Last Review Date: 12/01/2020

Date of Origin: 02/28/2012

Dates Reviewed: 06/2012, 09/2012, 09/2012, 12/2012, 03/2013, 06/2013, 09/2013, 12/2013, 03/2014, 06/2014, 09/2014, 12/2014, 03/2015, 05/2015, 08/2015, 11/2015, 02/2016, 05/2016, 08/2016, 11/2016, 02/2017, 05/2017, 08/2017, 11/2017, 02/2018, 04/2018, 09/2018, 12/2018, 03/2019, 06/2019, 09/2019, 12/2019, 03/2020, 06/2020, 09/2020, 12/2020

I. Length of Authorization 

Coverage will be provided for six months and may be renewed.

• Treatment for Adult cHL post-auto HSCT, Pediatric cHL, Mycosis Fungoides (MF)/Sezary Syndrome (SS), and Primary Cutaneous CD30+ T-Cell Lymphoproliferative Disorders has a maximum of 16 cycles.
• Treatment of previously untreated Adult Stage III or IV Classical Hodgkin Lymphoma (cHL) has a maximum of 12 doses.
• Treatment of previously untreated Systemic Anaplastic Large Cell Lymphoma (sALCL) or other CD30-expressing Peripheral T-Cell Lymphomas (PTCL) has a maximum of 8 doses.
• Treatment of Breast-Implant Associated Anaplastic Large Cell Lymphoma (ALCL) has a maximum of 6 cycles as adjuvant therapy.

II. Dosing Limits

1. Quantity Limit (max daily dose) [NDC Unit]:

• 50 mg vial: 4 vials per 21 days

2. Max Units (per dose and over time) [HCPCS Unit]:

• 200 billable units per 21 days

III. Initial Approval Criteria 

Coverage is provided in the following conditions:

• Patient is at least 18 years of age (unless otherwise specified); AND

Universal Criteria 

• Patient has CD30-positive disease; AND
• Patient must not be receiving concomitant bleomycin; AND
• Patient does not have severe renal impairment (i.e., CrCl <30 mL/min); AND
• Patient does not have moderate or severe hepatic impairment (Child-Pugh B or C); AND

Adult Classic Hodgkin Lymphoma (cHL) † Ф 

• • Used as single agent therapy; AND
    • Used as consolidation/maintenance therapy post-autologous hematopoietic stem cell transplant (auto-HSCT) in patients at high risk* for relapse or progression † ‡; OR
    • Patient has relapsed disease after failure of auto-HSCT or after failure of at least 2 prior multi-agent chemotherapy regimens in patients who are not auto-HSCT candidates †; OR
    • Used as subsequent systemic therapy (if not previously used) for relapsed or refractory disease ‡; OR
    • Used as palliative therapy for relapsed or refractory disease in patients >60 years of age ‡; OR
  • Used in combination with bendamustine; AND
    • Used as subsequent systemic therapy (if not previously used) for relapsed or refractory disease ‡: OR
• Used in combination with nivolumab; AND

• Used as subsequent systemic therapy (if not previously used) for relapsed or refractory disease ‡; OR
  • Used in combination with dacarbazine; AND
    • Used as primary treatment in patients > 60 years of age with stage I-II unfavorable or stage III-IV disease ‡; OR
  • Used in combination with doxorubicin, vinblastine, and dacarbazine (AVD); AND
    • Used as initial therapy for previously untreated stage III or IV disease †; OR
    • Used as initial therapy for previously untreated stage I or II unfavorable disease in patients >60 years of age ‡

Pediatric Classic Hodgkin Lymphoma (cHL) ‡ Ф 

• Patient is ≤18 years of age; AND
• Patient has relapsed or refractory disease; AND
  • • Used as re-induction or subsequent therapy; AND

• • • Used in combination with bendamustine, nivolumab, or gemcitabine; AND
      • Used in heavily pretreated patients with platinum or anthracycline-based chemotherapy; OR
      • Used if a decrease in cardiac function is observed; OR

• • • Used as maintenance therapy following high-dose therapy and autologous stem cell rescue (HDT/ASCR); AND

• • • Used as a single agent in high-risk patients (i.e., progressive disease, refractory disease, or relapse within 1 year of original diagnosis)

