Medicare Advantage

Medical Policy

Notification

Brentuximab Vedotin (Adcetris®)

Notification Issued 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 #:

MA08.068k

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 Chimeric antigen recreptor (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 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)

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

HIV-Related B-Cell Lymphomas

For the treatment of individuals as a second-line or subsequent therapy for of CD30+ human immunodeficiency virus (HIV)-related diffuse large B-cell lymphoma, primary effusion lymphoma, and human herpesvirus-8 (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

Pediatric Aggressive Mature B-Cell Lymphomas

National Comprehensive Cancer Network (NCCN)-preferred consolidation/additional therapy for pediatric aggressive mature B-cell lymphomas for primary mediastinal large B-cell lymphoma if partial response achieved after therapy for relapsed or refractory disease

in combination with nivolumab (Opdivo)
in combination with pembrolizumab (Keytruda)

CLASSIC 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 score is 1 to 4 prior to transplant

*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 for relapsed or refractory disease for any of the following:

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

As primary treatment in combination with AVD (doxorubicin, vinblastine, dacarbazine) for stage III to IV disease (use with caution in individuals >60 years old; contraindicated in those with neuropathy) (NCCN-prefered regimen)
As primary treatment in combination as a component of BrECADD (brentuximab vedotin, etoposide, cyclophosphamide, doxorubicin, dacarbazine, dexamethasone) for stage III to IV disease

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 to II unfavorable or stage III to IV disease
As primary treatment in combination with dacarbazine with low ejection fraction
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

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

Previously Untreated Stage III or IV Classic Hodgkin Lymphoma

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

Classic Hodgkin Lymphoma Consolidation

For the treatment of adult individuals with classic 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 classic 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

T-CELL LYMPHOMAS

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 (CHP)
For the treatment of adult individuals with 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

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)
- Stage III, IV ALK-positive ALCL or stage I-IV ALK-negative ALCL (NCCN preferred therapy)
- Stage I, II ALK-positive ALCL as a component of brentuximab vedotin + CHP (cyclophosphamide, doxorubicin, prednisone) for six cycles+/- Involved-site radiation therapy (ISRT) (NCCN preferred therapy)
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 ALCL CD30+ peripheral T-cell lymphoma (PTCL)
CD30+ angioimmunoblastic T-cell lymphoma (AITL)
ALCL
sALCL after failure of at least one prior multiagent chemotherapy regimen

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

As NCCN-preferred 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 RT 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)

Adult T-Cell Leukemia/Lymphoma

As NCCN-preferred second-line or subsequent therapy as a single agent for nonresponders to first-line therapy for chronic high risk, acute or lymphoma subtypes (for CD30+ cases)
As a component of brentuximab vedotin + CHP (cyclophosphamide, doxorubicin, prednisone) regimen for CD30+ individuals (NCCN preferred):
- As additional therapy in nonresponders to first-line therapy for chronic low risk/smoldering symptomatic subtype
- First-line therapy for chronic high-risk subtype
- As additional therapy in nonresponders to first-line therapy with zidovudine and interferon for chronic high-risk subtype
- As first-line therapy for acute subtype
- As continued treatment in responders to first-line therapy for acute subtype
- As additional therapy in nonresponders to first-line therapy for acute subtype (if not used in first-line therapy)
- First-line therapy for lymphoma subtype
- Continued treatment in responders to first-line therapy for lymphoma subtype

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

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

For the treatment of primary cutaneous 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 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
For the treatment of adult individuals with primary cutaneous pcALCL or CD30-expressing mycosis fungoides (MF) who have received prior systemic therapy

Mycosis Fungoides (MF)/Sézary 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 RT
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-Sézary or stage IVB visceral disease (solid organ), with or without RT 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

Systemic therapy in combination with bendamustine as primary treatment for one of the following:

Stage IVA2 non-Sézary or stage IVB visceral disease (solid organ), with or without RT for local control
Generalized cutaneous or extracutaneous lesions with LCT, in combination with skin-directed therapy (NCCN-preferred)

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 I–IIA MF with a lower skin disease burden (e.g., predominantly patch disease), in combination with skin-directed therapy in selected cases**
Stage IB-IIA MF with a higher skin disease burden (e.g., 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 RT
Persistent stage IIB MF with T1–3 limited tumor lesions, with or without local RT
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 Sézary syndrome, in combination with skin-directed therapy
Stage IVA2 non-Sézary or stage IVB visceral relapsed or persistent disease (solid organ), with or without RT for local control
Limited cutaneous lesions with 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

