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09-J1000-53

Original Effective Date: 01/01/12

Reviewed: 07/12/17

Revised: 08/15/17

Subject: Brentuximab (Adcetris®) Injection

THIS MEDICAL COVERAGE GUIDELINE IS NOT AN AUTHORIZATION, CERTIFICATION, EXPLANATION OF BENEFITS, OR A GUARANTEE OF PAYMENT, NOR DOES IT SUBSTITUTE FOR OR CONSTITUTE MEDICAL ADVICE. ALL MEDICAL DECISIONS ARE SOLELY THE RESPONSIBILITY OF THE PATIENT AND PHYSICIAN. BENEFITS ARE DETERMINED BY THE GROUP CONTRACT, MEMBER BENEFIT BOOKLET, AND/OR INDIVIDUAL SUBSCRIBER CERTIFICATE IN EFFECT AT THE TIME SERVICES WERE RENDERED. THIS MEDICAL COVERAGE GUIDELINE APPLIES TO ALL LINES OF BUSINESS UNLESS OTHERWISE NOTED IN THE PROGRAM EXCEPTIONS SECTION.

           
Position Statement Dosage/ Administration Billing/Coding Reimbursement Program Exceptions Definitions
           
Related Guidelines Other References Updates  
           

DESCRIPTION:

Brentuximab vedotin (Adcetris®) is an antibody-drug conjugate comprising an anti-CD30 monoclonal antibody and the potent antimicrotubule agent, monomethyl auristatin E (MMAE). The two are attached by a dipeptide link that is stable in plasma but is cleaved by intracellular lysosomal proteases; once inside the CD30-positive tumor cell, MMAE is released and ultimately results in cell cycle arrest and apoptosis. Brentuximab was approved by the US Food and Drug Administration (FDA) in August 2011 for treatment of patients with classical Hodgkin lymphoma (CHL) after failure of autologous hematopoietic stem cell transplantation (auto-HSCT) or after failure of at least two prior multi-agent chemotherapy regimens in patients who are not auto-HSCT candidates, and for systemic anaplastic large-cell lymphoma (ALCL) after failure of at least one prior multi-agent chemotherapy regimen. In August 2015, the FDA approved brentuximab for the treatment of patients with classical Hodgkin lymphoma at high risk of relapse or progression as post-auto-HSCT consolidation.

Hodgkin lymphoma (HL) is a B-cell lymphoma characterized by the presence of scarce, large neoplastic cells (mononucleated Hodgkin cells and multi-nucleated Reed-Sternberg cells) that reside in a complex mixture of non-neoplastic inflammatory cells. The morphology of the cells defines the two major subcategories of Hodgkin lymphoma: classical and nodular lymphocyte-predominant. In classical Hodgkin lymphoma, most of the Reed-Sternberg cells express CD30; however, in nodular lymphocyte-predominant Hodgkin lymphoma, Reed-Sternberg cells rarely express CD30. Systemic ALCL (sALCL) derives from mature T-cells and is considered one of the peripheral T-cell lymphomas. The cells of sALCL uniformly express CD30.

Current National Comprehensive Cancer Network (NCCN) guidelines for the treatment of classical Hodgkin lymphoma, B-cell and T-cell Lymphomas support the use of brentuximab as a single agent in various settings.

POSITION STATEMENT:

Initiation of brentuximab vedotin (Adcetris®) meets the definition of medical necessity when ALL of the following criteria are met:

1. The member’s disease is CD30 positive

2. Brentuximab will be used as monotherapy for the member’s disease

3. The member’s dosage of brentuximab does not exceed 1.8 mg/kg (or 180 mg if >100 kg) every 21 days

4. The member has an indication listed in Table 1 and ALL indication-specific criteria are met:

Table 1: Indications for Use

Disease

Criteria for Use

Adult T-cell Leukemia/Lymphoma

When used for ONE of the following:

1. Member did not attain complete or partial remission with first-line chemotherapy

2. The member has previously completed an autologous hematopoietic stem cell transplantation (auto-HSCT)

Anaplastic Large Cell Lymphoma (ALCL)

When used for ONE of the following:

1. Breast implant-associated ALCL and used as adjuvant therapy for ONE of the following:

a. Localized disease to capsule/implant/breast and ONE of the following:

i. Member had incomplete excision

ii. Member had partial capsulectomy with residual disease

b. Stage II, III or IV disease

2. Cutaneous ALCL and ONE of the following:

a. The member has multifocal lesions

b. The member has regional lymph node involvement

3. Systemic ALCL and used as second-line or subsequent therapy for relapsed or refractory disease

Angioimmunoblastic T-cell lymphoma

When used as second-line or subsequent therapy for relapsed or refractory disease

