Last Review Date: 06/01/2021

Date of Origin: 02/23/2016

Dates Reviewed: 02/2016, 12/2016, 02/2017, 05/2017, 06/2017, 11/2017, 02/2018, 05/2018, 06/2018, 09/2018, 12/2018, 03/2019, 06/2019, 08/2019, 10/2019, 12/2019, 03/2020, 06/2020, 09/2020, 12/2020, 03/2021, 06/2021

1. Length of Authorization ^1,6,16,17

Coverage will be provided for six 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).

2. Dosing Limits

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

• Darzalex 100 mg single-dose vial for injection: Up to 3 vials per dose

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

• Darzalex 400 mg single-dose vial for injection: Up to 4 vials per dose

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

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

• Up to 180 billable units per dose
  • • • Weekly Week 1 to 8, then every two weeks, Week 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

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

Multiple Myeloma † Ф ^{1-11,13,14,16,17,18}   

• 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 for relapsed or progressive disease 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 after at least two prior therapies including an immunomodulatory agent (e.g., lenalidomide, 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 ‡ ^2,12,15

• Used as single agent therapy; AND
• Used for the treatment of relapsed/refractory disease

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

4. Renewal Criteria ^{1,2,3,6,16,17}

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 or decrease in size of tumor or tumor spread; AND
• Absence of unacceptable toxicity from the drug. Examples of unacceptable toxicity include: severe infusion reactions including anaphylactic reactions, neutropenia, thrombocytopenia, etc.; AND
  • 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).

5. Dosage/Administration ^1,3,5,12,18

6. Billing Code/Availability Information

HCPCS Code:

• J9145 – Injection, daratumumab, 10 mg; 1 billable unit = 10 mg

NDC(s):

• Darzalex 100 mg/5 mL single-dose vial: 57894-0502-xx
• Darzalex 400 mg/20 mL single-dose vial: 57894-0502-xx

7. References

1. Darzalex [package insert]. Horsham, PA; Janssen Biotech, Inc; March 2021. Accessed April 2021.
2. Referenced with permission from the NCCN Drugs & Biologics Compendium (NCCN Compendium®) for daratumumab. 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 April 2021.
3. 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.
4. 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.
5. 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.
6. 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.

7. 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.
8. 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.
9. 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.
10. 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.
11. 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.
12. 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.

13. 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.
14. 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 April 2021.
15. Referenced with permission from the NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines®) for Systemic Light Chain Amyloidosis 2.2021. 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 April 2021.
16. 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.
17. 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.
18. Gasparetto C, Lentzsch S, Schiller G, et al. Selinexor, daratumumab, and dexamethasone in patients with relapsed or refractory multiple myeloma. eJHaem. 2020;1-10. https://doi.org/10.1002/jha2.122

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