Systemic therapy in combination with bendamustine as subsequent treatment for one of the following:

Stage IIB mycosis fungoides (MF) with generalized tumor lesions that is refractory to multiple previous therapies, in combination with skin-directed therapy (NCCN-preferred)
Stage III MF that is refractory to multiple previous therapies, in combination with skin-directed therapy (NCCN-preferred)
Relapsed or persistent stage IVA2 non-Sézary or stage IVB visceral disease (solid organ), with or without RT for local control
Limited cutaneous lesions with LCT that is refractory to multiple previous therapies, in combination with skin-directed therapy (NCCN-preferred)
Relapsed or persistent LCT with generalized cutaneous or extracutaneous lesions, in combination with skin-directed therapy (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.

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

There is no Medicare coverage determination addressing this drug; therefore, the Company policy is applicable.

BENEFIT APPLICATION

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

Certain drugs are available through either the member's medical benefit (Part B benefit) or pharmacy benefit (Part D benefit), depending on how the drug is prescribed, dispensed, or administered. This medical policy only addresses instances when brentuximab vedotin (Adcetris) is covered under a member's medical benefit (Part B benefit). It does not address instances when brentuximab vedotin (Adcetris) is covered under a member’s pharmacy benefit (Part D benefit).

BLACK BOX WARNINGS

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

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 classic Hodgkin lymphoma after failure of autologous hematopoietic stem cell transplant
Individuals with classic Hodgkin lymphoma who are not candidates for autologous hematopoietic stem cell transplant and after failure of two prior multiagent chemotherapy treatments
Individuals with classic Hodgkin lymphoma at high risk of relapse or progression as post autohematopoietic stem cell transplantation consolidation
Individuals with systemic anaplastic large cell lymphoma after failure of at least one prior multiagent chemotherapy regimen

Supplemental approvals for brentuximab vedotin (Adcetris) have since been issued by the FDA.

PET FIVE-POINT SCALE (DEAUVILLE CRITERIA)

The Deauville scale is a Five-point scoring system recommended internationally for staging and assessment of treatment response in Hodgkin lymphoma and certain types of non-Hodgkin lymphoma. Fluorodeoxyglucose (FDG) is a radioactive compound used for imaging. The metabolism of FDG in the body can be seen on PET scans. Because 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.

CLASSIC HODGKIN LYMPHOMA

Classic Hodgkin lymphoma (cHL) 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 US 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 multiagent 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 cHL after failure of autologous HSCT or after failure of at least two prior multiagent 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 multicenter 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 after treatment.

On August 17, 2015, brentuximab vedotin (Adcetris) was approved for the treatment of individuals with cHL 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 cHL in combination with chemotherapy. The approval for adult individuals with previously untreated stage III or IV cHL was based on a clinical trial comparing Adcetris plus chemotherapy, AVD regimen (Adriamycin [doxorubicin], vinblastine and dacarbazine) to a chemotherapy-only regimen common for cHL 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 1334 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 (18 percent) individuals 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 one 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 multiagent 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]. 03/11/2024. Available at: http://online.lexi.com/lco/action/home[via subscription only]. Accessed September 12, 2024.

Brentuximab vedotin (Adcetris®) [prescribing information]. Bothell, WA: Seagen Inc.; 06/2023. Available online at: ADCETRIS® (brentuximab vedotin) Healthcare Professional Site (adcetrispro.com). Accessed September 12, 2024.

Elsevier Gold Standard’s Clinical Pharmacology Compendium. Brentuximab vedotin. [Clinical Pharmacology website]. 09/11/2024. Available at: http://www.clinicalpharmacology-ip.com/default.aspx. [via subscription only]. Accessed September 12, 2024.

Lexi-Drugs Compendium. Brentuximab vedotin (Adcetris®). 08/22/2024. [Lexicomp Online Website]. Available at: http://online.lexi.com/lco/action/doc/retrieve/docid/patch_f/3509801 [via subscription only]. Accessed September 12, 2024.

Lymphoma Research Foundation [website]. Anaplastic Large Cell Lymphoma. Revised 2021. Available at: http://www.lymphoma.org/site/pp.asp?c=bkLTKaOQLmK8E&b=6300143. Accessed September 12, 2024.

Lymphoma Research Foundation [website]. Hodgkin Lymphoma. 2021. Available at: http://www.lymphoma.org/site/pp.asp?c=bkLTKaOQLmK8E&b=6300137. Accessed September 12, 2024.

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 September 12, 2024.

