Last Review Date: 08/03/2021

Date of Origin: 06/02/2020

Dates Reviewed: 06/2020, 09/2020, 01/2021, 02/2021, 08/2021

1. Length of Authorization ^1,9,19,20

Coverage will be provided for 6 months and may be renewed unless otherwise specified.   

• Use for newly diagnosed multiple myeloma in combination with bortezomib, thalidomide, and dexamethasone may not be renewed.
• Use for newly diagnosed disease in combination with bortezomib, lenalidomide and dexamethasone may be renewed for up to a maximum of 2 years of maintenance therapy.
• Use for newly diagnosed or relapsed disease in combination with cyclophosphamide, bortezomib and dexamethasone may be renewed for up to a maximum of 80 weeks (32 weeks of induction therapy and 48 weeks of maintenance therapy).
• Use for newly diagnosed systemic light chain amyloidosis in combination with bortezomib, cyclophosphamide and dexamethasone may be renewed for up to a maximum of 2 years.

2. Dosing Limits

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

• Darzalex Faspro 1,800 mg/30,000 unit single-dose vial for injection: 1 vial per dose

• Weekly Weeks 1 to 8, then every two weeks Weeks 9-24, then every four weeks Week 25 onwards

2. Max Units (per dose and over time) [HCPCS Unit]:
   • Up to 180 billable units per dose

• Weekly Weeks 1 to 8, then every two weeks Weeks 9-24, then every four weeks Week 25 onwards

3. Initial Approval Criteria ¹

Coverage is provided in the following conditions:

• Patient is at least 18 years of age; AND

Universal Criteria ¹

• Therapy will not be used in combination with other anti-CD38 therapies (i.e., daratumumab, isatuximab, etc.); AND

Multiple Myeloma † Ф ^{1,2,6-14,16,17,19,20}                              

• Used in the treatment of newly diagnosed disease in patients who are ineligible for autologous stem cell transplant (ASCT) in combination with ONE of the following regimens:
  • Lenalidomide and dexamethasone; OR
  • Bortezomib, melphalan and prednisone; OR
  • Cyclophosphamide, bortezomib, and dexamethasone; OR
• Used in the treatment of newly diagnosed disease in patients who are eligible for autologous stem cell transplant (ASCT) in combination with ONE of the following regimens:
  • Bortezomib, lenalidomide, and dexamethasone; OR
  • Bortezomib, thalidomide, and dexamethasone (VTd); OR
  • Cyclophosphamide, bortezomib, and dexamethasone; OR
• Used for disease relapse after 6 months following primary induction therapy with the same regimen in combination with ONE of the following regimens:
  • Lenalidomide and dexamethasone for non-transplant candidates; OR
  • Cyclophosphamide, bortezomib, and dexamethasone; OR
• Used as subsequent therapy in combination with dexamethasone and ONE of the following:
  • Lenalidomide; OR
  • Bortezomib; OR
  • Carfilzomib; OR
  • Cyclophosphamide and bortezomib; OR
  • Selinexor; OR
• Used in combination with pomalidomide and dexamethasone; AND
  • Used after at least ONE prior line of therapy including lenalidomide and a proteasome inhibitor (bortezomib, carfilzomib, etc.); OR
  • Used after at least TWO prior therapies including an immunomodulatory agent (e.g., pomalidomide, etc.) and a proteasome inhibitor (bortezomib, carfilzomib, etc.); OR
• Used as single agent therapy; AND
  • Patient received at least three prior lines of therapy including a proteasome inhibitor (e.g., bortezomib, carfilzomib, etc.) and an immunomodulatory agent (e.g., lenalidomide, pomalidomide, etc.); OR
  • Patient is double-refractory to a proteasome inhibitor and an immunomodulatory agent

Systemic Light Chain Amyloidosis † ‡ ^1,2,15,18,21

• Patient must NOT have NYHA Class IIIB or Class IV, or Mayo Stage IIIB cardiac disease; AND
  • Used in combination with bortezomib, cyclophosphamide and dexamethasone (D-VCd) for newly diagnosed disease; OR
  • Used as single agent therapy for the treatment of relapsed/refractory disease

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

4. Renewal Criteria ^{1,2,6,9,19,20}

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
• Disease response with treatment as defined by stabilization of disease and decrease in size of tumor of tumor spread; AND
• Absence of unacceptable toxicity from the drug. Examples of unacceptable toxicity include: hypersensitivity and other administration reactions (e.g., systemic administration-related reactions, local injection-site reactions, etc.), neutropenia, thrombocytopenia, cardiac toxicity, etc.; AND

Multiple Myeloma

• Use for newly diagnosed disease in combination with bortezomib, thalidomide and dexamethasone after 24 weeks of induction/consolidation therapy may not be renewed.
• Use for newly diagnosed disease in combination with bortezomib, lenalidomide and dexamethasone may be renewed for up to a maximum of 2 years of maintenance therapy.
• Use for newly diagnosed or relapsed disease in combination with cyclophosphamide, bortezomib and dexamethasone may be renewed for up to a maximum of 80 weeks (32 weeks of induction therapy and 48 weeks of maintenance therapy).

Systemic Light Chain Amyloidosis (newly diagnosed disease)

• Use for newly diagnosed disease in combination with bortezomib, cyclophosphamide and dexamethasone (D-VCd) may be renewed for a maximum of 2 years of therapy.

5. Dosage/Administration ^1,6,8,15

6. Billing Code/Availability Information

HCPCS Code:

• J9144 - Injection, daratumumab, 10 mg and hyaluronidase-fihj; 1 billable unit=10 mg

NDC:

• Darzalex Faspro 1,800 mg of daratumumab and 30,000 units of hyaluronidase per 15 mL single-dose vial: 57894-0503-xx

7. References

1. Darzalex Faspro [package insert]. Horsham, PA; Janssen Biotech, Inc; July 2021. Accessed July 2021.
2. Referenced with permission from the NCCN Drugs & Biologics Compendium (NCCN Compendium®) for daratumumab and hyaluronidase-fihj. National Comprehensive Cancer Network, 2021. 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 July 2021.
3. Chari A, San Miguel J, McCarthy H, et al. Subcutaneous Daratumumab Plus Standard Treatment Regimens in Patients with Multiple Myeloma across Lines of Therapy: Pleiades Study Update. Blood (2019) 134 (Supplement_1): 3152.
4. Mateos MV, Nahi H, Legier W, et al. Efficacy and safety of the randomized, open-label, non-inferiority, phase 3 study of subcutaneous (SC) versus intravenous (IV) daratumumab (DARA) administration in patients (pts) with relapsed or refractory multiple myeloma (RRMM): COLUMBA. JCO 2019 37:15_suppl, 8005-8005.
5. Lancman G, Arinsburg S, Jhang J, et al. Blood Transfusion Management for Patients Treated With Anti-CD38 Monoclonal Antibodies. Front. Immunol.9:2616. Doi: 10.3389/fimmu.2018.02616.
6. Chari A, Martinez-Lopez J, Mateos MV, et al. Daratumumab plus carfilzomib and dexamethasone in patients with relapsed or refractory multiple myeloma. Blood. 2019 Aug 1;134(5):421-431. doi: 10.1182/blood.2019000722. Epub 2019 May 21.
7. Facon T, Kumar S, Plesner T, et al. Daratumumab plus Lenalidomide and Dexamethasone for Untreated Myeloma. N Engl J Med. 2019 May 30;380(22):2104-2115. doi: 10.1056/NEJMoa1817249.
8. Mateos MV, Dimopoulos MA, Cavo M, et al. Daratumumab plus Bortezomib, Melphalan, and Prednisone for Untreated Myeloma. N Engl J Med. 2018 Feb 8;378(6):518-528. doi: 10.1056/NEJMoa1714678. Epub 2017 Dec 12.
9. Moreau P, Attal M, Hulin C, et al. Bortezomib, thalidomide, and dexamethasone with or without daratumumab before and after autologous stem-cell transplantation for newly diagnosed multiple myeloma (CASSIOPEIA): a randomised, open-label, phase 3 study. Lancet. 2019 Jul 6;394(10192):29-38. doi: 10.1016/S0140-6736(19)31240-1. Epub 2019 Jun 3.
10. Dimopoulos MA, Oriol A, Nahi H, et al. Daratumumab, Lenalidomide, and Dexamethasone for Multiple Myeloma. N Engl J Med. 2016 Oct 6;375(14):1319-1331.
11. Palumbo A, Chanan-Khan A, Weisel K, et al. Daratumumab, Bortezomib, and Dexamethasone for Multiple Myeloma. N Engl J Med. 2016 Aug 25;375(8):754-66. doi: 10.1056/NEJMoa1606038.
12. Chari A, Suvannasankha A, Fay JW, et al. Daratumumab plus pomalidomide and dexamethasone in relapsed and/or refractory multiple myeloma. Blood. 2017 Aug 24;130(8):974-981. doi: 10.1182/blood-2017-05-785246. Epub 2017 Jun 21.
13. Lonial S, Weiss BM, Usmani SZ, et al. Daratumumab monotherapy in patients with treatment-refractory multiple myeloma (SIRIUS): an open-label, randomised, phase 2 trial. Lancet. 2016 Apr 9;387(10027):1551-1560. doi: 10.1016/S0140-6736(15)01120-4. Epub 2016 Jan 7.
14. Lokhorst HM, Plesner T, Laubach JP, et al. Targeting CD38 with Daratumumab Monotherapy in Multiple Myeloma. N Engl J Med. 2015 Sep 24;373(13):1207-19. doi: 10.1056/NEJMoa1506348. Epub 2015 Aug 26.
15. Kaufman GP, Schrier SL, Lafayette RA, et al. Daratumumab yields rapid and deep hematologic responses in patients with heavily pretreated AL amyloidosis. Blood. 2017 Aug 17;130(7):900-902. doi: 10.1182/blood-2017-01-763599. Epub 2017 Jun 14.
16. Dimopoulous M, Quach H, Mateos MV, et al. Carfilzomib, dexamethasone, and daratumumab versus carfilzomib and dexamethasone for patients with relapsed or refractory multiple myeloma (CANDOR): results from a randomised, multicentre, open-label, phase 3 study. Lancet. 2020 July 18;396(10245):186-197.
17. Referenced with permission from the NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines®) for Multiple Myeloma Version 7.2021. National Comprehensive Cancer Network, 2021. 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 July 2021.
18. Referenced with permission from the NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines®) for Systemic Light Chain Amyloidosis Version 1.2022. National Comprehensive Cancer Network, 2021. 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 July 2021.
19. Voorhees PM, Kaufman JL, Laubach J, et al. Daratumumab, lenalidomide, bortezomib, and dexamethasone for transplant-eligible newly diagnosed multiple myeloma: the GRIFFIN trial. Blood. 2020 Aug 20;136(8):936-945.
20. Yimer H, Melear J, Faber E, et al. Daratumumab, bortezomib, cyclophosphamide and dexamethasone in newly diagnosed and relapsed multiple myeloma: LYRA study. Br J Haematol. 2019 May;185(3):492-502.
21. Palladini G, Kastritis E, Maurer M, et al Daratumumab plus CyBorD for patients with newly diagnosed AL amyloidosis: safety run-in results of ANDROMEDA. Blood 2020 Jul 2;136(1):71-80. doi: 10.1182/blood.2019004460.
22. Dimopoulos MA, Terpos E, Boccadoro M, et al; APOLLO Trial Investigators. Daratumumab plus pomalidomide and dexamethasone versus pomalidomide and dexamethasone alone in previously treated multiple myeloma (APOLLO): an open-label, randomised, phase 3 trial. Lancet Oncol. 2021 Jun;22(6):801-812. doi: 10.1016/S1470-2045(21)00128-5.

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): N/A