Classical Hodgkin lymphoma (CHL) - relapsed or refractory

BOTH of the following:

1. The member’s relapsed or refractory CHL is confirmed by biopsy

2. ONE of the following:

a. The member has previously failed an autologous hematopoietic stem cell transplantation (auto-HSCT) for treatment of CHL

b. The member has previously failed two or more prior multi-agent chemotherapy regimens for CHL

c. Brentuximab will be used as second-line therapy prior to auto-HSCT to minimize use of more intensive chemotherapy

d. Member is over 60 years of age and brentuximab will be used as palliative therapy

e. Brentuximab will be used as consolidation or maintenance therapy following auto-HSCT if not previously received

i.

Diffuse Large B-cell Lymphoma

ALL of the following:

1. Member has relapsed or refractory disease

2. Member is not a candidate for high-dose therapy

3. Used as second-line or subsequent therapy

Enteropathy associated T-cell lymphoma

When used as second-line or subsequent therapy for relapsed or refractory disease

Lymphomatoid papulosis (LyP)

BOTH of the following:

1. At least ONE of the following:

a. The member has extensive lesions

b. The member is symptomatic

2. The member has tried and failed at least TWO prior treatments for LyP

Mycosis fungoides (MF)/Sezary syndrome (SS)

When used as first-line chemotherapy for disease classified as ONE of the following:

1. Stage IB-IIA with folliculotropic or large cell transformation

2. Stage IIB with generalized tumor lesions

3. Stage IV non-Sézary or visceral disease

4. Refractory or progressive stage III MF or SS

Peripheral T-cell Lymphoma (not otherwise specified)

When used as second-line or subsequent therapy for relapsed or refractory disease

Approval duration: 6 months (all indications)

NOTE: Quest Diagnostics® can perform the CD30 immunohistochemical assay.

Continuation of brentuximab vedotin (Adcetris®) meets the definition of medical necessity when ALL of the following criteria are met:

1. Authorization/reauthorization for brentuximab has been previously approved by Florida Blue or another health plan in the past 2 years for the treatment of an indication listed in Table 1 OR the member previously met all indication-specific initiation criteria.

2. The member does NOT have progressive disease during treatment with brentuximab per treating physician attestation.

3. Dosage does not exceed 1.8 mg/kg (or 180 mg if >100 kg) every 21 days.

Approval duration: 1 year

DOSAGE/ADMINISTRATION:

THIS INFORMATION IS PROVIDED FOR INFORMATIONAL PURPOSES ONLY AND SHOULD NOT BE USED AS A SOURCE FOR MAKING PRESCRIBING OR OTHER MEDICAL DETERMINATIONS. PROVIDERS SHOULD REFER TO THE MANUFACTURER’S FULL PRESCRIBING INFORMATION FOR DOSAGE GUIDELINES AND OTHER INFORMATION RELATED TO THIS MEDICATION BEFORE MAKING ANY CLINICAL DECISIONS REGARDING ITS USAGE.

FDA-approved: brentuximab is indicated for treatment of classical Hodgkin lymphoma (HL) after failure of autologous hematopoietic stem cell transplantation (auto-HSCT) or after failure of at least 2 prior multi-agent chemotherapy regimens in persons who are not auto-HSCT candidates. It is also indicated for treatment of systemic anaplastic large cell lymphoma (sALCL) after failure of at least one prior multi-agent chemotherapy regimen, and treatment of classical HL at high risk of relapse or progression as post-auto-HSCT consolidation. The recommended dose is 1.8 mg/kg administered intravenously (IV) over 30 minutes every 3 weeks. The dose for persons weighing greater than 100 kg should be calculated based on a weight of 100 kg (max dose of 180 mg every 3 weeks). Therapy should be continued until disease progression or unacceptable toxicity. For classical HL post-auto-HSCT consolidation treatment, initiate treatment within 4 to 6 weeks post-auto-HSCT or upon recovery from auto-HSCT. Treatment should continue until a maximum of 16 cycles, disease progression, or unacceptable toxicity.

Dose Adjustments

• Peripheral Neuropathy: manage using a combination of dose delay and reduction to 1.2 mg/kg. For new or worsening Grade 2 or 3 neuropathy, dosing should be held until neuropathy improves to Grade 1 or baseline and then restarted at 1.2 mg/kg. For Grade 4 peripheral neuropathy, brentuximab should be discontinued.

• Neutropenia: manage using a combination of dose delay and reduction. The dose of brentuximab should be held for Grade 3 or 4 neutropenia until resolution to baseline or Grade 2 or lower. Growth factor support should be considered for subsequent cycles in persons who experience Grade 3 or 4 neutropenia. In persons with recurrent Grade 4 neutropenia despite growth factor support, discontinuation or dose reduction to 1.2 mg/kg may be considered.

• Renal impairment: No adjustment is needed in patients with mild to moderate impairment (CrCl ≥30 mL/min). Use should be avoided in patients with severe impairment (CrCl <30 mL/min).

• Hepatic impairment: For mild impairment (Child-Pugh A) the dosage should be reduced to 1.2 mg/kg (up to 120 mg) over 30 min every 3 weeks. Use should be avoided in patients with moderate (Child-Pugh B) or severe (Child-Pugh C) impairment.

Drug Availability: brentuximab is available as a 50 mg single-use vial for reconstitution.

PRECAUTIONS:

Boxed Warning:

JC virus infection resulting in progressive multifocal leukoencephalopathy (PML) and death can occur in persons receiving brentuximab.

CONTRAINDICATIONS:

Concomitant use with bleomycin is contraindicated due to pulmonary toxicity.

WARNINGS/PRECAUTIONS

• Peripheral neuropathy: Treating physicians should monitor members for neuropathy and institute dose modifications accordingly.

• Anaphylaxis and infusion reactions: If an infusion reaction occurs, the infusion should be interrupted and appropriate medical management instituted. If anaphylaxis occurs, the infusion should be discontinued immediately and appropriate medical management instituted.

• Hematologic Toxicities: Prolonged (≥1 week) severe neutropenia and Grade 3 or Grade 4 thrombocytopenia or anemia can occur. Monitor complete blood counts prior to each dose of brentuximab. If Grade 3 or 4 neutropenia develops, manage by dose delays, reductions or discontinuation.

• Serious infections and opportunistic infections: Closely monitor patients for the emergence of bacterial, fungal or viral infections.

Tumor Lysis Syndrome: persons with rapidly proliferating tumor and high tumor burden are at risk of tumor lysis syndrome and these individuals should be monitored closely and appropriate measures taken.

• Hepatotoxicity: Serious cases of hepatotoxicity, including fatal outcomes, have occurred. Monitor liver enzymes and bilirubin. Patients experiencing new, worsening, or recurrent hepatotoxicity may require a delay, change in dose, or discontinuation.

• Pulmonary Toxicity: Evaluate new or worsening pulmonary symptoms.

• Progressive Multifocal Leukoencephalopathy (PML): Monitor neurologic function; hold brentuximab if PML is suspected and discontinue brentuximab if PML is confirmed.

• Serious Dermatologic Reactions: Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN), including fatal outcomes, have been reported. If SJS or TEN occurs, discontinue brentuximab and administer appropriate medical therapy.

• Gastrointestinal complications: Monitor patients for new or worsening symptoms.

• Use in pregnancy: Fetal harm can occur. Pregnant women should be advised of the potential hazard to the fetus.

BILLING/CODING INFORMATION:

HCPCS Coding

J9042

Injection, brentuximab vedotin, 1 mg

ICD-10 Diagnoses Codes That Support Medical Necessity

C81.10 – C81.79

Hodgkin lymphoma

C81.90 – C81.99

Hodgkin lymphoma, unspecified

C82.20 – C82.49

Follicular lymphoma grade III

C83.30 – C83.39

Diffuse large B-cell lymphoma

C84.00 – C84.09

Mycosis fungoides

C84.10 – C84.19

Sézary disease

C84.40 – C84.49

Peripheral T-cell lymphoma, not classified

C84.60 – C84.79

Anaplastic large 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

C91.50 – C91.52

Adult T-cell lymphoma/leukemia

REIMBURSEMENT INFORMATION:

Refer to section entitled POSITION STATEMENT.

PROGRAM EXCEPTIONS:

Federal Employee Program (FEP): Follow FEP guidelines.

State Account Organization (SAO): Follow SAO guidelines.

Medicare Advantage Products: No National Coverage Determination (NCD) and/or Local Coverage Determination (LCD) were found at the time of the last guideline revised date.

DEFINITIONS:

B Symptoms: The presence of one or more of the following systemic symptoms within 6 months prior to diagnosis are an unfavorable risk factor: (1) unexplained fevers >38 degrees C, (2) drenching night sweats, or (3) weight loss >10% of body weight.

Hodgkin lymphoma (HL): an uncommon malignancy involving lymph nodes and the lymphatic system. The World Health Organization (WHO) classification divides HL into two main types: classical Hodgkin lymphoma (CHL) and nodular lymphocyte-predominant Hodgkin lymphoma (NLPHL). In the U.S., CHL account for 95% of all HL cases. Classical HL is divided into four subtypes: nodular sclerosis CHL, mixed cellularity, lymphocyte-depleted CHL, and lymphocyte-rich CHL.

Primary treatment of CHL: Clinical management involves initial treatment with chemotherapy or combined modality therapy (i.e., chemotherapy + radiation), followed by restaging at the completion of chemotherapy to assess treatment response. The specific therapy and follow-up recommendations are based on the staging of the CHL; however, all recommendations have an initial multi-agent chemotherapy component.

Progressive multifocal leukoencephalopathy (PML): also known as progressive multifocal leukoencephalitis, is a rare and usually fatal viral disease that is characterized by progressive damage or inflammation of the white matter of the brain at multiple locations. It occurs almost exclusively in people with severe immune deficiency, such as transplant patients on immunosuppressive medications, patients receiving certain kinds of chemotherapy, AIDS patients and patients treated with other agents that suppress the immune system. It is caused by a virus, the JC virus, which is normally present and kept under control by the immune system. Immunosuppressive drugs prevent the immune system from controlling the virus.

Staging of HL: After initial diagnosis, patients are divided into either stage I-II (early stage) or stage III-IV (advanced-stage) disease based on the Ann Arbor staging system. Patients with stage I-II are further classified based on presence or absence of unfavorable risk factors into stage IA-IIA (favorable), stage I-II (unfavorable with bulky disease), and stage I-II (unfavorable with non-bulky disease). The unfavorable risk factors for stage I-II disease include bulky mediastinal disease or bulky disease greater than 10 cm, B symptoms, erythrocyte sedimentation rate (ESR) >50, and >3 nodal site of disease. For stage III-IV disease, an International Prognostic Score (IPS) is determined based on the number of adverse prognostic factors present at diagnosis. These 7 factors include: age >45 years, male gender, stage IV disease, albumin <4 g/dL, hemoglobin <10.5 g/dL, WBC <15,000/m3, and lymphocyte count <600/mm3 or <8% of WBC.

Stevens–Johnson syndrome (SJS): a form of a life-threatening skin condition, in which cell death causes the epidermis to separate from the dermis. The syndrome is thought to be a hypersensitivity complex that affects the skin and the mucous membranes. Although the majority of cases are idiopathic (without a known cause), the main class of known causes is medication, followed by infections and, rarely, cancers.

Tumor Lysis syndrome (TLS): a group of metabolic complications that can occur after treatment of cancer, usually lymphomas and leukemias, and sometimes even without treatment. These complications are caused by the break-down products of dying cancer cells and include hyperkalemia, hyperphosphatemia, hyperuricemia and hyperuricosuria, hypocalcemia, and consequent acute uric acid nephropathy and acute renal failure

RELATED GUIDELINES:

Autologous Bone Marrow and Stem Cell Transplantation, 02-38241-01
Bortezomib (Velcade®) IV, 09-J0000-92

Carboplatin (Paraplatin®) IV, 09-J0000-93

Doxorubicin HCl Liposome (Doxil®) IV, 09-J0000-91

Gemcitabine (Gemzar®), 09-J0000-96

Granulocyte Colony Stimulating Factors, 09-J0000-62

Intensity-Modulated Radiation Therapy (IMRT), 04-77260-22

Lenalidomide (Revlimid®), 09-J0000-80

Oxaliplatin (Eloxatin®) IV, 09-J1000-00

Pralatrexate (Folotyn®) IV, 09-J1000-18

Rituximab (Rituxan®), 09-J0000-59

Vinorelbine Tartrate (Navelbine®) IV, 09-J1000-03

OTHER:

None.

REFERENCES:

  1. Adcetris (brentuximab vedotin) [package insert]. Seattle Genetics, Inc. Bothell (WA): September 2016.
  2. Brentuximab. In McEvoy GK, editor. AHFS drug information 2017 [monograph on the internet]. Bethesda (MD): American Society of Health-System Pharmacists; 2017 [cited 2017 June 20].
  3. Clinical Pharmacology [database online]. Tampa, FL: Gold Standard, Inc.;2017. URL www.clinicalpharmacilogy-ip.com. Accessed 6/20/17.
  4. Fanale MA, Horwitz SM, Forero-Torres A, et al. Brentuximab vedotin in the front-line treatment of patients with CD30+ peripheral T-cell lymphomas: results of a phase I study. J Clin Oncol. 2014 Oct 1;32(28):3137-43. doi: 10.1200/JCO.2013.54.2456. Epub 2014 Aug 18.
  5. Horwitz SM, Advani RH, Bartlett NL, et al. Objective responses in relapsed T-cell lymphomas with single-agent brentuximab vedotin. Blood. 2014 May 15;123(20):3095-100. doi: 10.1182/blood-2013-12-542142. Epub 2014 Mar 20.
  6. Jacobsen ED, Sharman JP, Oki Y, et al. Brentuximab vedotin demonstrates objective responses in a phase 2 study of relapsed/refractory DLBCL with variable CD30 expression. Blood. 2015 Feb 26;125(9):1394-402. doi: 10.1182/blood-2014-09-598763. Epub 2015 Jan 8.
  7. Mehra T, Ikenberg K, Moos RM, et al. Brentuximab as a treatment for CD30+ mycosis fungoides and Sézary syndrome. JAMA Dermatol. 2015 Jan;151(1):73-7. doi: 10.1001/jamadermatol.2014.1629.
  8. Micromedex® Healthcare Series [Internet Database]. Greenwood Village, Colo: Thomson Healthcare. Updated periodically. Accessed 6/20/17.
  9. Moskowitz CH, Nademanee A, Masszi T, et al. Brentuximab vedotin as consolidation therapy after autologous stem-cell transplantation in patients with Hodgkin's lymphoma at risk of relapse or progression (AETHERA): a randomised, double-blind, placebo-controlled, phase 3 trial. Lancet. 2015 May 9;385(9980):1853-62.
  10. National Comprehensive Cancer Network. Cancer Guidelines. Cancer Guidelines and Drugs and Biologics Compendium. Accessed 6/22/17.
  11. National Comprehensive Cancer Network. Clinical Practice Guidelines in Oncology. Version 3.2017. B-cell Lymphomas. Available at http://www.nccn.org/professionals/physician_gls/PDF/b-cell.pdf. Accessed 6/26/17.
  12. National Comprehensive Cancer Network. Clinical Practice Guidelines in Oncology. Version 1.2017. Hodgkin Lymphomas. Available at http://www.nccn.org/professionals/physician_gls/PDF/b-cell.pdf. Accessed 6/26/17.National Comprehensive Cancer Network. Clinical Practice Guidelines in Oncology. Version 2.2017. T-cell Lymphomas. Available at http://www.nccn.org/professionals/physician_gls/PDF/t-cell.pdf. Accessed 6/26/17.

COMMITTEE APPROVAL:

This Medical Coverage Guideline (MCG) was approved by the BCBSF Pharmacy Policy Committee on 07/12/17.

GUIDELINE UPDATE INFORMATION:

11/15/11

New Medical Coverage Guideline.

08/15/12

Review and revision to guideline; consisting of updating precautions, coding and references.

01/01/13

Annual HCPCS Update: added HCPCS code J9042.

08/15/13

Review and revision to guideline; consisting of revising position statement to require CD30 positivity and brentuximab use as monotherapy; revised description section; revised and reformatted dosage/administration and precautions section; updated coding, program exceptions and references.

04/15/14

Revision to guideline; consisting of removing 16-cycle limit.

08/15/14

Review and revision to guideline; consisting of updating references.

08/15/15

Review and revision to guideline; consisting of description, position statement, dosage/administration, precautions, billing/coding information, and references.

10/15/15

Revision to guideline consisting of updating description and dosage/administration sections, references, and definitions, and reformatting the position statement.

11/01/15

Revision: ICD-9 Codes deleted.

08/15/16

Review and revision to guideline; consisting of updating position statement, coding and references.

10/01/16

Update to ICD-10 codes.

08/15/17

Review and revision to guideline; consisting of updating position statement, coding, and references.

Date Printed: August 22, 2017: 06:53 AM