(Intravenous)

Last Review Date: 08/05/2025

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, 08/2025

1. Length of Authorization ^1,9-11,17-20
   • Relapsed or refractory disease (single agent or with a TKI) (Adult/Pediatric):
     • Initial: Prior authorization validity will be provided initially for 30 weeks for a total of five cycles (2 cycles of induction followed by 3 cycles of consolidation)
     • Renewal: Prior authorization validity may be renewed 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) (Pediatric):
     • Initial: Prior authorization validity will be provided initially for a maximum of 24 weeks (three 56-day cycles)
     • Renewal: Prior authorization validity may NOT be renewed
   • Frontline induction therapy (in combination with TKI) (Adult):

• Initial: Prior authorization validity will be provided initially for 4 weeks
• Renewal: Prior authorization validity may NOT be renewed
  • Consolidation therapy (Adult/Pediatric):
    • Initial: Prior authorization validity will be provided initially for 30 weeks (five 42-day cycles)
    • Renewal: Prior authorization validity may NOT be renewed
  • MRD+ (Adult/Pediatric):

• • • Initial: Prior authorization validity will be provided initially for 24 weeks for a total of four cycles (1 cycle of induction followed by 3 cycles of consolidation)
    • Renewal: Prior authorization validity may NOT be renewed
  • Maintenance therapy (alternating with POMP) (Adult):
    • Initial: Prior authorization validity will be provided initially for 24 weeks (one 42-day cycle)
    • Renewal: Prior authorization validity may be renewed every 24 weeks for a maximum of 4 additional authorizations (four 42-day cycles)
  • Infant ALL in combination with an Interfant regimen:
    • Initial: Prior authorization validity will be provided initially for 28 days
    • Renewal: Prior authorization validity may NOT be renewed

2. Dosing Limits

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

• • Acute Lymphoblastic Leukemia (ALL) (Adult/Pediatric)
• 980 billable units per 42 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 ^1,2,16

• • 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 frontline induction therapy; AND
  • Used in combination with a tyrosine kinase inhibitor (TKI)§ for Philadelphia chromosome-positive (Ph+) disease; OR
• Used as part of consolidation therapy; AND
  • Used for Philadelphia chromosome-negative (Ph-) disease; OR
  • Used for Ph+ disease; AND
    • Used as a single agent as a component of inotuzumab ozogamicin + mini-hyperCVD regimen if refractory to TKIs; OR
    • Used in combination with a TKI§; OR
• Used as maintenance therapy; AND
  • Used as a single agent alternating with POMP (prednisone, vincristine, methotrexate, and mercaptopurine); AND
    • Patient has Ph+ disease; AND

–    Patient is refractory to TKIs; OR

• • • Patient has Ph- disease; OR
• Patient has relapsed or refractory 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. Refer to NCCN guidelines for TKI/mutation contraindications.

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

• Patient is at least 1 month of age*; AND
  • Patient has infant ALL; AND
    • Used in combination with an interfant regimen (e.g., Interfant-06, Interfant-99, etc.) as consolidation therapy; OR
  • Patient has B-cell precursor ALL; AND
    • Used for MRD+ ALL as a single agent for first or second complete remission with MRD greater than or equal to 0.1% †; OR
    • Used as part of consolidation therapy; AND
      • Used for Ph+ (BCR::ABL1-positive) disease in combination with a TKI^ (with or without chemotherapy); OR
      • Used for Ph- (BCR::ABL1-negative) disease; OR

• • • • Used for Ph-like (BCR::ABL1-like) disease; AND
        • Used as a single agent; OR
        • Used in combination with chemotherapy (Note: may also be used with a TKI^ or ruxolitinib); OR
    • Used for relapsed or refractory disease; AND
      • Used as a single agent †; AND
        • Used for Ph- (BCR::ABL1-negative) disease; OR
        • Used for Ph+ (BCR::ABL1-positive) disease intolerant/refractory to TKI; OR
      • Used as a component of COG AALL1331 regimen; AND
        • Used as a single agent for Ph- (BCR::ABL1-negative) disease; OR
        • Used in combination with a TKI^ for Ph+ (BCR::ABL1-positive) disease

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

^TKI options include dasatinib or imatinib. Refer to NCCN guidelines for regimens.

† 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:

4. • 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
   • Duration of authorization has not been exceeded (refer to Section I); 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
5. Dosage/Administration ^{1,9-11,14,15,17-20}

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 Inc.; April 2025. Accessed July 2025.
2. Referenced with permission from the NCCN Drugs & Biologics Compendium (NCCN Compendium®) blinatumomab. National Comprehensive Cancer Network, 2025. 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 2025.
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 3.2025. National Comprehensive Cancer Network, 2025. 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 2025.

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, Elia L, et al. Long-term results of the dasatinib-blinatumomab protocol for adults Philadelphia-positive ALL. J Clin Oncol. 2024;42:881-885.
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.

16. Referenced with permission from the NCCN Drugs & Biologics Compendium (NCCN Compendium®) for Acute Lymphoblastic Leukemia 2.2025. 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 2025.
17. Wu X, Lu S, Zhang X, et al. The combination of a tyrosine kinase inhibitor and blinatumomab in patients with Philadelphia chromosome-positive acute lymphoblastic leukemia or Philadelphia chromosome-like acute lymphoblastic leukemia. Cancer Med. 2024 Sep; 13(17):e70161. doi: 10.1002/cam4.70161. PMID: 39240182; PMCID: PMC11378354.
18. Gupta S, Rau R, Kairalla J, et al. Blinatumomab in Standard-Risk B-Cell Acute Lymphoblastic Leukemia in Children. N Engl J Med. 2025 Feb 27;392(9):875-891. doi: 10.1056/NEJMoa2411680. Epub 2024 Dec 7.
19. Litzow M, Sun Z, Mattison R, et al. Blinatumomab for MRD-Negative Acute Lymphoblastic Leukemia in Adults. N Engl J Med. 2024;391:320-333.
20. Jabbour E, Short NJ, Jain N, et al. Hyper-CVAD and sequential blinatumomab for newly diagnosed Philadelphia chromosome-negative B-cell acute lymphocytic leukaemia: a single- arm, single-centre, phase 2 trial. Lancet Haematol 2022;9:e878-e885.
21. Jabbour E, Short NJ, Senapati J, et al. Mini-hyper-CVD plus inotuzumab ozogamicin, with or without blinatumomab, in the subgroup of older patients with newly diagnosed Philadelphia chromosome-negative B-cell acute lymphocytic leukaemia: long-term results of an open-label phase 2 trial. Lancet Haematol 2023;10:e433-e444.

Appendix 1 – Covered Diagnosis Codes