Medicare Advantage

Medical Policy

Notification

Blinatumomab (Blincyto®)

Notification Issued Date:

This AmeriHealth New Jersey Medicare Advantage policy will become effective 01/01/2024.

Title:

Blinatumomab (Blincyto®)

Policy #:

MA08.058h

Policy

The Company reserves the right to reimburse only those services that are furnished in the most appropriate and cost-effective setting that is appropriate to the member’s medical needs and condition.

This policy uses coverage criteria primarily based on applicable Medicare statutes, regulations, NCDs, LCDs, CMS manuals and other applicable Medicare coverage documents. In the absence of fully established coverage criteria from these Medicare coverage documents for a specific medical service or item, the criterion/indication/service indicated by an asterisk below (*) is based on internal coverage criteria developed by the Company in consideration of peer-reviewed medical literature, clinical practice guidelines, regulatory status, and/or expert opinion.

INDEX OF MEDICALLY NECESSARY INDICATIONS

This policy addresses numerous medically necessary indications:

PHILADELPHIA CHROMOSOME-POSITIVE B-ALL IN ADULT INDIVIDUALS and/or ADOLESCENT AND YOUNG ADULTS (AYA), WHEN SPECIFIED
PHILADELPHIA CHROMOSOME-NEGATIVE B-ALL IN ADULT INDIVIDUALS
PHILADELPHIA CHROMOSOME-NEGATIVE B-ALL IN ADULT INDIVIDUALS and/or ADOLESCENT AND YOUNG ADULTS (AYA), WHEN SPECIFIED
ACUTE LYMPHOBLASTIC LEUKEMIA (ALL) IN INFANTS
ACUTE LYMPHOBLASTIC LEUKEMIA (ALL) IN PEDIATRIC INDIVIDUALS

MEDICALLY NECESSARY

Blinatumomab (Blincyto) is considered medically necessary and, therefore, covered for individuals with acute lymphoblastic leukemia (ALL) who meet any of the following criteria, including Dosing and Frequency Requirements:

* National Comprehensive Cancer Network (NCCN). NCCN Drugs & Biologics Compendium. Blinatumomab. [NCCN Web site]. 2025.

PHILADELPHIA CHROMOSOME-POSITIVE B-ALL IN ADULT INDIVIDUALS and/or ADOLESCENT AND YOUNG ADULTS (AYA), WHEN SPECIFIED

Relapsed/refractory (R/R) therapy as a single agent (CD19 antigen directed) in individuals of all ages. * US Food and Drug Administration (FDA) 04/2025.

Therapy in combination with a TKI^† during one of the following regimens:

Frontline induction therapy (Adolescent and Young Adult [AYA] without substantial comorbidities and adults)
Frontline consolidation therapy (AYA without substantial comorbidities and adults). (NOTE: Blinatumomab + TKI is a National Comprehensive Cancer Network [NCCN]--preferred regimen in consolidation regardless of MRD status for those who have not previously received blinatumomab)
Relapsed/refractory (R/R) therapy for adults

PHILADELPHIA CHROMOSOME-NEGATIVE B-ALL IN ADULT INDIVIDUALS

BCR::ABL1-negative B-cell precursor ALL with minimal residual disease (MRD)-negative remission (less than 0.01% leukemic cells in bone marrow as assessed on flow cytometry) * Merative^TM Micromedex® DRUGDEX® (electronic version).

Frontline therapy as a single agent, as part of one of the following regimens**:

sequentially as part of consolidation with inotuzumab ozogamicin + mini-hyperCVD§
alternating with POMP§ as part of maintenance if induced with inotuzumab ozogamicin + mini-hyperCVD§ + sequential blinatumomab

If refractory to TKIs, as part of one of the following regimens**:

sequentially as part of consolidation with inotuzumab ozogamicin + mini-hyperCVD§
alternating with POMP§ as part of maintenance if induced with inotuzumab ozogamicin + mini-hyperCVD§ + sequential blinatumomab

Relapsed/refractory (R/R) therapy, as component of one of the following regimens**:

sequentially as part of consolidation with inotuzumab ozogamicin + mini-hyperCVD§
alternating with POMP§ as part of maintenance if induced with inotuzumab ozogamicin + mini-hyperCVD§ + sequential blinatumomab

PHILADELPHIA CHROMOSOME-NEGATIVE B-ALL IN ADULT INDIVIDUALS and/or ADOLESCENT AND YOUNG ADULTS (AYA), WHEN SPECIFIED

CD19-positive B-cell precursor acute lymphoblastic leukemia (B-ALL) in first or second complete remission with MRD+ disease (greater than or equal to 0.1%) in individuals of all ages. * US Food and Drug Administration (FDA) 04/2025.

Consolidation therapy for AYA without substantial comorbidities and adults for one of the following regimens**:

single agent if multiagent therapy is contraindicated
single agent (NCCN-preferred) incorporated with continued multiagent therapy if not already included in a multi-part regimen

Consolidation therapy as a single agent alternating with ECOG1910§ for CD20-positive disease for one of the following regimens:

Frontline therapy (AYA without substantial comorbidities and adults)
Refractory therapy in adults aged ≥65 years or adults with substantial comorbidities
In late relapse (>3 years from initial diagnosis) if regimen used in frontline for AYA without substantial comorbidities and adults

Sequential consolidation therapy for AYA and adults aged <65 years without substantial comorbidities as a single agent, as a component of HyperCVAD§ for one of the following regimens:

Frontline therapy
In late relapse (>3 years from initial diagnosis) if regimen used in frontline

Maintenance therapy for AYA and adults aged <65 years without substantial comorbidities, as a component of POMP§ alternating with blinatumomab, in individuals who were induced with HyperCVAD§ + sequential blinatumomab as part of consolidation therapy

Relapsed/refractory (R/R) Therapy as a CD19 antigen directed single agent with or without multiagent therapy (NCCN-preferred) in individuals of all ages. * US Food and Drug Administration (FDA) 04/2025.

ACUTE LYMPHOBLASTIC LEUKEMIA (ALL) IN INFANTS

CD19-positive B-cell precursor acute lymphoblastic leukemia (B-ALL) in first or second complete remission with MRD+ disease (greater than or equal to 0.1%). * US Food and Drug Administration (FDA) 04/2025.
Consolidation therapy in combination with risk-stratified interfant regimens for infant ALL with KMT2A status (11q23) rearranged and not rearranged

ACUTE LYMPHOBLASTIC LEUKEMIA (ALL) IN PEDIATRIC INDIVIDUALS

CD19-positive B-cell precursor acute lymphoblastic leukemia (B-ALL) in first or second complete remission with MRD+ disease (greater than or equal to 0.1%). * US Food and Drug Administration (FDA) 04/2025.
Consolidation therapy in combination with any of the following for BCR::ABL1-negative B-ALL:

Standard risk-average or Standard risk-high blinatumomab arm of COG1731 regimen
COG AALL1131 regimen
DFCI ALL Protocol 16-001 regimen, based on DFCI ALL Protocol 11-001 regimen
Total Therapy XVII regimen, based on Total Therapy XVI regimen

Consolidation therapy in combination with any of the following for BCR::ABL1-like B-ALL:

COG AALL1131 regimen + dasatinib
COG AALL1521 regimen ± ruxolitinib
DFCI-ALL Protocol 16-001 regimen (VHR arm) + dasatinib for ABL class kinase fusion
Total Therapy XVII regimen + dasatinib for ABL class kinase fusion
Total Therapy XVII regimen ± ruxolitinib for mutations associated with JAK-STAT pathway activation

Consolidation therapy in combination with any of the following for BCR::ABL1-positive B-ALL:

Standard arm of COG AALL1631 (based on COG AALL1122/EsPhALL regimen) with EsPhALL backbone + imatinib or dasatinib
COG AALL0622 regimen + dasatinib
Total Therapy XVII regimen + dasatinib

Single-agent therapy for any of the following conditions:

Relapsed/refractory (R/R) therapy:

Philadelphia Chromosome-Positive B-ALL (CD19 antigen directed). * US Food and Drug Administration (FDA) 04/2025.
Ph-negative CD19-negative B-ALL. * US Food and Drug Administration (FDA) 04/2025.
BCR::ABL1-negative B-ALL
BCR::ABL1-positive TKI intolerant/refractory B-ALL

Standard or High Risk Disease‡

Less than complete response or Minimal residual disease Positive (MRD+)

Standard-risk or high risk BCR::ABL1-negative or BCR::ABL1-like B-ALL that is MRD+ after induction in combination with intensified consolidation chemotherapy
Standard-risk or high-risk BCR::ABL1-negative or BCR::ABL1-like B-ALL that was MRD+ after induction who remain MRD+ after intensified consolidation therapy
High risk BCR::ABL1-positive B-ALL with less than complete response or MRD+ at end of consolidation incorporated into frontline consolidation therapy with imatinib or dasatinib
High risk BCR::ABL1-positive B-ALL with less than complete response or MRD+ at end of consolidation with imatinib or dasatinib

Minimal residual disease Low or Negative (MRD-)

Standard-risk or high-risk BCR::ABL1-negative or BCR::ABL1-like B-ALL that is MRD- after induction, in combination with risk-stratified consolidation therapy
Standard risk BCR::ABL1-positive B-ALL with low MRD incorporated into frontline consolidation therapy with imatinib or dasatinib

Relapsed/refractory (R/R) therapy as a component of COG AALL1331 regimen for one of the following conditions:

BCR::ABL1-negative B-ALL
BCR::ABL1-positive B-ALL, in combination with dasatinib or imatinib

^†TKI options include bosutinib, dasatinib, imatinib, nilotinib, or ponatinib. Imatinib use in first line should be restricted to those who cannot tolerate broader acting TKIs. TKI/mutation contraindications: Bosutinib - T315I, V299L, G250E, or F317L; Dasatinib - T315I/A, F317L/V/I/C or V299L; Imatinib too numerous to include; Nilotinib - T315I, Y253H, E255K/V, F359V/C/I or G250E.

** There are data to support the benefit of rituximab for CD20-positive disease in addition to frontline multiagent therapy for AYA and adults aged less than 65 years without substantial comorbidities (especially if aged <60 years).

‡ Risk Stratification of ALL:

Standard risk criteria: Aged ≥1 y to <10 y and white blood cell (WBC) count <50,000/mm3
High-risk criteria: Aged <1 y or ≥10 y, and/or WBC count ≥50,000/mm3

§ Abbreviations for Regimens:

ECOG1910: cyclophosphamide, cytarabine, daunorubicin, dexamethasone, etoposide, mercaptopurine, high-dose methotrexate, leucovorin, pegaspargase, vincristine, rituximab for CD20-positive disease
HyperCVAD: hyperfractionated cyclophosphamide, mesna, vincristine, doxorubicin, dexamethasone, IT methotrexate, IT cytarabine alternating with high-dose methotrexate, leucovorin, dose-adjusted cytarabine, IT methotrexate, IT cytarabine, (and with rituximab if CD20-positive disease)
mini-hyperCVD (hyperfractionated cyclophosphamide, vincristine, dexamethasone, inotuzumab ozogamicin alternating with cytarabine, methotrexate, inotuzumab ozogamicin)
POMP (mercaptopurine, vincristine, methotrexate, prednisone)

DOSING AND FREQUENCY REQUIREMENTS

* US Food and Drug Administration (FDA) 04/2025.

The Company reserves the right to modify the Dosing and Frequency Requirements listed in this policy to ensure consistency with the most recently published recommendations for the use of blinatumomab (Blincyto). Changes to these guidelines are based on a consensus of information obtained from resources such as, but not limited to, the US Food and Drug Administration (FDA); Company-recognized authoritative pharmacology compendia; or published peer-reviewed clinical research. The professional provider must supply supporting documentation (i.e., published peer-reviewed literature) in order to request coverage for an amount of blinatumomab (Blincyto) outside of the Dosing and Frequency Requirements listed in this policy. For a list of Company-recognized pharmacology compendia, view our policy on off-label coverage for prescription drugs and biologics.

Accurate member information is necessary for the Company to approve the requested dose and frequency of this drug. If the member’s dose, frequency, or regimen changes (based on factors such as changes in member weight or incomplete therapeutic response), the provider must submit those changes to the Company for a new approval based on those changes as part of the precertification process. The Company reserves the right to conduct postpayment review and audit procedures for any claims submitted for blinatumomab (Blincyto).

Ph-POSITIVE OR Ph-NEGATIVE B-CELL ACUTE LYMPHOBLASTIC LEUKEMIA (B-ALL)
For Ph-positive or Ph-Negative B-ALL, a treatment course consists of one cycle of blinatumomab (Blincyto) for induction (Cycle 1), followed by up to three additional cycles for consolidation treatment (Cycles 2–4). Each cycle consists of 4 weeks of continuous intravenous infusion followed by a 2-week treatment-free interval (total, 42 days). Do not exceed a maximum of 875 mcg, or 25 vials, per month.

Induction Cycle 1 and Consolidation Cycles 2–4

Days 1–28
- Weight ≥45 kg: 28 mcg/day
- Weight <45 kg: 15 mcg/m2/day, not to exceed 28 mcg/day
Days 29–42: 14-day treatment-free interval

RELAPSED OR REFRACTORY B-CELL ALL
For relapsed or refractory B-ALL, a treatment course consists of up to two cycles of blinatumomab (Blincyto) for induction (Cycles 1–2), followed by three additional cycles for consolidation treatment (Cycles 3–5) and up to four additional cycles of continued therapy (Cycles 6–9). Each induction or consolidation therapy cycle consists of 4 weeks of continuous intravenous infusion followed by a 2-week treatment-free interval (total, 42 days). Each continued therapy cycle consists of 4 weeks of continuous intravenous infusion followed by an 8-week treatment-free interval (total, 84 days). Do not exceed a maximum of 875 mcg, or 25 vials, per month.

Induction Cycle 1

Days 1–7

Weight ≥45 kg: 9 mcg/day
Weight <45 kg: 5 mcg/m2/day, not to exceed 9 mcg/day

Induction Cycle 1

Days 8–28

Weight ≥45 kg: 28 mcg/day
Weight <45 kg: 15 mcg/m2/day, not to exceed 28 mcg/day

Induction Cycle 1

Days 29–42: 14-day treatment-free interval

Induction Cycle 2 and

Consolidation Cycles 3–5

Days 1–28
- Weight ≥45 kg: 28 mcg/day
- Weight <45 kg: 15 mcg/m2/day, not to exceed 28 mcg/day
Days 29–42: 14-day treatment-free interval

Consolidation Cycles 6–9

Days 1–28
- Weight ≥45 kg: 28 mcg/day
- Weight <45 kg: 15 mcg/m2/day, not to exceed 28 mcg/day
Days 29–84: 56-day treatment-free interval

NOT MEDICALLY NECESSARY

Utilization of more than 875 units of service (UOS) equivalent to 25 vials of blinatumomab (Blincyto) per month is considered not medically necessary and, therefore, not covered.

One UOS equals one microgram, and, thus, one vial equals 35 UOS.
Reconstituted blinatumomab (Blincyto) must be prepared using the combination of vials that result in the least amount of wastage for the dosage amount being administered.
- Per the manufacturer's 2-day infusion protocol, five vials (or 175 UOS) should be used to reconstitute 6 days of drug.
- Per the manufacturer's 7-day infusion protocol, six vials (or 210 UOS) should be used to reconstitute 7 days of drug.

EXPERIMENTAL/INVESTIGATIONAL

All other uses of blinatumomab (Blincyto) are considered experimental/investigational and, therefore, not covered unless the indication is supported as an accepted off-label use, as defined in the medical policy on off-label coverage for prescription drugs and biologics.

REQUIRED DOCUMENTATION

The individual's medical record must reflect the medical necessity for the drug. These medical records may include, but are not limited to: records from the professional provider's office, hospital, nursing home, home health agencies, therapies, and test reports.

The company may conduct reviews and audits of services to our members, regardless of the participation status of the provider. All documentation is to be available to the Company upon request. Failure to produce the requested information may result in a denial of the drug.

When coverage of blinatumomab (Blincyto) is requested outside of the Dosing and Frequency Requirements listed in this policy, the prescribing professional provider must supply documentation (i.e., published peer-reviewed literature) to the Company that supports this request.

Guidelines

This policy is consistent with Medicare’s coverage determination for blinatumomab (Blincyto). The Company’s payment methodology may differ from Medicare.

BENEFIT APPLICATION

Subject to the applicable Evidence of Coverage, blinatumomab (Blincyto) is covered under the medical benefits of the Company’s Medicare Advantage products when the medical necessity criteria and Dosing and Frequency Requirements listed in this medical policy are met.