Micromedex® Healthcare Series [Internet database]. Brentuximab vedotin. Greenwood Village, CO: Thomson Micromedex. 09/17/2024. Available at:
http://www.micromedexsolutions.com/micromedex2/librarian. Accessed September 12, 2024.

National Comprehensive Cancer Network (NCCN). NCCN Clinical Practice Guidelines in Oncology - Pediatric Hodgkin Lymphomas. V1.2024. [NCCN Web site]. 05/14/2024. Available at: http://www.nccn.org/professionals/physician_gls/pdf/hodgkins.pdf [via subscription only]. Accessed September 12, 2024.

National Comprehensive Cancer Network (NCCN). NCCN Clinical Practice Guidelines in Oncology - Hodgkin Lymphomas. V3.2024. [NCCN Web site]. 03/18/2024. Available at: http://www.nccn.org/professionals/physician_gls/pdf/hodgkins.pdf [via subscription only]. Accessed September 12, 2024.

National Comprehensive Cancer Network (NCCN). NCCN Clinical Practice Guidelines in Oncology - T-Cell Lymphomas. V4.2024. [NCCN Web site]. 05/28/2024. Available at: http://www.nccn.org/professionals/physician_gls/PDF/nhl.pdf [via subscription only]. Accessed September 12, 2024.

National Comprehensive Cancer Network (NCCN). NCCN Clinical Practice Guidelines in Oncology - Primary Cutaneous Lymphomas. V3.2024. [NCCN Web site]. 08/22/2024. Available at: http://www.nccn.org/professionals/physician_gls/PDF/nhl.pdf [via subscription only]. Accessed September 12, 2024.

National Comprehensive Cancer Network (NCCN). NCCN Clinical Practice Guidelines in Oncology - B-Cell Lymphomas. V3.2024. [NCCN Web site]. 08/26/2024. Available at: http://www.nccn.org/professionals/physician_gls/PDF/nhl.pdf [via subscription only]. Accessed September 12, 2024.

National Comprehensive Cancer Network (NCCN). NCCN Clinical Practice Guidelines in Oncology - Pediatric Aggressive Mature B-Cell Lymphomas. V2.2024. [NCCN Web site]. 09/03/2024. Available at: http://www.nccn.org/professionals/physician_gls/PDF/nhl.pdf [via subscription only]. Accessed September 12, 2024.

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 12, 2024.

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. Adcetris® (brentuximab vedotin).[FDA website]. 06/14/2023. Available at: https://www.accessdata.fda.gov/drugsatfda_docs/label/2016/125388s088lbl.pdf. Accessed September 12, 2024.

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

Revisions From MA08.068k:

11/18/2024

This version of the policy will become effective 11/18/2024.

This policy has been updated to communicate the coverage criteria for brentuximab vedotin (Adcetris®) in accordance with the National Comprehensive Cancer Network (NCCN) Compendia. Revisions have been made to all of the following conditions:

Classic Hodgkin lymphoma
B-cell lymphomas
Primary cutaneous lymphomas
T-cell lymphomas

Revisions From MA08.068j:

10/01/2024

This policy has been identified for the ICD-10 code update, effective 10/01/2024.

The following ICD-10 code has been added to this policy:

C83.398 Diffuse large B-cell lymphoma of other extranodal and solid organ sites

C86.00 Extranodal NK/T-cell lymphoma, nasal type not having achieved remission

C86.10 Hepatosplenic T-cell lymphoma not having achieved remission

C86.20 Enteropathy-type (intestinal) T-cell lymphoma not having achieved remission

C86.50 Angioimmunoblastic T-cell lymphoma not having achieved remission

C86.60 Primary cutaneous CD30-positive T-cell proliferations not having achieved remission

The following ICD-10 code have been deleted from this policy:

C83.39 Diffuse large B-cell lymphoma, extranodal and solid organ sites

C86.0 Extranodal NK/T-cell lymphoma, nasal type

C86.1 Hepatosplenic T-cell lymphoma

C86.2 Enteropathy-type (intestinal) T-cell lymphoma

C86.5 Angioimmunoblastic T-cell lymphoma

C86.6 Primary cutaneous CD30-positive T-cell proliferations

Revisions From MA08.068i:

01/02/2024

This version of the policy will become effective 01/02/2024

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

Classical Hodgkin lymphoma
B-Cell lymphomas
Peripheral T-cell lymphoma
Mycosis fungoides/Sezary syndrome
Anaplastic large cell lymphoma
Adult T-cell leukemia/lymphoma
Follicular Lymphoma
T-Cell lymphomas
HIV-Related B-Cell Lymphomas

