• Grade 4 peripheral neuropathy
• Anaphylactic reactions
• Stevens-Johnson syndrome

The requirements of the Horizon BCBSNJ Brentuximab Vedotin (Adcetris) Program may require a precertification/prior authorization via MagellanRx Management. These requirements are member-specific: please verify member eligibility and requirements through the Horizon Provider Portal (www.horizonblue.com/provider). Ordering clinicians should request pre-certification from MagellanRx Management at ih.magellanrx.com or call 1-800-424-4508 (when applicable).

1. Brentuximab vedotin (Adcetris) is medically necessary for ANY of the following FDA approved indications:

• Hodgkin’s lymphoma when ALL of the following criteria are met:
  • Member is ≥18 years of age AND
  • After failure of autologous stem cell transplant (ASCT) OR
  • After failure of a minimum of two prior multi-agent chemotherapy regimens in patients who are not autologous hematopoietic stem cell transplantation (auto-HSCT) candidates OR
  • At high risk of relapse or progression as post-auto-HSCT consolidation (high risk defined as one of the following according to status after initial therapy: refractory classical HL, relapsed disease occurring within 12 months, or relapsed disease with extra-nodal involvement) OR
  • Previously untreated Stage III or IV Hodgkin’s lymphoma in combination with doxorubicin, vinblastine, and dacarbazine
• Systemic anaplastic large cell lymphoma (sALCL) when ALL of the following criteria are met:
  • Member is ≥18 years of age
  • Failure of at least one prior multi-agent chemotherapy regimen
  • Disease has confirmed CD30 positivity
• Primary cutaneous anaplastic large cell lymphoma (pcALCL) or CD30-expressing mycosis fungoides (MF) when ALL of the following criteria are met:
  • Member is ≥18 years of age
  • Patients with pcALCL who have received prior radiation therapy or at least one prior systemic therapy OR patients with MF who have received at least one prior systemic therapy
  • Disease has confirmed CD30 positivity
  • ECOG status of <2
• Previously untreated systemic anaplastic large cell lymphoma (sALCL) or other CD30-expressing peripheral T-cell lymphomas (PTCL), including angioimmunobalstic T-cell lymphoma and PTCL not otherwise specified, in combination with cyclophosphamide, doxorubicin, and prednisone when ALL of the following criteria are met:
  • Member is ≥18 years of age
  • Members with newly diagnosed, CD30-positive mature T-cell lymphomas
  • ECOG status of less than or equal to 2

[INFORMATIONAL NOTE: According to the FDA approved package insert, brentuximab vedotin (Adcetris) carries a Black Box Warning for the risk of JC virus infection resulting in progressive multifocal leukoencephalopathy (PML). Possible contributory factors include prior therapies and underlying disease that may cause immunosuppression. Diagnosis of PML should be considered in any patient presenting with new-onset signs and symptoms of central nervous system abnormalities. Evaluation of PML includes, but is not limited to, consultation with a neurologist, brain MRI, and lumbar puncture or brain biopsy. Hold brentuximab dosing for any suspected case of PML and discontinue therapy is diagnosis of PML is confirmed.

As per the FDA approved package insert, concomitant use of Brentuximab vedotin (Adcetris) with bleomycin is contraindicated due to the risk of pulmonary toxicity].

A. Classical HL post-auto-HSCT consolidation treatment
• Approved for a 48 week period at the recommended dose of 1.8 mg/kg up to 180 mg every 3 weeks until a maximum of 16 doses, disease progression, or unacceptable toxicity
• Initiate Adcetris treatment within 4–6 weeks post-auto-HSCT or upon recovery from auto-HSCT
• The dose for patients weighing greater than 100 kg should be calculated based on a weight of 100 kg.
B. Primary cutaneous anaplastic large cell lymphoma (pcALCL) or CD30-expressing mycosis fungoides (MF) who have received prior systemic therapy
• approved for a 48 week period at the recommended dose of 1.8 mg/kg up to 180 mg every 3 weeks until a maximum of 16 doses, disease progression, or unacceptable toxicity.
• The dose for patients weighing greater than 100 kg should be calculated based on a weight of 100 kg.
C. Previously untreated Stage III or IV Classical Hodgkin Lymphoma
· Approved for a 24 week period at the recommended dose of 1.2 mg/kg up to a maximum of 120 mg given every 2 weeks until a maximum of 12 doses, disease progression, or unacceptable toxicity.
· The dose for patients weighing greater than 100 kg should be calculated based on a weight of 100 kg.
D. Previously untreated systemic anaplastic large cell lymphoma or other CD30-expressing peripheral T-cell lymphoma, including angioimmunoblastic T-cell lymphoma and PTCL not otherwise specified, in combination with cyclophosphamide, doxorubicin, and prednisone
· Approved at the dose of 1.8mg/kg up to a maximum of 180mg every 3 weeks with each cycle of chemotherapy for 6 to 8 doses
· The dose for patients weighing greater than 100 kg should be calculated based on a weight of 100 kg.
E. Hodgkin’s lymphoma after failure of ASCT or failure of two prior multi-agent chemotherapy regimens OR relapsed systemic anaplastic large cell lymphoma (sALCL)
• Approved for 6 months at the dose of 1.8mg/kg up to a maximum of 180mg every 3 weeks until disease progression or unacceptable toxicity
• The dose for patients weighing greater than 100 kg should be calculated based on a weight of 100 kg.
Recommended dose modification based on the FDA approved package insert:

Dose	Degree of impairment	Recommended dose
Renal Impairment
1.2 mg/kg up to a maximum of 120 mg* every 2 weeks	Normal Mild (CrCL greater than 50-80 mL/min) Moderate (CrCL 30-50 mL/min)	1.2 mg/kg up to a maximum of 120 mg* every 2 weeks
	Severe (CrCL less than 30 mL/min)	Avoid use
1.8 mg/kg up to a maximum of 180 mg* every 3 weeks	Normal Mild (CrCL greater than 50-80 mL/min) Moderate (CrCL 30-50 mL/min)	1.8 mg/kg up to a maximum of 180 mg* every 3 weeks
	Severe (CrCL less than 30 mL/min)	Avoid use
Hepatic Impairment
1.2 mg/kg up to a maximum of 120 mg* every 2 weeks	Normal	1.2 mg/kg up to a maximum of 120 mg* every 2 weeks
	Mild (Child-Pugh A)	0.9 mg/kg up to a maximum of 90 mg* every 2 weeks
	Moderate (Child-Pugh B) Severe (Child-Pugh C)	Avoid use
1.8 mg/kg up to a maximum of 180 mg* every 3 weeks	Normal	1.8 mg/kg up to a maximum of 180 mg* every 3 weeks
	Mild (Child-Pugh A)	1.2 mg/kg up to a maximum of 120 mg* every 3 weeks
	Moderate (Child-Pugh B) Severe (Child-Pugh C)	Avoid use
Peripheral Neuropathy
1.2 mg/kg up to a maximum of 120 mg* every 2 weeks	Grade 2	Reduce dose to 0.9 mg/kg up to a maximum of 90 mg* every 2 weeks
	Grade 3	Hold ADCETRIS dosing until improvement to Grade 2 or lower Restart at 0.9 mg/kg up to a maximum of 90 mg* every 2 weeks Consider modifying the dose of other neurotoxic chemotherapy agents
	Grade 4	Discontinue dosing
1.8 mg/kg up to a maximum of 180 mg* every 3 weeks	Grade 2	Reduce dose to 0.9 mg/kg up to a maximum of 90 mg* every 2 weeks
	Grade 3	Hold ADCETRIS dosing until improvement to Grade 2 or lower Restart at 0.9 mg/kg up to a maximum of 90 mg* every 2 weeks Consider modifying the dose of other neurotoxic chemotherapy agents
	Grade 4	Discontinue dosing
Neutropenia
1.2 mg/kg up to a maximum of 120 mg* every 2 weeks	Grade 3 or 4	Administer G-CSF prophylaxis for subsequent cycles for patients not receiving primary G-CSF prophylaxis
1.8 mg/kg up to a maximum of 180 mg* every 3 weeks	Grade 3 or 4	Hold dosing until improvement to baseline or Grade 2 or lower Consider G-CSF prophylaxis for subsequent cycles
	Recurrent Grade 4 despite G-CSF prophylaxis	Consider discontinuation or dose reduction to 1.2 mg/kg up to a maximum of 120 mg* every 3 weeks

a. Member has a diagnosis of relapsed Hodgkin's lymphoma OR relapsed systemic anaplastic large cell lymphoma (sALCL)
b. Member has not experienced unacceptable toxicity while receiving treatment with brentuximab vedotin (e.g. progressive multifocal leukoencephalopathy, peripheral neuropathy, anaphylaxis and infusion reactions, hematologic toxicities (thrombocytopenia, neutropenia and anemia), serious infections, tumor lysis syndrome, increased toxicity in patients with severe renal (CrCl < 30 ml/min) and hepatic impairment (Child-Pugh B or C), hepatotoxicity, pulmonary toxicity, serious dermatologic reactions, gastrointestinal complications, etc.)
c. Member has disease response with treatment defined by stabilization of disease or decrease in size of tumor or tumor spread

• Hodgkin Lymphoma- Classical Hodgkin lymphoma
  • Second-line or subsequent systemic therapy (if not previously used) for relapsed or refractory disease in patients≥ 18 years of age as a single agent in combination with bendamustine
  • Maintenance therapy following high-dose therapy and autologous stem cell rescue (HDT/ASCR) for relapsed or refractory disease for patients with high risk* of relapse if Deauville 1-3 prior to transplant or if Deauville 4 prior to transplant (*high risk defined by having 2 or more of the following risk factors: remission duration less than 1 year, extranodal involvement, PET+ response at time of transplant, B symptoms, and/or >1 salvage/subsequent therapy regimen)
  • Palliative therapy as a single agent for relapsed or refractory classic Hodgkin Lymphoma in older adults (age >60 years)
  • Primary treatment in combination with AVD (doxorubicin, vinblastine, dacarbazine) for stage III-IV disease in patients ≥ 18 years of age if there is no know neuropathy and patient has either an international prognostic score(IPS) ≥4 or bleomycin is contraindicated
• T Cell Lymphomas- Peripheral T-cell lymphoma
  • Preferred first-line therapy for stage III, IV ALK-positive anaplastic large cell lymphoma as a component of brentuximab vedotin + CHP (cyclophosphamide, doxorubicin, prednisone)
  • Preferred first-line therapy for CD30+ stage I-IV peripheral T-cell lymphoma not otherwise specified, ALK-negative anaplastic large cell lymphoma, angioimmunoblastic T-cell lymphoma, enteropathy-associated T-cell lymphoma, monomorphic epitheliotropic intestinal T-cell lymphoma, nodal peripheral T-cell lymphoma with TFH phenotype, or follicular T-cell lymphoma, as a component of brentuximab vedotin + CHP (cyclophosphamide, doxorubicin, prednisone)
  • Preferred second-line and subsequent therapy for relapsed/refractory anaplastic large cell lymphoma, CD30+ peripheral T-cell lymphoma, or CD30+ angioimmunoblastic T-cell lymphoma, as a single agent
  • Preferred first-line therapy for stage I, II ALK-positive anaplastic large cell lymphoma as a component of brentuximab vedotin + CHP (cyclophosphamide, doxorubicin, prednisone) for 6 cycles +/- ISRT
• T- Cell Lymphomas – breast implant-associated ALCL :Adjuvant systemic therapy for localized disease to capsule/implant/breast following incomplete excision or partial capsulectomy with residual disease, if node positive or radiation therapy is not feasible, or consider for extended disease (stage II - IV) as a single agent or as a component of brentuximab vedotin + CHP (cyclophosphamide, doxorubicin, prednisone)
• T- Cell Lymphomas – Adult T-cell Leukemia/lymphoma: Preferred second-line or subsequent therapy as a single agent for nonresponders to first-line therapy for acute or lymphoma subtypes (for CD30 expressing cases) OR
  • Used as a component of brentuximab vedotin + CHP (cyclophosphamide, doxorubicin, prednisone) for CD30+ cases as
    • chemotherapy in nonresponders to first-line therapy for chronic/smoldering subtype
    • first-line therapy for acute subtype
    • 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 - Extranodal NK/T-Cell Lymphoma, nasal type: Preferred therapy as a single agent for CD30+ relapsed/refractory disease following additional therapy with an alternate combination chemotherapy regimen (asparaginase-based) not previously used
• T-Cell Lymphomas - Hepatosplenic Gamma-Delta T-Cell Lymphoma: Preferred second-line and subsequent therapy as a single agent for CD30+ refractory disease after 2 primary treatment regimens OR Used a component of brentuximab vedotin + CHP (cyclophosphamide, doxorubicin, prednisone) for CD30+ cases as preferred primary treatment or consider as an alternate induction regimen if not used in primary treatment
• Primary Cutaneous Lymphomas – Primary Cutaneous CD30+ T-Cell Lymphoproliferative Disorder
  • Therapy for primary cutaneous anaplastic large cell lymphoma (ALCL) with multifocal lesions, or cutaneous ALCL with regional nodes (excludes systemic ALCL), as a single agent for relapsed/refractory disease or primary treatment (preferred) OR
  • 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
  • Therapy for cutaneous anaplastic large cell lymphoma (ALCL) with regional nodes (excludes systemic ALCL) as a component of brentuximab vedotin + CHP (cyclophosphamide, doxorubicin, prednisone) for primary treatment or relapsed/refractory disease
· · B-Cell Lymphomas -
• Follicular Lymphoma: Treatment of histologic transformation to CD30+ diffuse large B-cell lymphoma in patients who have received multiple lines of chemoimmunotherapy for indolent or transformed disease
• Histologic transformation of Marginal zone Lymphoma to Diffuse large B-cell lymphoma: Treatment of patients who have received multiple lines of chemoimmunotherapy for indolent or transformed disease
• Diffuse large B-cell lymphoma:
  • Second-line or subsequent therapy for partial response, no response, relapsed, progressive, or refractory CD30+ disease in noncandidates for transplant
  • Second-line or subsequent therapy for partial response, no response, relapsed, progressive, or refractory CD30+ primary cutaneous diffuse large B-cell lymphoma, leg type in noncandidates for transplant
• High grade B cell lymphoma: Second-line or subsequent therapy for partial response, no response, relapsed, progressive, or refractory CD30+ disease in noncandidates for transplant
• AIDS-related B cell lymphoma: Second-line or subsequent therapy for relapse of CD30+ AIDS-related diffuse large B-cell lymphoma, primary effusion lymphoma, and HHV8-positive diffuse large B-cell lymphoma, not otherwise specified (NOS) in noncandidates for transplant
• Post-transplant lymphoproliferative disorders: Second-line and subsequent therapy for patients with partial response, persistent or progressive disease after receiving chemoimmunotherapy as first-line treatment for CD30+ monomorphic PTLD (B-cell type)
· Primary Cutaneous Lymphomas - Mycosis Fungoides/Sezary Syndrome: Preferred systemic therapy as primary treatment for
• stage IB-IIA MF with a higher disease burden (eg, predominantly plaque disease), with or without skin-directed therapy
• stage IIB MF with limited tumor lesions, with or without local radiation therapy
• stage IIB MF with generalized tumor lesions, with or without skin-directed therapy
• stage III MF, with or without skin-directed therapy
• stage IV Sezary syndrome
• Primary Cutaneous Lymphomas - Mycosis Fungoides/Sezary Syndrome :Systemic therapy primary treatment for
  • stage IB-IIA MF with a higher disease burden (eg, predominantly plaque disease) and B1 blood involvement, with or without skin-directed therapy
  • stage IIB MF with generalized tumor lesions, with or without skin-directed therapy (preferred)
  • stage III MF, with or without skin-directed therapy
  • stage IV Sezary syndrome, with or without skin-directed therapy
  • stage IV non-Sezary or visceral disease (solid organ), with or without radiation therapy for local control (preferred)
  • large cell transformation (LCT) with generalized cutaneous or extracutaneous lesions, with or without skin-directed therapy (preferred)
• Primary Cutaneous Lymphomas - Mycosis Fungoides/Sezary Syndrome :Systemic therapy for
  • relapsed or persistent stage IB-IIA MF with a higher disease burden (eg, predominantly plaque disease), with or without skin-directed therapy
  • relapsed or persistent stage IIB MF with limited tumor lesions, with or without local radiation therapy
  • stage IIB MF with limited tumor lesions refractory to multiple previous therapies, with or without skin-directed therapy
  • relapsed or persistent stage IIB MF with generalized tumor lesions, with or without skin-directed therapy
  • stage IIB MF with generalized tumor lesions refractory to multiple previous therapies
  • relapsed or persistent stage III MF, with or without skin-directed therapy
  • stage III MF that is refractory to multiple previous therapies
  • relapsed or persistent stage IV Sezary syndrome
  • relapsed or persistent stage IV non Sezary or visceral disease (solid organ), with or without radiation therapy for local control
  • large cell transformation (LCT) with limited cutaneous lesions that is refractory to multiple previous therapies
  • relapsed or persistent LCT with generalized cutaneous or extracutaneous lesions, with or without skin-directed therapy

[INFORMATIONAL NOTE: Administration of over 16 doses of Brentuximab vedotin (Adcetris) or beyond 48 weeks of therapy of Brentuximab vedotin (Adcetris)) have not been studied in clinical trials for all indications except relapsed Hodgkin's lymphoma OR relapsed systemic anaplastic large cell lymphoma (sALCL), and the FDA approved labeling is only for a period of 16 doses or 48 weeks for all indications except relapsed Hodgkin's lymphoma OR relapsed systemic anaplastic large cell lymphoma (sALCL).]

There is no National Coverage Determination (NCD). In the absence of an NCD, coverage decisions are left to the discretion of Local Medicare Carriers. Novitas Solutions, Inc, the Local Medicare Carrier for jurisdiction JL, has not issued a determination for this service. Therefore, Medicare Advantage Products will follow the Horizon Policy.

Medicaid Coverage

For Horizon NJ Health members, please follow this link for the corresponding HNJH drug policy https://services3.horizon-bcbsnj.com/ddn/NJhealthWeb.nsf

________________________________________________________________________________________

Horizon BCBSNJ Medical Policy Development Process:

This Horizon BCBSNJ Medical Policy (the “Medical Policy”) has been developed by Horizon BCBSNJ’s Medical Policy Committee (the “Committee”) consistent with generally accepted standards of medical practice, and reflects Horizon BCBSNJ’s view of the subject health care services, supplies or procedures, and in what circumstances they are deemed to be medically necessary or experimental/ investigational in nature. This Medical Policy also considers whether and to what degree the subject health care services, supplies or procedures are clinically appropriate, in terms of type, frequency, extent, site and duration and if they are considered effective for the illnesses, injuries or diseases discussed. Where relevant, this Medical Policy considers whether the subject health care services, supplies or procedures are being requested primarily for the convenience of the covered person or the health care provider. It may also consider whether the services, supplies or procedures are more costly than an alternative service or sequence of services, supplies or procedures that are at least as likely to produce equivalent therapeutic or diagnostic results as to the diagnosis or treatment of the relevant illness, injury or disease. In reaching its conclusion regarding what it considers to be the generally accepted standards of medical practice, the Committee reviews and considers the following: all credible scientific evidence published in peer-reviewed medical literature generally recognized by the relevant medical community, physician and health care provider specialty society recommendations, the views of physicians and health care providers practicing in relevant clinical areas (including, but not limited to, the prevailing opinion within the appropriate specialty) and any other relevant factor as determined by applicable State and Federal laws and regulations.

___________________________________________________________________________________________________________________________

Index:
Brentuximab Vedotin (Adcetris)
Adcetris (Brentuximab Vedotin)

References:
1. Adcetris^® [package insert]. Seattle Genetics, Inc. Bothell, WA October 2019.

2. Adcetris^TM. Clinicaltrial.gov. Accessed on 11/26/2019. Available at: http://clinicaltrial.gov/ct2/results?term=brentuximab

3. Chen RW, Gopal AK, Smith SE, et al. Results from a pivotal phase II study of brentuximab vedotin (SGN-35) in patients with relapsed or refractory Hodgkin lymphoma (HL). ASCO Meeting Abstracts 2011;29(15_suppl):8031.

4. Pro B, Advani R, Brice P, et al. Durable remissions with brentuximab vedotin (SGN-35): Updated results of a phase II study in patients with relapsed or refractory systemic anaplastic large cell lymphoma (sALCL). ASCO Meeting Abstracts 2011;29(15_suppl):8032.

5. NCCN Guidelines Version 2.2014 Hodgkin Lymphoma. National Comprehensive Cancer Network, Inc. 2.2012. Available at: http://www.nccn.org/professionals/physician_gls/pdf/hodgkins.pdf [Accessed 11/22/2019].

6. National Comprehensive Cancer Network – Drugs & Biologics Compendium. Brentuximab vedotin. Available at: http://www.nccn.org/professionals/drug_compendium/MatrixGenerator/PrintMatrix.aspx?AID=374. [Accessed: 11/2019].

7. ClinicalTrials.gov. Study of SGN-30 (Anti-CD30 mAb) in Patients With Primary Cutaneous Anaplastic Large Cell Lymphoma. Available at: https://clinicaltrials.gov/ct2/show/NCT00099255. Accessed November 2019.

8. Connors JM, Jurczak W, Straus DJ, et al. Brentuximab Vedotin with Chemotherapy for Stage III or IV Hodgkin's Lymphoma. N Engl J Med. 2018;378(4):331-344.

9. Adcetris^TM. Clinicaltrial.gov. Accessed on 11/22/2019. Available at: https://clinicaltrials.gov/ct2/show/NCT01777152

10. ClinicalTrials.gov. Brentuximab Vendotin. [Available from: https://clinicaltrials.gov/ct2/results?cond=&term=adcetris&cntry=&state=&city=&dist= [Accessed 11/22/2019]

11. ClinicalTrials.gov. A Phase 3 Trial of Brentuximab Vedotin(SGN-35) Versus Physician's Choice (Methotrexate or Bexarotene) in Participants With CD30-Positive Cutaneous T-Cell Lymphoma (ALCANZA Study) (ALCANZA). Accessed on 11/22/2019. Available at: https://clinicaltrials.gov/ct2/show/NCT01578499

12. ClinicalTrials.gov. A Phase 2 Open Label Trial of Brentuximab Vedotin (SGN-35) for Systemic Anaplastic Large Cell Lymphoma. NCT00866047. Available at: https://clinicaltrials.gov/ct2/show/NCT00866047 .

13. ClinicalTrials.gov. A Pivotal Open-Label Trial of Brentuximab Vedotin for Hodgkin Lymphoma, NCT00848926. Available at: https://clinicaltrials.gov/ct2/show/NCT00848926

Codes:
(The list of codes is not intended to be all-inclusive and is included below for informational purposes only. Inclusion or exclusion of a procedure, diagnosis, drug or device code(s) does not constitute or imply authorization, certification, approval, offer of coverage or guarantee of payment.)

CPT*

J9042