T-Cell Lymphomas 

• • Peripheral T-Cell Lymphoma (PTCL)
    • Used as a single agent after failure of at least one prior chemotherapy regimen for one of the following:
      • • •  
      • Systemic Anaplastic Large Cell Lymphoma (sALCL) † Ф
      • Peripheral T-Cell Lymphoma (PTCL) not otherwise specified ‡ Ф
      • Angioimmunoblastic T-cell Lymphoma (AITL) ‡ Ф; OR
    • Used in combination with cyclophosphamide, doxorubicin, and prednisone (CHP) as initial therapy for previously untreated:
      • • •  
      • Systemic Anaplastic Large Cell Lymphoma (sALCL) † Ф
      • Peripheral T-Cell Lymphoma (PTCL) not otherwise specified † Ф
      • Angioimmunoblastic T-cell Lymphoma (AITL) † Ф
      • Enteropathy-associated T-cell lymphoma Ф, monomorphic epitheliotropic intestinal T-cell lymphoma, nodal peripheral T-cell lymphoma with TFH phenotype, or follicular T-cell lymphoma ‡
  • Breast-Implant Associated Anaplastic Large Cell Lymphoma (ALCL) ‡
    • Used as adjuvant therapy as a single agent or in combination with cyclophosphamide, doxorubicin, and prednisone (CHP); AND

• • • Patient has localized disease to the capsule, implant, or breast with either lymph node involvement or radiation therapy is not feasible; OR
    • Patient has extended disease (stage II-IV); OR

• • • Used as subsequent therapy for relapsed or refractory as a single agent
  • Adult T-Cell Leukemia/Lymphoma ‡ Ф
    • Used as a single agent for acute or lymphoma subtypes; AND

• • • Used as subsequent therapy for non-responders to first-line therapy; OR

• • Used in combination with cyclophosphamide, doxorubicin, and prednisone (CHP); AND
    • Used as first-line therapy or continued treatment in responders to first-line therapy for acute or lymphoma subtypes; OR
    • Used as subsequent therapy for non-responders to first-line therapy for chronic or smoldering disease

• • Extranodal NK/T-Cell Lymphoma (Nasal type) ‡ Ф
    • Used as a single agent for relapsed or refractory disease; AND
    • Patient has previously received at least 2 different prior lines of therapy including an asparaginase based combination chemotherapy regimen
  • Hepatosplenic Gamma-Delta T-Cell Lymphoma ‡
    • Used as single-agent therapy; AND
      • Used for refractory disease as subsequent therapy after progression on two primary treatment regimens; OR
    • Used in combination with cyclophosphamide, doxorubicin, and prednisone (CHP); AND
      • Used as primary treatment or as an alternate induction regimen if not used during primary treatment

Primary Cutaneous Lymphomas 

• • Mycosis Fungoides (MF) † Ф/Sezary Syndrome (SS) ‡
    • Used as a single agent; AND
      • Used as primary therapy (excluding patients with stage IA-IIA MF with B1 blood involvement); OR
      • Used as subsequent therapy (excluding patients with relapsed or persistent stage IA-IIA MF with B1 blood involvement)

• • Primary Cutaneous CD30+ T-Cell Lymphoproliferative Disorders ‡ Ф
    • Used as a single agent; AND

• • • Patient has primary cutaneous anaplastic large cell lymphoma (pcALCL) †; OR
    • Patient has cutaneous ALCL with regional node (N1) (excludes systemic ALCL); OR
    • Patient has lymphomatoid papulosis (LyP) with extensive lesions that is relapsed or refractory to treatment options (e.g., clinical trial, observation, retreatment with primary treatment, or treatment with alternative regimen); OR

• • Used in combination with cyclophosphamide, doxorubicin, and prednisone (CHP); AND
    • Patient has cutaneous ALCL with regional node (N1) (excludes systemic ALCL)