The following ICD-10 codes were added to the policy:
C81.90 - C81.99
C83.80 - C83.99
C84.90 - C84.99
C84.Z0 - C84.Z9
C85.20 - C85.29
C85.80 - C85.89

C82.00 - C82.29

C82.30 - C82.39
C82.40 - C82.49
C82.50 - C82.59
C82.60 - C82.69
C82.80 - C82.89

Revisions From MA08.068h:

01/01/2024	Effective 01/01/2024 this policy applies to New Jersey Medicare Advantage (MA) lines of business.
10/01/2022	This policy has been identified for the ICD-10 code update, effective 10/01/2022. The following ICD-10 code has been revised in this policy: FROM: C84.40 Peripheral T-cell lymphoma, not classified, unspecified site C84.41 Peripheral T-cell lymphoma, not classified, lymph nodes of head, face, and neck C84.42 Peripheral T-cell lymphoma, not classified, intrathoracic lymph nodes C84.43 Peripheral T-cell lymphoma, not classified, intra-abdominal lymph nodes C84.44 Peripheral T-cell lymphoma, not classified, lymph nodes of axilla and upper limb C84.45 Peripheral T-cell lymphoma, not classified, lymph nodes of inguinal region and lower limb C84.46 Peripheral T-cell lymphoma, not classified, intrapelvic lymph nodes C84.47 Peripheral T-cell lymphoma, not classified, spleen C84.48 Peripheral T-cell lymphoma, not classified, lymph nodes of multiple sites C84.49 Peripheral T-cell lymphoma, not classified, extranodal and solid organ sites TO: C81.40 Lymphocyte-rich Hodgkin lymphoma, unspecified site C81.41 Lymphocyte-rich Hodgkin lymphoma, lymph nodes of head, face, and neck C81.42 Lymphocyte-rich Hodgkin lymphoma, intrathoracic lymph nodes C81.43 Lymphocyte-rich Hodgkin lymphoma, intra-abdominal lymph nodes C81.44 Lymphocyte-rich Hodgkin lymphoma, lymph nodes of axilla and upper limb C81.45 Lymphocyte-rich Hodgkin lymphoma, lymph nodes of inguinal region and lower limb C81.46 Lymphocyte-rich Hodgkin lymphoma, intrapelvic lymph nodes C81.47 Lymphocyte-rich Hodgkin lymphoma, spleen C81.48 Lymphocyte-rich Hodgkin lymphoma, lymph nodes of multiple sites C81.49 Lymphocyte-rich Hodgkin lymphoma, extranodal and solid organ sites

01/01/2024

Effective 01/01/2024 this policy applies to New Jersey Medicare Advantage (MA) lines of business.

10/01/2022

This policy has been identified for the ICD-10 code update, effective 10/01/2022.

The following ICD-10 code has been revised in this policy:

FROM:

C84.40 Peripheral T-cell lymphoma, not classified, unspecified site

C84.41 Peripheral T-cell lymphoma, not classified, lymph nodes of head, face, and neck

C84.42 Peripheral T-cell lymphoma, not classified, intrathoracic lymph nodes

C84.43 Peripheral T-cell lymphoma, not classified, intra-abdominal lymph nodes

C84.44 Peripheral T-cell lymphoma, not classified, lymph nodes of axilla and upper limb

C84.45 Peripheral T-cell lymphoma, not classified, lymph nodes of inguinal region and lower limb

C84.46 Peripheral T-cell lymphoma, not classified, intrapelvic lymph nodes

C84.47 Peripheral T-cell lymphoma, not classified, spleen

C84.48 Peripheral T-cell lymphoma, not classified, lymph nodes of multiple sites

C84.49 Peripheral T-cell lymphoma, not classified, extranodal and solid organ sites

TO:

C81.40 Lymphocyte-rich Hodgkin lymphoma, unspecified site

C81.41 Lymphocyte-rich Hodgkin lymphoma, lymph nodes of head, face, and neck

C81.42 Lymphocyte-rich Hodgkin lymphoma, intrathoracic lymph nodes

C81.43 Lymphocyte-rich Hodgkin lymphoma, intra-abdominal lymph nodes

C81.44 Lymphocyte-rich Hodgkin lymphoma, lymph nodes of axilla and upper limb

C81.45 Lymphocyte-rich Hodgkin lymphoma, lymph nodes of inguinal region and lower limb

