Last Review Date: 05/02/2024

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, 12/2021, 03/2022, 06/2022, 09/2022, 12/2022, 03/2023, 06/2023, 09/2023, 12/2023, 03/2024, 05/2024

1. Length of Authorization ^{1,16,17,19,21,24}

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 multiple myeloma 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 or refractory/progressive multiple myeloma 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 multiple myeloma in combination with carfilzomib, lenalidomide, and dexamethasone may be renewed for up to a maximum of 32 weeks.
• Use as maintenance therapy for multiple myeloma in combination with lenalidomide may be renewed for up to a maximum of 2 years.
• Use for pediatric acute lymphoblastic leukemia may not be renewed.

2. Dosing Limits

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

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

• Every 7 days for 12 doses, every 14 days for 8 doses, every 21 days for 16 doses, then every 28 days; OR

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

• Every 7 days for 12 doses, every 14 days for 8 doses, every 21 days for 16 doses, then every 28 days

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

Multiple Myeloma:

• 180 billable units every 7 days for 12 doses, every 14 days for 8 doses, every 21 days for 16 doses, then every 28 days

Systemic Light Chain Amyloidosis:

• 180 billable units every 7 days for 8 doses, every 14 days for 8 doses, then every 28 days

Pediatric ALL:

• 180 billable units every 7 days for 8 doses

3. Initial Approval Criteria ¹

Coverage is provided in the following conditions:

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

Universal Criteria

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

Multiple Myeloma † ‡ Ф ^{1-11,13,14,16-19,22,23}        

• 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
  • Carfilzomib, lenalidomide, and dexamethasone (ixazomib may be substituted for carfilzomib); 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 refractory/progressive disease in combination with dexamethasone and ONE of the following:
  • Lenalidomide; OR
  • Bortezomib; OR
  • Carfilzomib; OR
  • Cyclophosphamide and bortezomib; OR
  • Selinexor; OR
  • Venetoclax (for patients with t(11:14) ONLY); OR
• Used in combination with pomalidomide and dexamethasone after prior therapy with lenalidomide 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; OR
  • Used as maintenance therapy for symptomatic disease in transplant candidates; AND
    • Used as single agent therapy or in combination with lenalidomide; AND
      • • • Used after response to primary myeloma therapy; OR
          • Used for response or stable disease following an autologous hematopoietic cell transplant (HCT); OR
          • Used for response or stable disease following a tandem autologous or allogeneic HCT for high risk* patients

*High-risk as defined by the Revised International Staging System for Multiple Myeloma is the presence of del(17p) and/or translocation t(4;14) and/or translocation t(14;16). This is not an all-inclusive list. Refer to the NCCN Multiple Myeloma Guidelines for additional risk factors.

Systemic Light Chain Amyloidosis ‡ ^{2,12,15,25-27}

• Used as single agent therapy; AND
  • Used for the treatment of relapsed/refractory disease; OR
  • Used for newly diagnosed disease; AND
    • Patient has significant neuropathy; OR
    • Patient has stage IIIb disease with no significant neuropathy

Pediatric Acute Lymphoblastic Leukemia (ALL) ‡ ^{2, 20,21}

• Patient age ≥ 1 and ≤ 30 years; AND
• Patient has relapsed/refractory T-cell ALL; AND
• Used in combination with vincristine, pegaspargase/calaspargase, doxorubicin, and prednisone/dexamethasone

† 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
• 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-related reactions including anaphylactic reactions, neutropenia, thrombocytopenia, etc.; AND

Multiple Myeloma ^{1,16,17,19,24}

• Use for newly diagnosed disease 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 or refractory/progressive 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 disease in combination with carfilzomib, lenalidomide, and dexamethasone may be renewed for up to a maximum of 32 weeks.
• Use as maintenance therapy in combination with lenalidomide may be renewed for up to a maximum of 2 years.

Pediatric Acute Lymphoblastic Leukemia ²¹

• May not be renewed

5. Dosage/Administration ^{1,12,16-19,21,23,24,27}

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 100 mg/5mL single-dose vial: 57894-0505-xx
• Darzalex 400 mg/20 mL single-dose vial: 57894-0502-xx
• Darzalex 400 mg/20 mL single-dose vial: 57894-0505-xx

7. References

1. Darzalex [package insert]. Horsham, PA; Janssen Biotech, Inc; January 2023. Accessed April 2024.
2. Referenced with permission from the NCCN Drugs & Biologics Compendium (NCCN Compendium®) for daratumumab. 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 April 2024.
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 3.2024. 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 April 2024.
15. Referenced with permission from the NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines®) for Systemic Light Chain Amyloidosis 2.2024. 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 April 2024.
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.
19. Landgren O, Hultcrantz M, Diamond B, et al. Safety and Effectiveness of Weekly Carfilzomib, Lenalidomide, Dexamethasone, and Daratumumab Combination Therapy for Patients With Newly Diagnosed Multiple Myeloma: The MANHATTAN Nonrandomized Clinical Trial. JAMA Oncol. 2021 Jun 1;7(6):862-868. doi: 10.1001/jamaoncol.2021.0611.
20. Referenced with permission from the NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines®) for Pediatric Acute Lymphoblastic Leukemia Version 5.2024. 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 April 2024.
21. Hogan LE, Bhatla T, Teachey DT, et al. Efficacy and safety of daratumumab (DARA) in pediatric and young adult patients (pts) with relapsed/refractory T-cell acute lymphoblastic leukemia (ALL) or lymphoblastic lymphoma (LL): Results from the phase 2 DELPHINUS study. Journal of Clinical Oncology 2022;40:10001-10001.
22. Moreau P, Hulin C, Perrot A, et al. Maintenance with daratumumab or observation following treatment with bortezomib, thalidomide, and dexamethasone with or without daratumumab and autologous stem-cell transplant in patients with newly diagnosed multiple myeloma (CASSIOPEIA): an open-label, randomised, phase 3 trial. Lancet Oncol 2021;22:1378-1390.
23. Bahlis NJ, Baz R, Harrison SJ, et al. Phase I Study of Venetoclax Plus Daratumumab and Dexamethasone, With or Without Bortezomib, in Patients With Relapsed or Refractory Multiple Myeloma With and Without t(11;14). J Clin Oncol. 2021 Nov 10;39(32):3602-3612. doi: 10.1200/JCO.21.00443. Epub 2021 Aug 13. PMID: 34388020; PMCID: PMC8577687.
24. Laubach JP, Kaufman JL, Sborov DW, et al. Daratumumab (DARA) Plus Lenalidomide, Bortezomib, and Dexamethasone (RVd) in Patients (Pts) with Transplant-Eligible Newly Diagnosed Multiple Myeloma (NDMM): Updated Analysis of Griffin after 24 Months of Maintenance. Blood 2021; 138 (Supplement 1): 79. doi: https://doi.org/10.1182/blood-2021-149024.
25. Sanchorawala V, Boccadoro M, Gertz M, et al. Guidelines for high dose chemotherapy and stem cell transplantation for systemic AL amyloidosis: EHA-ISA working group guidelines. Amyloid 2022;29:1-7.
26. Wechalekar AD, Cibeira MT, Gibbs SD, et al. Guidelines for non-transplant chemotherapy for treatment of systemic AL amyloidosis: EHA-ISA working group. Amyloid 2023;30:3-17.
27. Kastritis E, Minnema MC, Dimopoulos MA, et al. Daratumumab Monotherapy in Previously Untreated High-Risk Patients with Stage 3B Light Chain (AL) Amyloidosis: A Phase II Multicenter Study By European Myeloma Network (EMN). Blood 2019; 134 (Supplement_1): 1868. doi: https://doi.org/10.1182/blood-2019-126524.

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