relapsed or refractory disease as a consideration in individuals heavily pretreated (with platinum or anthracycline-based chemotherapy) or if a decrease in cardiac function observed, in combination with any of the following:

bendamustine
nivolumab
gemcitabine

Maintenance therapy following high-dose therapy and autologous stem cell rescue (HDT/ASCR) for relapsed or refractory disease for select high-risk individuals*

*(NCCN) Note: Any individuals with progressive disease, refractory disease, or relapse within one year of the original diagnosis

NCCN preferred consolidation/additional therapy for Pediatric Aggressive Mature B-Cell Lymphomas - Primary Mediastinal Large B-Cell Lymphoma if partial response achieved after therapy for relapsed or refractory disease

in combination with nivolumab
in combination with pembrolizumab

Pediatric individuals two years and older with previously untreated high risk classical Hodgkin lymphoma (cHL), in combination with doxorubicin, vincristine, etoposide, prednisone, and cyclophosphamide

Previously Untreated Stage III or IV Classical Hodgkin Lymphoma

For the treatment of adult individuals in combination with AVD (doxorubicin, vinblastine, dacarbazine)

Classical Hodgkin Lymphoma Consolidation

For the treatment of adult individuals with classical Hodgkin lymphoma at high risk of relapse or progression as post-autologous hematopoietic stem cell transplantation (auto-HSCT) consolidation
For the treatment of adult individuals with classical Hodgkin lymphoma after failure of auto-HSCT or after failure of at least two prior multi-agent chemotherapy regimens in individuals who are not auto-HSCT candidates

Anaplastic Large Cell Lymphoma Lymphomas

For the treatment of adult individuals with previously untreated systemic anaplastic large cell lymphoma (sALCL) or other CD30-expressing peripheral T cell lymphomas (PTCL), including angioimmunoblastic T-cell lymphoma and PTCL not otherwise specified, in combination with cyclophosphamide, doxorubicin, and prednisone
For the treatment of adult individuals with systemic anaplastic large cell lymphoma (sALCL) after failure of at least one prior multi-agent chemotherapy regimen
For the treatment of adult individuals with primary cutaneous anaplastic large cell lymphoma (pcALCL) or CD30-expressing mycosis fungoides (MF) who have received prior systemic therapy

T-CELL LYMPHOMAS

Previously Untreated Systemic Anaplastic Large Cell Lymphoma (sALCL) or Other CD30-Expressing Peripheral T-Cell Lymphomas (PTCL), in Combination with Chemotherapy

For the treatment of adult individuals with previously untreated sALCL or other CD30-expressing PTCL, including angioimmunoblastic T-cell lymphoma and PTCL not otherwise specified, in combination with cyclophosphamide, doxorubicin, and prednisone

Systemic Anaplastic Large Cell Lymphoma (sALCL)

For the treatment of adult individuals with sALCL after the failure of at least one prior multi-agent chemotherapy regimen

Primary Cutaneous Anaplastic Large Cell Lymphoma (pcALCL) or CD30-Expressing Mycosis Fungoides (MF)

For the treatment of adult individuals with pcALCL or CD30-expressing MF who have received prior systemic therapy

PRIMARY CUTANEOUS LYMPHOMAS
Primary Cutaneous CD30+ T-Cell Lymphoproliferative Disorders

For the treatment of primary cutaneous anaplastic large cell lymphoma (ALCL) with multifocal lesions, or cutaneous ALCL with regional node (N1) (excludes systemic ALCL) as a single agent for one of the following:
- Primary treatment (NCCN preferred)
- Relapsed/refractory disease
For the treatment of cutaneous anaplastic large cell lymphoma (ALCL) with regional node (N1) (excludes systemic ALCL):
- As a component of brentuximab vedotin + CHP (cyclophosphamide, doxorubicin, prednisone) for one of the following:
  - Primary treatment (NCCN preferred)
  - Relapsed/refractory disease
Therapy for lymphomatoid papulosis (LyP) with extensive lesions as a single agent for relapsed/refractory disease following clinical trial, observation, retreatment with primary treatment, or treatment with an alternative regimen not used for primary treatment

Mycosis Fungoides (MF)/Sezary Syndrome (SS)

NCCN-preferred systemic therapy as a single agent primary treatment for one of the following:

Stage IB-IIA MF in combination with skin-directed therapy in selected cases**
Stage IIB MF with limited tumor lesions, with or without local radiation therapy
Stage IIB MF with generalized tumor lesions, with or without in combination with skin-directed therapy
Stage III MF, in combination with skin-directed therapy
Stage IVA1 or IVA2 SS in combination with skin-directed therapy
Stage IVA2 non Sezary or stage IVB visceral disease (solid organ), with or without radiation therapy for local control
generalized cutaneous or extracutaneous lesions with large cell transformation (LCT), in combination with systemic therapy

**(NCCN) Note: Systemic therapies should be considered for individuals with extensive skin involvement, higher skin disease burden, predominantly plaque disease, blood involvement, and/or inadequate response to skin-directed therapy

NCCN preferred systemic therapy as a single agent subsequent treatment for one of the following:

Stage IA MF refractory to multiple previous therapies, in combination with skin-directed therapy in selected cases**
Relapsed stage IB-IIA MF with a lower skin disease burden (eg, predominantly patch disease), in combination with skin-directed therapy in selected cases**
Stage IB-IIA MF with a higher skin disease burden (eg, predominantly plaque disease) that is relapsed or persistent with T1-T2 disease, with or without skin-directed therapy that is relapsed or persistent with T1-T2 disease, in combination with skin-directed therapy in selected cases**
Stage IB-IIA MF that is refractory to multiple previous therapies, in combination with skin-directed therapy
Relapsed stage IIB MF with T1-2 limited tumor lesions, in combination with skin-directed therapy in selected cases**
Relapsed stage IIB MF with T3 limited extent lesions, with or without local radiation therapy
Persistent stage IIB MF with T1-3 limited tumor lesions, with or without local radiation therapy
Stage IIB MF with limited tumor lesions that are refractory to multiple previous therapies, in combination with skin-directed therapy
Relapsed stage IIB MF with T1-2 generalized tumor lesions, in combination with skin-directed therapy in selected cases** refractory to multiple previous therapies
Relapsed stage IIB MF with T3 generalized tumor lesions, in combination with skin-directed therapy
Persistent stage IIB MF with T1-3 generalized tumor lesions, in combination with skin-directed therapy
Stage IIB MF with generalized tumor lesions that are refractory to multiple previous therapies, in combination with skin-directed therapy
Stage III MF relapsed or persistent in combination with or without skin-directed therapy
Stage III MF that is refractory to multiple previous therapies, in combination with skin-directed therapy
Stage IVA1 or IVA2 relapsed or persistent Sezary syndrome, in combination with skin-directed therapy
Stage IVA2 non-Sezary or stage IVB visceral relapsed or persistent disease (solid organ), with or without radiation therapy for local control
Limited cutaneous lesions with large cell transformation (LCT) that is refractory to multiple previous therapies, in combination with skin-directed therapy
Relapsed or persistent generalized cutaneous or extracutaneous lesions with LCT, in combination with skin-directed therapy

T-CELL LYMPHOMAS

Primary Cutaneous CD30+ T-Cell Lymphoproliferative Disorders

Therapy for primary cutaneous anaplastic large cell lymphoma (ALCL) with multifocal lesions, or cutaneous ALCL with regional node (N1) (excludes systemic ALCL), as a single agent for one the following:

Primary treatment (NCCN preferred)
Relapsed/refractory disease

Therapy for cutaneous anaplastic large cell lymphoma (ALCL) with regional node (N1) (excludes systemic ALCL) as a component of brentuximab vedotin + CHP (cyclophosphamide, doxorubicin, prednisone) for one of the following:

Primary treatment
Relapsed/refractory disease

Therapy for lymphomatoid papulosis (LyP) with extensive lesions as a single agent for relapsed/refractory disease following clinical trial, observation, retreatment with primary treatment, or treatment with alternative regimen not used for primary treatment

Hepatosplenic T-Cell Lymphoma

As a single agent for CD30+ refractory disease after two first-line therapy regimens (NCCN preferred)

Extranodal NK/T-Cell Lymphoma, Nasal Type

As a single agent for CD30+ relapsed/refractory disease following additional therapy with an alternate combination chemotherapy regimen (asparaginase-based) not previously used

Peripheral T-Cell Lymphomas

As first-line therapy as a component of brentuximab vedotin + CHP (cyclophosphamide, doxorubicin, prednisone) regimen (NCCN preferred therapy) for any of the following:
- CD30+ stage I--IV peripheral T-cell lymphoma not otherwise specified (PTCL-NOS)
- Angioimmunoblastic T-cell lymphoma (AITL)
- Enteropathy-associated T-cell lymphoma (EATL)
- Monomorphic epitheliotropic intestinal T-cell lymphoma (MEITL)
- Nodal peripheral T-cell lymphoma with TFH phenotype (PTCL, TFH)
- Follicular T-cell lymphoma (FTCL) as a component of brentuximab vedotin + CHP (cyclophosphamide, doxorubicin, prednisone)
- Stage III, IV ALK-positive anaplastic large cell lymphoma or stage I-IV ALK-negative ALCL as a component of brentuximab vedotin + CHP (cyclophosphamide, doxorubicin, prednisone)
- Stage I, II ALK-positive anaplastic large cell lymphoma (ALCL) as a component of brentuximab vedotin + CHP (cyclophosphamide, doxorubicin, prednisone) for six cycles+/- Involved-site radiation therapy (ISRT)
As second-line or initial palliative intent therapy and subsequent therapy (NCCN preferred) as a single agent for any of the following conditions:

Relapsed/refractory anaplastic large cell lymphoma CD30+ peripheral T-cell lymphoma (PTCL)
CD30+ angioimmunoblastic T-cell lymphoma (AITL)
Anaplastic large cell lymphoma (ALCL)

Adult T-Cell Leukemia/Lymphoma

As NCCN preferred second-line or subsequent therapy as a single agent for nonresponders to first-line therapy for acute or lymphoma subtypes (for CD30+ cases)

As a component of brentuximab vedotin + CHP (cyclophosphamide, doxorubicin, prednisone) regimen for CD30+ individuals (NCCN preferred):
- As chemotherapy in nonresponders to first-line therapy for chronic/smoldering subtype
- As first-line therapy for acute subtype
- As continued treatment in responders to first-line therapy for acute subtype
- First-line therapy for lymphoma subtype
- Continued treatment in responders to first-line therapy for lymphoma subtype

T-Cell Lymphomas --- Breast Implant-Associated Anaplastic Large Cell Lymphoma (ALCL)

As adjuvant systemic therapy for the localized disease to capsule/implant/breast following incomplete excision or partial capsulectomy with the residual disease if node-positive or radiation therapy is not feasible, or consider for extended disease (stage II-IV)
- As a single agent
- As a component of brentuximab vedotin + CHP (cyclophosphamide, doxorubicin, prednisone)
As a second-line and subsequent therapy for relapsed/refractory disease, as a single agent (NCCN preferred)

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.

MANDATES

PENNSYLVANIA MEMBERS

In accordance with the Commonwealth of Pennsylvania's Act 6 of 2020 or Fair Access to Cancer Treatment Act, for members who are enrolled in Pennsylvania commercial products who have Stage 4, advanced metastatic cancer, refer to the Medical Policy titled "Coverage of Anticancer Prescription Oral and Injectable Drugs and Biologics and Supportive agents (08.01.08) for additional information regarding the applicable coverage of 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 lymphoma and certain types of non-Hodgkin 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.

INTERNATIONAL PROGNOSTIC SCORE (IPS) IN HODGKIN LYMPHOMA

Points	Criteria
1	Serum Albumin <4 g/dL
1	Hemoglobin <10.5 g/dL
1	Male Sex
1	Stage IV Disease by Ann Arbor Classification
1	Age ≥45 Years
1	White Cell Count ≥15,000/mm3
1	Lymphocyte Count <600/mm3 or <8% of White Cell Count

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 lymphocytes 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 classical 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 1.8 mg/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).

On March 20, 2018, brentuximab vedotin (Adcetris®) was approved for the treatment of individuals with previously untreated stage III or IV classical Hodgkin lymphoma in combination with chemotherapy. The approval for adult individuals with previously untreated stage III or IV classical Hodgkin lymphoma was based on a clinical trial comparing brentuximab vedotin Adcetris® plus chemotherapy, AVD regimen (Adriamycin [doxorubicin], vinblastine and dacarbazine) to a chemotherapy-only regimen common for classical Hodgkin lymphoma treatment (AVD plus bleomycin, also known as ABVD). The trial measured modified progression-free survival (mPFS), which considers the length of time it took for the disease to progress, death to occur, or new therapy to be initiated in individuals who did not achieve a complete response. In the trial of 1,334 individuals, after individuals received an average of six 28-day cycles of treatment, those treated with brentuximab vedotin Adcetris® plus AVD were 23 percent less likely to experience progression, death, or initiation of new therapy compared with those receiving ABVD. There were 117 individuals (18 percent) on the brentuximab vedotin Adcetris® plus AVD arm who experienced disease progression, death, or began new therapy compared to 146 (22 percent) individuals on the ABVD arm.