C81.46 Lymphocyte-rich Hodgkin lymphoma, intrapelvic lymph nodes

C81.47 Lymphocyte-rich Hodgkin lymphoma, spleen

C81.48 Lymphocyte-rich Hodgkin lymphoma, lymph nodes of multiple sites

C81.49 Lymphocyte-rich Hodgkin lymphoma, extranodal and solid organ sites

Revisions From MA08.068g:

06/20/2022

This version of the policy will become effective 06/20/2022

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

The following ICD-10 codes were added to the policy:
C83.50-Lymphoblastic (diffuse) lymphoma (unspecified site)
C83.51 Lymphoblastic (diffuse) lymphoma, head, face & neck
C83.52 Lymphoblastic (diffuse) lymphoma intrathoracic lymph nodes
C83.53 Lymphoblastic (diffuse) lymphoma intra-abdominal lymph nodes
C83.54 Lymphoblastic (diffuse) lymphoma axilla and upper limb
C83.55 Lymphoblastic (diffuse) lymphoma inguinal region and lower limb
C83.56 Lymphoblastic (diffuse) lymphoma intra pelvic
C83.57 Lymphoblastic (diffuse) lymphoma spleen
C83.58 Lymphoblastic (diffuse) lymphoma multiple sites
C83.59 Lymphoblastic (diffuse) lymphoma solid organ sites

C86.2 Enteropathy-type (intestinal) T-cell lymphoma

C86.4 Blastic NK-cell lymphoma

D47.Z7 -Other specified neoplasms of uncertain behavior of lymphoid, hematopoietic and related tissue

Revisions From MA08.068f:

10/01/2021

This policy has been identified for the ICD-10 code update, effective 10/01/2021.

The following ICD-10 code has been added to this policy:

C84.7A Anaplastic large cell lymphoma, ALK-negative, breast

Revisions From MA08.068e:

03/01/2021

This version of the policy will become effective 03/01/2021

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

The following codes were added to the policy:

C82.80, C82.81, C82.82, C82.83, C82.84, C82.85, C82.86, C82.87, C82.88, C82.89, C82.90, C82.91, C82.92, C82.93, C82.94, C82.95, C82.96, C82.97, C82.98, C82.99, C83.30, C83.3, C83.32, C83.33, C83.34, C83.35, C83.36, C83.37, C83.38, C83.39.

Revisions From MA08.068d:

12/30/2019

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

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

Revisions From MA08.068c:

11/01/2017

This 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

Revisions From MA08.068b:

10/01/2016

The following ICD-10 narratives have been revised in this policy:

C81.10 C81.11 C81.12 C81.13 C81.14 C81.15 C81.16 C81.17 C81.18 C81.19 C81.20 C81.21 C81.22 C81.23, C81.24 C81.25 C81.26 C81.27 C81.28 C81.29 C81.30 C81.31 C81.32 C81.33 C81.34 C81.35 C81.36 C81.37, C81.38 C81.39 C81.40 C81.41 C81.42 C81.43 C81.44 C81.45 C81.46 C81.47 C81.48 C81.49 C81.70 C81.71, C81.72 C81.73 C81.74 C81.75 C81.76 C81.77 C81.78 C81.79

Revisions From MA08.068a:

03/23/2016

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

Mycosis Fungoides/Sezary Syndrome was added as a new indication
Primary Cutaneous CD30+ T-cell Lymphoproliferative Disorders was added as a new indication
Peripheral T-cell was added as a new indication
Criteria was updated for Classical Hodgkin Lymphoma
Criteria was updated for Anaplastic Large Cell Lymphoma

The following codes were removed from the policy:
C81.00 C81.01 C81.02 C81.03 C81.04 C81.05 C81.06 C81.07 C81.08 C81.09 C81.90 HC81.91 C81.92 C81.93 C81.94 C81.95 C81.96 C81.97 C81.98 C81.99 Z85.71 Z85.72

The following codes were added to the policy:
C84.00 C84.01 C84.02 C84.03 C84.04 C84.05 C84.06 C84.07 C84.08 C84.09 C84.10 C84.11 C84.12 C84.13 C84.14 C84.15 C84.16 C84.17 C84.18 C84.19 C84.40 C84.41 C84.42 C84.43 C84.44 C84.45 C84.46 C84.47 C84.48 C84.49 C86.6

Revisions From MA08.068:

01/21/2015

The policy has been reviewed and reissued to communicate the Company’s continuing position on brentuximab vedotin (Adcetris®).

01/01/2015

This is a new policy.

Version Effective Date:

11/18/2024

Version Issued Date:

11/18/2024

Version Reissued Date: