Last Review Date: 09/05/2024

Date of Origin: 07/01/2020

Dates Reviewed: 07/2020, 07/2021, 09/2021, 07/2022, 07/2023, 09/2024

1. Length of Authorization

Conditioning Treatment: Coverage is provided for 6 months and may NOT be renewed.

All Other Indications: Coverage is provided for 6 months and may be renewed.

2. Dosing Limits

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

• Evomela 50 mg single-dose vial for reconstitution: 10 vials

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

• Conditioning Treatment: 250 billable units for 2 doses only prior to ASCT
• All Other Indications: 50 billable units every 14 days for 4 doses, then 50 billable units every 28 days thereafter

3. Initial Approval Criteria ¹

Coverage is provided in the following conditions:

• Patient is at least 18 years of age; AND

Universal Criteria ¹

• Patient does not have a history of serious allergic reactions to melphalan; AND
• Patient must have had an intolerance to melphalan (Alkeran®) IV prior to consideration of Evomela®; AND

Multiple Myeloma (MM) † ^1,2,7

• Used as high-dose myeloablative conditioning treatment † Ф; AND
  • Patient will receive an autologous stem cell transplant (ASCT); OR

• Used as primary therapy for symptomatic disease in non-transplant candidates ‡; AND
  • Used in combination with daratumumab, bortezomib, and prednisone; AND
  • Patient is unable to tolerate oral melphalan therapy; OR
• Used for the management of POEMS (polyneuropathy, organomegaly, endocrinopathy, monoclonal protein, skin changes) syndrome ‡; AND
  • Used in combination with dexamethasone; AND
  • Patient is unable to tolerate oral melphalan therapy; AND
    • Patient is transplant ineligible; OR
    • Patient is transplant eligible and used as induction therapy

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

4. Renewal Criteria ¹

Coverage can be renewed based upon 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
• Absence of unacceptable toxicity from the drug. Examples of unacceptable toxicity include: severe gastrointestinal toxicity (e.g., nausea, vomiting, diarrhea, mucositis), severe hepatotoxicity, severe bone marrow suppression, hypersensitivity reactions, secondary malignancies (e.g., myeloproliferative syndrome, acute leukemia), etc.; AND

Conditioning Treatment

• Coverage cannot be renewed.

All Other Indications

• Disease response with treatment as defined by stabilization of disease or decrease in size of tumor or tumor spread

5. Dosage/Administration ¹

6. Billing Code/Availability Information

HCPCS Code:

• J9246 - Injection, melphalan (evomela), 1 mg; 1 billable unit = 1 mg

NDC:

• Evomela 50 mg lyophilized powder in single-dose vial for reconstitution: 72893-0001-xx

7. References

1. Evomela [package insert]. East Windsor, NJ; Acrotech Biopharma, LLC.; April 2022. Accessed August 2024.
2. Referenced with permission from the NCCN Drugs & Biologics Compendium (NCCN Compendium®) for Evomela®. National Comprehensive Cancer Network, 2024. 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 August 2024.
3. Aljitawi OS, Ganguly S, Abhyankar SH, et al. Phase IIa cross-over study of propylene glycol-free melphalan (LGD-353) and Alkeran in multiple myeloma autologous transplantation. Bone Marrow Transplant. 2014;49(8):1042-1045
4. Hari P, Aljitawi OS, Arce-Lara C, et al. A phase IIb, multicenter, open-label, safety, and efficacy study of high-dose, propylene glycol-free melphalan hydrochloride for injection (EVOMELA) for myeloablative conditioning in multiple myeloma patients undergoing autologous transplantation. Biol Blood Marrow Transplant. 2015;21(12):2100-2105.
5. Mai EK, Benner A, Bertsch U, et al. Single Versus Tandem High-Dose Melphalan Followed by Autologous Blood Stem Cell Transplantation in Multiple Myeloma: Long-Term Results From the Phase III GMMG-HD2 Trial. Br J Haematol. 2016 Jun;173(5):731-41.  doi: 10.1111/bjh.13994.
6. Moreau P, Facon T, Attal M, et al. Comparison of 200 mg/m(2) Melphalan and 8 Gy Total Body Irradiation Plus 140 mg/m(2) Melphalan as Conditioning Regimens for Peripheral Blood Stem Cell Transplantation in Patients With Newly Diagnosed Multiple Myeloma: Final Analysis of the Intergroupe Francophone Du Myélome 9502 Randomized Trial. Blood. 2002 Feb 1;99(3):731-5. doi: 10.1182/blood.v99.3.731.
7. Referenced with permission from the NCCN Drugs & Biologics Compendium (NCCN Compendium®) Multiple Myeloma Version 4.2024. National Comprehensive Cancer Network, 2024. 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 August 2024.
8. Li J, Zhang W, Jiao L, Duan MH, Guan HZ, Zhu WG, Tian Z, Zhou DB. Combination of melphalan and dexamethasone for patients with newly diagnosed POEMS syndrome. Blood. 2011 Jun 16;117(24):6445-9. doi: 10.1182/blood-2010-12-328112. 
9. Dispenzieri A. POEMS Syndrome: 2019 Update on diagnosis, risk-stratification, and management. Am J Hematol 2019;94:812-827. Doi: 10.1002/ajh.25495.
10. Referenced with permission from the NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines®) for Melphalan: Multiple Myeloma Order Template, MUM76. National Comprehensive Cancer Network, 2024. 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 Guidelines, go online to NCCN.org. Accessed August 2024.

Appendix 1 – Covered Diagnosis Codes

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

The preceding information is intended for non-Medicare coverage determinations. 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 Determinations (NCDs) and/or Local Coverage Determinations (LCDs) may exist and compliance with these policies is required where applicable. Local Coverage Articles (LCAs) may also exist for claims payment purposes or to clarify benefit eligibility under Part B for drugs which may be self-administered. The following link may be used to search for NCD, LCD, or LCA documents: https://www.cms.gov/medicare-coverage-database/search.aspx. Additional indications, including any preceding information, may be applied at the discretion of the health plan.

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