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. 2023. Brentuximab vedotin. [LexiDrugs website]. 04/21/2023. Available at: http://online.lexi.com/lco/action/home[via subscription only]. Accessed November 15, 2023.

Brentuximab vedotin (Adcetris®) [prescribing information]. Bothell, WA: Seagen Inc.; 06/2023. Available online at: ADCETRIS® (brentuximab vedotin) Healthcare Professional Site (adcetrispro.com). Accessed October 16, 2023.

Elsevier Gold Standard’s Clinical Pharmacology Compendium. Brentuximab vedotin. [Clinical Pharmacology website]. 11/22/2022. Available at: http://www.clinicalpharmacology-ip.com/default.aspx. [via subscription only]. Accessed November 15, 2023.

Lexi-Drugs Compendium. Brentuximab vedotin (Adcetris®). 11/15/2023. [Lexicomp Online Website]. Available at: http://online.lexi.com/lco/action/doc/retrieve/docid/patch_f/3509801 [via subscription only]. Accessed November 15, 2023.

Lymphoma Research Foundation [website]. Anaplastic Large Cell Lymphoma. Revised 2021. Available at: http://www.lymphoma.org/site/pp.asp?c=bkLTKaOQLmK8E&b=6300143. Accessed November 15, 2023.

Lymphoma Research Foundation [website]. Hodgkin Lymphoma. 2021. Available at: http://www.lymphoma.org/site/pp.asp?c=bkLTKaOQLmK8E&b=6300137. Accessed November 15, 2023.

Lymphoma Research Foundation [website]. Non-Hodgkin Lymphoma. 2021. Available at: http://www.lymphoma.org/site/apps/s/content.asp?c=bkLTKaOQLmK8E&b=6298135&ct=8763927. Accessed November 15, 2023.

Micromedex® Healthcare Series [Internet database]. Brentuximab vedotin. Greenwood Village, CO: Thomson Micromedex. 11/14/2023. Available at:
http://www.micromedexsolutions.com/micromedex2/librarian. Accessed November 15, 2023.

National Comprehensive Cancer Network (NCCN). NCCN Clinical Practice Guidelines in Oncology - Pediatric Hodgkin Lymphomas. V2.2023. [NCCN Web site]. 03/09/2023. Available at: http://www.nccn.org/professionals/physician_gls/pdf/hodgkins.pdf [via subscription only]. Accessed November 15, 2023.

National Comprehensive Cancer Network (NCCN). NCCN Clinical Practice Guidelines in Oncology - Hodgkin Lymphomas. V1.2024. [NCCN Web site]. 10/12/2023. Available at: http://www.nccn.org/professionals/physician_gls/pdf/hodgkins.pdf [via subscription only]. Accessed November 15, 2023.

National Comprehensive Cancer Network (NCCN). NCCN Clinical Practice Guidelines in Oncology - T-Cell Lymphomas. V1.2023. [NCCN Web site]. 01/05/2023. Available at: http://www.nccn.org/professionals/physician_gls/PDF/nhl.pdf [via subscription only]. Accessed November 15, 2023.

National Comprehensive Cancer Network (NCCN). NCCN Clinical Practice Guidelines in Oncology - Primary Cutaneous Lymphomas. V1.2023. [NCCN Web site]. 01/05/2023. Available at: http://www.nccn.org/professionals/physician_gls/PDF/nhl.pdf [via subscription only]. Accessed November 15, 2023.

National Comprehensive Cancer Network (NCCN). NCCN Clinical Practice Guidelines in Oncology - B-Cell Lymphomas. V6.2023. [NCCN Web site]. 10/10/2023. Available at: http://www.nccn.org/professionals/physician_gls/PDF/nhl.pdf [via subscription only]. Accessed November 15, 2023.

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 November 15, 2023.

Pro B, Advani R, Brice P, et al. Brentuximab vedotin (SGN-35) in patients with relapsed or refractory systemic 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]. 06/14/2023. Available at: https://www.accessdata.fda.gov/drugsatfda_docs/label/2016/125388s088lbl.pdf. Accessed November 15, 2023.

Coding

CPT Procedure Code Number(s)

N/A

ICD - 10 Procedure Code Number(s)

N/A

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

MPMiscCodesNarrativesPub

Coding and Billing Requirements

Cross Reference

Policy History

Version Effective Date:

10/1/2024

Version Issued Date:

10/1/2024

Version Reissued Date: