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Last Review Date: 07/02/2024

Date of Origin: 12/16/2014

Dates Reviewed: 12/2014, 09/2015, 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, 03/2021, 03/2022, 03/2023, 03/2024, 07/2024

1. Length of Authorization ^1,9-11

• Relapsed or refractory disease (single agent or with a TKI):

• Initial coverage will be provided for 30 weeks for a total of five cycles (2 cycles of induction followed by 3 cycles of consolidation)
• Continued coverage will be provided every 24 weeks for a maximum of two additional authorizations (4 cycles of continued therapy)

• Relapsed or refractory disease (as a component of COG ALL1331 regimen):

• Coverage will be provided every 56 days for a maximum of 3 cycles

• Consolidation therapy (single agent) (Adult and Pediatric):
  • Coverage will be provided for 42 days
• Consolidation therapy (in combination with TKI) (Adult):
  • Coverage will be provided for five 42-day cycles
• MRD+ or less than complete response to induction therapy (Pediatric):

• Coverage will be provided for 24 weeks for a total of four cycles (1 cycle of induction followed by 3 cycles of consolidation)

• Maintenance therapy (Adult):

• Coverage will be provided for up to 30 weeks for a total of five cycles (1-2 cycles of induction followed by 3 cycles of consolidation)

• Infant ALL in combination with an Interfant regimen:

• Coverage will be provided for 28 days

2. Dosing Limits

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

• Blincyto 35 mcg powder for injection: 28 vials per 42 day supply

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

• Acute Lymphoblastic Leukemia (ALL) (Adult/Pediatric)

Cycle 1 – 5 (Induction/Consolidation)

• 980 billable units per 42 days

Cycle 6 – 9 (Continued Therapy)

• 980 billable units per 84 days

3. Initial Approval Criteria ¹

Coverage is provided in the following conditions:

Universal Criteria ¹

• Patient has not received a live vaccine within 2 weeks prior to initiating therapy and will not receive concurrent treatment with lives vaccine while on therapy; AND

Acute Lymphoblastic Leukemia (ALL) – Adult † ‡ Ф ^1,2

• Patient is at least 18 years of age*; AND
• Patient has B-cell precursor ALL; AND
  • Patient has positive minimal residual disease (MRD+) greater than or equal to 0.1% †; AND
    • Used as a single agent for patients in first or second complete remission (CR); OR
  • Used as consolidation therapy; AND
    • Used as a single agent as part of multiphase chemotherapy for Philadelphia chromosome-negative (Ph-) disease †; OR
    • Patient has persistent/rising MRD; AND
      • Used with or without a tyrosine kinase inhibitor (TKI§) for Philadelphia chromosome-positive (Ph+) disease after CR to induction therapy; OR
      • Used as a single agent for Ph- disease; OR
    • Patient has negative minimal residual disease (MRD-); AND
      • Used with a TKI§ for Ph+ disease after CR to induction therapy in patients who are not candidates for multiagent therapy; OR
      • Used as a single agent for Ph+ disease; AND
        • Patient is refractory to TKIs; AND
        • Used as a component of inotuzumab ozogamicin + mini-hyperCVD regimen; OR
      • Used as a single agent for Ph- disease; AND
        • Patient is contraindicated to multiagent therapy; OR
    • Patient has MRD unavailable; AND
      • Used as a single agent for Ph- disease; AND
      • Patient is contraindicated to multiagent therapy; OR
  • Used as maintenance therapy; AND
    • Used as a single agent alternating with POMP (prednisone, vincristine, methotrexate, and mercaptopurine); AND
    • Patient has negative minimal residual disease (MRD-); AND
      • Patient has Ph+ disease; AND
        • Patient is refractory to TKIs; AND
        • Used following induction therapy with inotuzumab ozogamicin + mini-hyperCVD; OR
      • Patient has Ph- disease; AND
        • Used following induction therapy with Hyper-CVAD; OR
        • Used following induction therapy with inotuzumab ozogamicin + mini-hyperCVD; OR
  • Patient has relapsed or refractory disease; AND
    • Used with or without a TKI§ for Ph+ disease; OR
    • Used as a single agent for Ph- disease

*NCCN recommendations for ALL may be applicable to adolescent and young adult (AYA) patients within the age range of 15-39 years.

§TKI options include bosutinib, dasatinib, imatinib, nilotinib, or ponatinib.

Pediatric Acute Lymphoblastic Leukemia (ALL) † ‡ Ф ^1,2,6

• Patient is at least 1 month of age; AND
  • Used as a single agent; AND
    • Patient has B-cell precursor ALL; AND
      • Patient has minimal residual disease positive (MRD+) ALL †; AND
        • Patient is in first or second complete remission with MRD greater than or equal to 0.1%; OR
        • Used after consolidation therapy for Ph- or Ph-like disease; OR
      • Used for less than complete response at the end of consolidation therapy; AND
        • Patient has Ph+ disease; OR
      • Patient has relapsed or refractory disease †; AND
        • Patient has Ph- disease; OR
        • Patient has Ph+ disease intolerant/refractory to TKI; OR
      • Used in the consolidation phase of multiphase chemotherapy for Ph- disease †; OR
  • Used as a component of COG AALL1331 regimen; AND
    • Patient has B-cell precursor ALL; AND
    • Patient has relapsed or refractory disease; AND
      • Patient has Ph- disease; OR
      • Patient has Ph+ disease; AND
        • Used in combination with dasatinib or imatinib; OR
  • Used in combination with an interfant regimen (e.g., Interfant-06, Interfant-99, etc.) for infant ALL with KMT2A status (11q23) rearranged

*NCCN recommendations for Pediatric ALL may be applicable to certain adolescent and young adult (AYA) patients up to 30 years of age.

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

4. Renewal Criteria ^1,2,9-11

Coverage may be renewed based upon the following criteria:

• Patient continues to meet the 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: Cytokine Release Syndrome (CRS), neurological toxicities [including Immune Effector Cell-Associated Neurotoxicity (ICANS)], serious infections, pancreatitis, tumor lysis syndrome (TLS), neutropenia/febrile neutropenia, elevated liver enzymes, leukoencephalopathy, etc.; AND
• Treatment response or stabilization of disease as indicated by CBC, bone marrow cytogenic analysis, QPCR, or FISH; AND

Acute Lymphoblastic Leukemia (Adult/Pediatric) – Relapsed or refractory disease (single agent or with a TKI)

• Patient has not exceeded 4 cycles of continued therapy or 9 total cycles of therapy

Pediatric Acute Lymphoblastic Leukemia – Relapsed or refractory disease (as a component of COG ALL1331 regimen)

• Patient has not exceeded 3 cycles of therapy

Acute Lymphoblastic Leukemia (Adult/Pediatric) – Consolidation therapy (single agent)

• Coverage may not be renewed

Acute Lymphoblastic Leukemia (Adult) – Consolidation therapy (in combination with TKI)

• Patient has not exceeded 5 cycles of therapy

Adult Acute Lymphoblastic Leukemia – Maintenance therapy

• Coverage may not be renewed

Pediatric Acute Lymphoblastic Leukemia – MRD+ or less than complete response to consolidation therapy

• Coverage may not be renewed

Pediatric Acute Lymphoblastic Leukemia – With an Interfant regimen

• Coverage may not be renewed

5. Dosage/Administration ^1,9-11,14,15

6. Billing Code/Availability Information

HCPCS Code:

• J9039 – Injection, blinatumomab, 1 microgram; 1 billable unit = 1 microgram

NDC:

• Blincyto 35 mcg single-dose powder for injection: 55513-0160-xx

7. References

1. Blincyto [package insert]. Thousand Oaks, CA; Amgen, June 2024. Accessed June 2024.
2. Referenced with permission from the NCCN Drugs & Biologics Compendium (NCCN Compendium®) blinatumomab. 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 June 2024.
3. Jen EY, Xu Q, Schetter A, Przepiorka D, et al. FDA Approval: Blinatumomab for Patients with B-cell Precursor Acute Lymphoblastic Leukemia in Morphologic Remission with Minimal Residual Disease. Clin Cancer Res. 2019 Jan 15;25(2):473-477. doi: 10.1158/1078-0432.CCR-18-2337. Epub 2018 Sep 25.
4. Kantarjian H, Stein A, Gökbuget N, et al. Blinatumomab versus Chemotherapy for Advanced Acute Lymphoblastic Leukemia. N Engl J Med. 2017 Mar 2;376(9):836-847. doi: 10.1056/NEJMoa1609783.
5. Martinelli G, Boissel N, Chevallier P, et al. Complete Hematologic and Molecular Response in Adult Patients With Relapsed/Refractory Philadelphia Chromosome-Positive B-Precursor Acute Lymphoblastic Leukemia Following Treatment With Blinatumomab: Results From a Phase II, Single-Arm, Multicenter Study. J Clin Oncol. 2017 Jun 1;35(16):1795-1802. doi: 10.1200/JCO.2016.69.3531. Epub 2017 Mar 29. Erratum in: J Clin Oncol. 2017 Aug 10;35(23):2722. J Clin Oncol. 2017 Aug 20;35(24):2856.
6. Referenced with permission from the NCCN Drugs & Biologics Compendium (NCCN Compendium®) for Pediatric Acute Lymphoblastic Leukemia 5.2024. 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 June 2024.
7. Topp MS, Gökbuget N, Stein AS, et al. Safety and activity of blinatumomab for adult patients with relapsed or refractory B-precursor acute lymphoblastic leukaemia: a multicentre, single-arm, phase 2 study. Lancet Oncol. 2015;16(1):57-66.
8. von Stackelberg A, Locatelli F, Zugmaier G, et al. Phase I/Phase II Study of Blinatumomab in Pediatric Patients With Relapsed/Refractory Acute Lymphoblastic Leukemia. J Clin Oncol. 2016;34(36):4381-4389.
9. Van Der Sluis IM, De Lorenzo P, Kotecha RS, et al. A phase 2 study to test the feasibility, safety and efficacy of the of the addition of blinatumomab to the Interfant06 backbone in infants with newly diagnosed KMT2A-rearranged acute lymphoblastic leukemia. a collaborative study of the Interfant Network. Blood 2021;138:361.
10. Advani AS, Moseley A, O'Dwyer KM, et al. SWOG 1318: A Phase II Trial of Blinatumomab Followed by POMP Maintenance in Older Patients With Newly Diagnosed Philadelphia Chromosome-Negative B-Cell Acute Lymphoblastic Leukemia. J Clin Oncol. 2022 May 10;40(14):1574-1582.
11. Hogan LE, Brown PA, Ji L, et al. Children's Oncology Group AALL1331: Phase III trial of blinatumomab in children, adolescents, and young adults with low-risk B-Cell ALL in first relapse. J Clin Oncol. 2023;41(25):4118-4129.
12. Litzow M, Sun Z, Mattison R, et al. S115: CONSOLIDATION WITH BLINATUMOMAB IMPROVES OVERALL AND RELAPSE-FREE SURVIVAL IN PATIENTS WITH NEWLY DIAGNOSED B-CELL ACUTE LYMPHOBLASTIC LEUKEMIA: IMPACT OF AGE AND MRD LEVEL IN ECOG-ACRIN E1910. Hemasphere. 2023 Aug 8;7(Suppl ):e1944062. doi: 10.1097/01.HS9.0000967372.19440.62. PMCID: PMC10428281.
13. Locatelli F, Zugmaier G, Rizzari C, et al. Effect of Blinatumomab vs Chemotherapy on Event-Free Survival Among Children With High-risk First-Relapse B-Cell Acute Lymphoblastic Leukemia: A Randomized Clinical Trial. JAMA. 2021 Mar 2;325(9):843-854. doi: 10.1001/jama.2021.0987. PMID: 33651091; PMCID: PMC7926287.
14. Foà R, Bassan R, Vitale A, et al; GIMEMA Investigators. Dasatinib-Blinatumomab for Ph-Positive Acute Lymphoblastic Leukemia in Adults. N Engl J Med. 2020 Oct 22;383(17):1613-1623. doi: 10.1056/NEJMoa2016272. PMID: 33085860.
15. Jabbour E, Short NJ, Jain N, et al. Ponatinib and blinatumomab for Philadelphia chromosome-positive acute lymphoblastic leukaemia: a US, single-centre, single-arm, phase 2 trial. Lancet Haematol. 2023 Jan;10(1):e24-e34. doi: 10.1016/S2352-3026(22)00319-2. Epub 2022 Nov 16. PMID: 36402146.

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

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