B-Cell Lymphomas ‡ 

• • Diffuse Large B-Cell Lymphoma (DLBCL) or High Grade B-Cell Lymphoma
    • Used as subsequent therapy for partial response, no response, relapsed, progressive, or refractory disease in non-candidates for transplant
  • AIDS-related DLBCL, primary effusion lymphoma, or HHV8-positive DLBCL, not otherwise specified
    • Used as subsequent therapy for relapsed disease in non-candidates for transplant
  • Monomorphic Post-Transplant Lymphoproliferative Disorders (PTLD)
    • Used as subsequent therapy for patients with partial response, persistent disease, or progressive disease after receiving chemoimmunotherapy (e.g., RCHOP, etc.) as first-line treatment for B-cell type disease; OR
    • Used in combination with CHP (cyclophosphamide, doxorubicin, prednisone) for T-cell type disease

• • Histologic transformation of Follicular Lymphoma or Nodal Marginal Zone Lymphoma to Diffuse Large B-Cell Lymphoma (DLBCL)
    • Patient has received multiple lines of chemoimmunotherapy (e.g., BR, RCHOP, etc.) for transformed or indolent disease

† FDA Approved Indication(s); ‡ Compendia Recommended Indication(s); Ф Orphan Drug

IV. Renewal Criteria 

Coverage can be renewed based on the following criteria:

• Patient continues to meet universal and other indication-specific relevant criteria such as concomitant therapy requirements (not including prerequisite therapy), performance status, etc. identified in section III; AND
• Disease response with treatment defined by stabilization of disease or decrease in size of tumor or tumor spread; AND
• Absence of unacceptable toxicity from the drug. Examples of unacceptable toxicity include: progressive multifocal leukoencephalopathy, peripheral neuropathy, anaphylaxis and infusion reactions, hematologic toxicities (thrombocytopenia, neutropenia, and anemia), serious infections, opportunistic infections, tumor lysis syndrome, hepatotoxicity, pulmonary toxicity, serious dermatologic reactions, gastrointestinal complications, uncontrolled hyperglycemia, etc.

V. Dosage/Administration 

VI. Billing Code/Availability Information

HCPCS Code:

• J9042 - Injection, brentuximab vedotin, 1 mg; 1 billable unit = 1 mg

NDC:

• Adcetris single-use vial; 50 mg powder for injection: 51144-0050-xx

VII. References

1. Adcetris [package insert]. Bothell, WA; Seattle Genetics, Inc; October 2019.  Accessed October 2020.
2. Referenced with permission from the NCCN Drugs & Biologics Compendium (NCCN Compendium®) for brentuximab vedotin. National Comprehensive Cancer Network, 2020.  The NCCN Compendium® is a derivative work of the NCCN Guidelines®. NATIONAL COMPREHENSIVE CANCER NETWORK®, NCCN®, and NCCN GUIDELINES® are trademarks owned by the National Comprehensive Cancer Network, Inc. To view the most recent and complete version of the Compendium, go online to NCCN.org. Accessed October 2020.
3. Referenced with permission from the NCCN Drugs & Biologics Compendium (NCCN Compendium^®) T-Cell Lymphomas. Version 1.2021.  National Comprehensive Cancer Network, 2020. The NCCN Compendium^® is a derivative work of the NCCN Guidelines^®. NATIONAL COMPREHENSIVE CANCER NETWORK^®, NCCN^®, and NCCN GUIDELINES® are trademarks owned by the National Comprehensive Cancer Network, Inc. To view the most recent and complete version of the Compendium, go online to NCCN.org. Accessed October 2020.
4. Referenced with permission from the NCCN Drugs & Biologics Compendium (NCCN Compendium^®) Hodgkin Lymphoma. Version 2.2020.  National Comprehensive Cancer Network, 2020. The NCCN Compendium^® is a derivative work of the NCCN Guidelines^®. NATIONAL COMPREHENSIVE CANCER NETWORK^®, NCCN^®, and NCCN GUIDELINES® are trademarks owned by the National Comprehensive Cancer Network, Inc. To view the most recent and complete version of the Compendium, go online to NCCN.org. Accessed October 2020.
5. Duvoc M, Tetzlaff MT, Gangar P, et al. Results of a Phase II trial of brentuximab vedotin for CD20+ cutaneous T-cell lymphoma and lymphomatoid papulosis. J Clin Oncol 2015; 33:3759-65.
6. Horwitz SM, Advani RH, Bartlett NL, et al. Objective responses in relapsed T-cell lymphomas with single-agent brentuximab vedotin. Blood 2014;123:3095-3100.
7. Alderuccio, JP., Desai, A., Yepes, M.M., et al. Frontline brentuximab vedotin in breast implant-associated anaplastic large-cell lymphoma. Clin Case Rep 2018;, 6(4): 634-637. doi:10.1002/ccr3.1382.
8. Fahrenbruch R, Kintzel P, Bott AM, et al. Dose Rounding of Biologic and Cytotoxic Anticancer Agents: A Position Statement of the Hematology/Oncology Pharmacy Association. J Oncol Pract. 2018 Mar;14(3):e130-e136.
9. Hematology/Oncology Pharmacy Association (2019). Intravenous Cancer Drug Waste Issue Brief. Retrieved from http://www.hoparx.org/images/hopa/advocacy/Issue-Briefs/Drug_Waste_2019.pdf
10. Bach PB, Conti RM, Muller RJ, et al. Overspending driven by oversized single dose vials of cancer drugs. BMJ. 2016 Feb 29;352:i788.
11. Referenced with permission from the NCCN Drugs & Biologics Compendium (NCCN Compendium^®) B-Cell Lymphomas. Version 4.2020.  National Comprehensive Cancer Network, 2020. The NCCN Compendium^® is a derivative work of the NCCN Guidelines^®. NATIONAL COMPREHENSIVE CANCER NETWORK^®, NCCN^®, and NCCN GUIDELINES® are trademarks owned by the National Comprehensive Cancer Network, Inc. To view the most recent and complete version of the Compendium, go online to NCCN.org. Accessed October 2020.
12. Connors JM, Jurczak W, Straus DJ, et al. Brentuximab Vedotin with Chemotherapy for Stage III or IV Hodgkin's Lymphoma [published correction appears in N Engl J Med. 2018 Mar 1;378(9):878]. N Engl J Med. 2018;378(4):331-344.
13. 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;385(9980):1853-1862.
14. Younes A, Gopal AK, Smith SE, et al. Results of a pivotal phase II study of brentuximab vedotin for patients with relapsed or refractory Hodgkin's lymphoma. J Clin Oncol. 2012;30(18):2183-2189.
15. Horwitz S, O'Connor OA, Pro B, et al. Brentuximab vedotin with chemotherapy for CD30-positive peripheral T-cell lymphoma (ECHELON-2): a global, double-blind, randomised, phase 3 trial. Lancet. 2019;393(10168):229-240.
16. 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(18):2190-2196.
17. Prince HM, Kim YH, Horwitz SM, et al. Brentuximab vedotin or physician's choice in CD30-positive cutaneous T-cell lymphoma (ALCANZA): an international, open-label, randomised, phase 3, multicentre trial. Lancet. 2017;390(10094):555-566.

18. Cole PD, McCarten KM, Pei Q, et al. Brentuximab vedotin with gemcitabine for paediatric and young adult patients with relapsed or refractory Hodgkin's lymphoma (AHOD1221): a Children's Oncology Group, multicentre single-arm, phase 1-2 trial. Lancet Oncol. 2018 Sep;19(9):1229-1238. doi: 10.1016/S1470-2045(18)30426-1. Epub 2018 Aug 16.
19. Palmetto GBA. Local Coverage Article (LCA): Billing and Coding: Chemotherapy (A56141). Centers for Medicare & Medicaid Services, Inc. Updated on 05/26/2020 with effective date 04/30/2020. Accessed October 2020.

Appendix 1 – Covered Diagnosis Codes

Appendix 2 – Centers for Medicare and Medicaid Services (CMS)

Medicare coverage for outpatient (Part B) drugs is outlined in the Medicare Benefit Policy Manual (Pub. 100-2), Chapter 15, §50 Drugs and Biologicals. In addition, National Coverage Determination (NCD), Local Coverage Determinations (LCDs), and Local Coverage Articles (LCAs) may exist and compliance with these policies is required where applicable. They can be found at: http://www.cms.gov/medicare-coverage-database/search/advanced-search.aspx. Additional indications may be covered at the discretion of the health plan.

Medicare Part B Covered Diagnosis Codes (applicable to existing NCD/LCD/LCA):