Certain drugs are available only through the member's medical benefit (Part B benefit), depending on how the drug is prescribed, dispensed, or administered. For Medicare Advantage members, blinatumomab (Blincyto) is covered ONLY under a member's medical benefit (Part B benefit).

NATIONAL COMPREHENSIVE CANCER NETWORK (NCCN) AGE DEFINITION

NCCN considers adolescent and young adult (AYA) to be within the age range of 15–39 years.

US FOOD AND DRUG ADMINISTRATION (FDA) STATUS

Blinatumomab (Blincyto) was approved by the FDA on December 3, 2014, for the treatment of Philadelphia chromosome–negative relapsed or refractory B-cell precursor acute lymphoblastic leukemia (B-ALL). Supplemental approvals for blinatumomab (Blincyto) have since been issued by the FDA.

The safety and effectiveness of blinatumomab (Blincyto) have been established in the pediatric population aged one month and older.

INPATIENT ADMISSION

When the medical necessity criteria has been met, the inpatient admission for administration of blinatumomab (Blincyto), as recommended by the FDA, is covered in accordance with the following time-frames*:

First Cycle: Days 1–3 of therapy (Ph-positive or Ph-Negative B-ALL) or Days 1–9 of therapy (relapsed or refractory B-ALL)
Second Cycle: Days 1–2 of therapy

*Consideration will be given for individuals receiving therapy in subsequent cycle starts and for reinitiation of therapy (e.g., if treatment is interrupted for ≥4 hours). Inpatient hospital stays that are longer than the preceding timeframes must be re-evaluated for medical necessity. Home infusion therapy is an option for subsequent therapy.

Description

ACUTE LYMPHOBLASTIC LEUKEMIA (ALL)

The American Cancer Society estimates that, in the year 2025, there will be approximately 6100 individuals in the United States newly diagnosed with ALL (i.e., acute lymphocytic leukemia). About 40% of all cases will be in adults; the majority of cases occur in children. The 5-year overall survival rate for ALL in children is higher than 90%, but is only 40% to 60% in adults (although these rates vary depending on the subtype of ALL and other prognostic factors).

The goal of therapy is to achieve complete remission, obtain an undetectable minimal residual disease (MRD) result, and to then undergo a hematopoietic stem cell transplant (HSCT). About 70% to 90% of adults will achieve complete remission from ALL after induction therapy; however, approximately half of these individuals will experience relapse due to chemoresistant disease. One indicator of clinical relapse is the MRD result: the lower the MRD measurement, the better the chance of overall survival. It has been reported that up to 80% of individuals who fail to clear MRD experience a clinical relapse despite continued chemotherapy. The role of MRD testing is less understood in adults compared with children due to paucity of data in adults. There is no standard definition of MRD. According to National Comprehensive Cancer Network (NCCN) Guidelines for ALL, MRD-positive disease was defined as 0.01% or greater bone marrow mononuclear cells (MNCs); MRD-negative disease was MNCs less than 0.01%.

Treatment of ALL is dependent on the particular subtype of the disease. Although most adults are Philadelphia chromosome (PH)–negative, approximately 20% to 30% of adults with ALL have a genetic mutation referred to as Ph–positive. Ph-positive ALL accounts for less than 5% of children with ALL, but the incidence is higher in adolescents. Treatment of ALL subtypes may consist of chemotherapy (induction, consolidation, and maintenance), tyrosine kinase inhibitors (TKIs) (e.g., dasatinib [Sprycel], imatinib [Gleevec], ponatinib [Iclusig]), and monoclonal antibodies (e.g., blinatumomab [Blincyto]).

BLINATUMOMAB (BLINCYTO)

A T cell (immune cell) is activated when its receptors bind to the antigens on a cancer cell. The T cell releases cytotoxic components that form pores in the tumor cell's structure and causes cell death. However, cancer cells have found many ways to evade T-cell recognition (e.g., mutation, blocking T-cell signaling). Blinatumomab (Blincyto), a monoclonal antibody, was created to combat this evasion. Blinatumomab (Blincyto) is the first bispecific CD19-directed CD3 T-cell engager (BiTE) immunotherapy product to be approved by the US Food and Drug Administration (FDA). It creates a bridge between the T cell and the cancer cell, by binding to two different proteins at the same time (CD19 located on malignant B cells and CD3 located on T cells); this triggers the activation of the T cells, which ultimately will cause the death of the malignant cells.

Blinatumomab (Blincyto) obtained accelerated approval by the FDA on December 3, 2014, for the treatment of Ph-negative relapsed or refractory B-cell precursor acute lymphoblastic leukemia (B-ALL). Subsequent approvals were established for those with Ph-positive relapsed or refractory B-ALL and in those with B-ALL in first or second complete remission with MRD.

CYTOKINE RELEASE SYNDROME
Cytokines are proteins that communicate with cells about the need for immune assistance. Cytokines are secreted by both healthy and cancerous cells. When blinatumomab (Blincyto) infusion is initiated, a transient release (increase) of cytokines occurs in response to the T-cell activation, called cytokine-release syndrome (CRS). CRS is common during the initial infusions of monoclonal antibodies and typically subsides with subsequent doses. Symptoms may range from mild in severity to life-threatening or fatal reactions, and include flu-like reactions, hypotension, tachycardia, gastrointestinal disturbances, dyspnea, shock, disseminated intravascular coagulation (DIC), capillary leak syndrome (CLS), and hemophagocytic lymphohistiocytosis/macrophage activation syndrome (HLH/MAS). For relapsed or refractory B-cell ALL, it has been reported that the highest risk of CRS occurs during the first 9 days of the first cycle and during the first 2 days of the second cycle of blinatumomab (Blincyto). For MRD-positive B-cell ALL, it has been reported that the highest risk of CRS occurs during the first 3 days of the first cycle and during the first 2 days of the second cycle of blinatumomab (Blincyto). For these reasons, hospitalization is recommended during these days of therapy. Also, per FDA labeling, "For all subsequent cycle starts and reinitiation (e.g., if treatment is interrupted for 4 or more hours), supervision by a healthcare professional or hospitalization is recommended."

PEER-REVIEWED LITERATURE

SUMMARY
The safety and efficacy of blinatumomab (Blincyto) was evaluated in an open-label, multicenter, single-arm, Phase II study of 185 adults with Ph-negative relapsed or refractory B-ALL. Blinatumomab (Blincyto) was administered as a continuous intravenous (IV) infusion. In the first cycle, the initial dose was 9 mcg/day for week 1, then 28 mcg/day for the remaining 3 weeks. In the second and subsequent cycles, 28 mcg/day was administered starting on day 1 of each cycle. The median number of treatment cycles administered was two (range, one to five). A reported 77 of 185 (41.6%) individuals achieved complete remission or complete remission with partial hematologic recovery (CR/CRh) within the first two treatment cycles, which was the primary endpoint of the study; the majority of responses (81%, 62 of 77 individuals) occurred within the first cycle of treatment. Among those who achieved CR/CRh, 39% (30 of 77 individuals) proceeded to HSCT. There was also a 75% (58 of 77 individuals) achievement of MRD response. The study also reported that 32% of individuals in the study experienced complete remission for approximately 6.7 months after at least 4 weeks of infusion treatment.

A Phase III, randomized, open-label, multicenter, confirmatory study demonstrating an increase in overall survival was performed by Kantarjian et al. in 2017. Adult participants (N=405) with relapsed or refractory B-ALL were randomly assigned 2:1 to receive blinatumomab (Blincyto) or standard of care chemotherapy. The median number of blinatumomab (Blincyto) cycles received was two (range, one to nine cycles). The median overall survival was statistically significantly longer in the blinatumomab (Blincyto) group (7.7 months) compared with the chemotherapy group (4 months).

Martinelli et al. in 2017 performed an open label, Phase II study of adults with Ph-positive relapsed or refractory B-ALL who had prior treatment with at least one second-generation or later TKI or were intolerant to second-generation or later TKIs and intolerant or refractory to imatinib. The primary endpoint of CR or CRh during the first two cycles of blinatumomab (Blincyto) was obtained by 16 of 45 participants (36%). Additionally, 88% of those who obtained CRh achieved a complete MRD response. The median relapse-free survival and overall survival were 6.7 and 7.1 months, respectively.

The safety and effectiveness of blinatumomab (Blincyto) was studied in the pediatric population (N=70) with relapsed or refractory B-ALL in an open-label, multicenter, single arm trial. The median number of blinatumomab (Blincyto) cycles received was one (range, one to five cycles). Twenty-three of 70 (32.9%) participants achieved CR or CR/CRh within the first two treatment cycles with 17 of 23 (73.9%) occurring within Cycle 1 of treatment.

Gökbuget et al. in 2018 performed an open-label, multicenter, single-arm study of 86 adults with B-ALL who had received at least three chemotherapy blocks of standard ALL therapy, were in first or second hematologic complete remission (CR1 and CR2), and had MRD at a level of 0.1% or greater. Blinatumomab (Blincyto) 15 mcg/m²/day up to a maximum dosage of 28 mcg/day IV was administered for up to four cycles. The primary endpoint was complete MRD response status after one cycle of blinatumomab. Results showed that 73.8% of individuals in CR1 and 50% of individuals in CR2 obtained complete MRD response. The median hematological relapse-free survival was 35.2 months in individuals in CR1 and 12.3 months in individuals in CR2.

OFF-LABEL INDICATIONS

There may be additional indications contained in the Policy section of this document due to evaluation of criteria highlighted in the Company’s off-label policy, and/or review of clinical guidelines issued by leading professional organizations and government entities.

References

American Cancer Society. Key Statistics for ALL. 01/16/2025. Available at: Key Statistics for Acute Lymphocytic Leukemia (ALL) | American Cancer Society. Accessed July 18, 2025.

American Cancer Society. Leukemia in children. Available at: https://www.cancer.org/cancer/leukemia-in-children.html. Accessed July 18, 2025.

American Cancer Society. Survival Rates for Childhood Leukemias. 02/12/2019. Available at: Childhood Leukemia Survival Rates | American Cancer Society. Accessed July 18, 2025.

American Hospital Formulary Service (AHFS). Drug Information 2025. Blinatumomab. [Lexicomp Online Web site]. 05/10/2025. Available at: http://online.lexi.com/lco/action/home [via subscription only]. Accessed July 11, 2025.

Blinatumomab (Blincyto) Prescribing Information. Thousand Oaks, CA: Amgen Inc.; 04/2025. Available at: http://www.blincyto.com/. Accessed June 27, 2025.

Breslin S. Cytokine-release syndrome: overview and nursing implications. Clin J Oncol Nurs. 2007;11(1 Suppl):37-42.

Elsevier’s Clinical Pharmacology Compendium. Blinatumomab. [ClinicalKey Web site]. 06/17/2025. Available at: https://www.clinicalkey.com/pharmacology/ [via subscription only]. Accessed July 11, 2025.

Gökbuget N, Dombret H, Bonifacio M, et al. Blinatumomab for minimal residual disease in adults with B-cell precursor acute lymphoblastic leukemia. Blood. 2018;131(14):1522-1531.

Horton TM, McNeer JL. Treatment of acute lymphoblastic leukemia/lymphoma in children and adolescents. [UpToDate Web Site]. 04/09/2025. Available at: http://www.uptodate.com/contents/overview-of-the-treatment-of-acute-lymphoblastic-leukemia-in-children-and-adolescents?source=search_result&search=blincyto&selectedTitle=9~9. Accessed July 18, 2025.

Kantarjian H, Stein A, Gökbuget N, et al. Blinatumomab versus chemotherapy for advanced acute lymphoblastic leukemia. N Engl J Med. 2017;376(9):836-847.

Larson RA. Treatment of relapsed or refractory acute lymphoblastic leukemia in adults. [UpToDate Web Site]. 03/03/2025. Available at: http://www.uptodate.com/contents/treatment-of-relapsed-or-refractory-acute-lymphoblastic-leukemia-in-adults?source=search_result&search=blincyto&selectedTitle=4~9. Accessed July 18, 2025.

Lexi-Drugs Compendium. Blinatumomab. 06/10/2025. [Lexicomp Online Web site]. Available at: http://online.lexi.com/lco/action/home [via subscription only]. Accessed July 11, 2025.

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;35(16):1795-1802.

MerativeTM Micromedex® DRUGDEX® (electronic version). Merative, Ann Arbor, Michigan, USA. Blinatumomab (Blincyto). [Micromedex® Web site]. Updated 05/15/2025. Available at: http://www.micromedexsolutions.com/micromedex2/librarian [via subscription only]. Accessed July 11, 2025.

National Comprehensive Cancer Network (NCCN). NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines). ALL. Version 1.2025. 05/15/2025. [NCCN Website]. Available at: http://www.nccn.org/professionals/physician_gls/pdf/all.pdf [via free subscription]. Accessed June 24, 2025.

National Comprehensive Cancer Network (NCCN). NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines). Pediatric Acute Lymphoblastic Leukemia. Version 3. 2025. 03/17/2025. [NCCN Website]. Available at: https://www.nccn.org/professionals/physician_gls/pdf/ped_all.pdf [via free subscription]. Accessed June 24, 2025.

National Comprehensive Cancer Network (NCCN). NCCN Guidelines for Patients: ALL in Children. 2025. [NCCN Website]. Available at: NCCN Guidelines for Patients: Acute Lymphoblastic Leukemia in Children . Accessed July 8, 2025.

National Comprehensive Cancer Network (NCCN). NCCN Drugs & Biologics Compendium. Blinatumomab. [NCCN Web site]. 2025. Available at: http://www.nccn.org/professionals/drug_compendium/content/contents.asp [via subscription only]. Accessed June 24, 2025.

Noridian Medicare Local Coverage Determination. Local Coverage Article for External Infusion Pumps - Policy Article (A52507). Original 10/01/15. Updated 02/19/2025. Available at: https://www.cms.gov/medicare-coverage-database/view/article.aspx?articleId=52507. Accessed July 8, 2025.

Noridian Medicare Local Coverage Determination. Local Coverage Determination (LCD): External Infusion Pumps (L33794). Original: 10/01/2015. Updated 10/01/2024. Available at: https://www.cms.gov/medicare-coverage-database/view/lcd.aspx?LCDId=33794. Accessed July 8, 2025.

Seiter K. Acute lymphoblastic leukemia. Updated 11/18/2024. Available at: http://emedicine.medscape.com/article/207631-overview#showall. Accessed June 27, 2025.

Stock W, Estrov Z. Clinical use of minimal residual disease detection in acute lymphoblastic leukemia. [UpToDate Web Site]. 06/10/2024. Available at: http://www.uptodate.com/contents/clinical-use-of-minimal-residual-disease-detection-in-acute-lymphoblastic-leukemia?source=search_result&search=acute+lymphoblastic+leukemia+adult&selectedTitle=7~150. Accessed July 18, 2025.

Stock W, Estrov Z. Detection of measurable residual disease in acute lymphoblastic leukemia/lymphoblastic lymphoma. [UpToDate Web Site]. 10/01/2024. Available at: https://www.uptodate.com/contents/detection-of-measurable-residual-disease-in-acute-lymphoblastic-leukemia?search=measurable residual disease&source=search_result&selectedTitle=1~150&usage_type=default&display_rank=1. Accessed July 18, 2025.

Topp MS, Goekbuget N, Stein AS, et al. Confirmatory open-label, single-arm, multicenter phase 2 study of the BiTE antibody blinatumomab in patients (pts) with relapsed/refractory B-precursor acute lymphoblastic leukemia (r/r ALL). 2014 ASCO Annual Meeting - Abstract Number: 7005. J Clin Oncol 2014;32:5s (suppl; abstr 7005).

Topp MS, Gökbuget N, Zugmaier G, et al. Long-term follow-up of hematologic relapse-free survival in a phase 2 study of blinatumomab in patients with MRD in B-lineage ALL. Blood. 2012;120(26):5185-5187.

Topp MS, Kufer P, Gökbuget N, et al. Targeted therapy with the T-cell-engaging antibody blinatumomab of chemotherapy-refractory minimal residual disease in B-lineage acute lymphoblastic leukemia patients results in high response rate and prolonged leukemia-free survival. J Clin Oncol. 2011;29(18):2493-2498.

US Food and Drug Administration (FDA). Center for Drug Evaluation and Research. Drugs @FDA. Blinatumomab (Blincyto) approval letter and prescribing information. [FDA Web site]. 04/2025. Available at:
https://www.accessdata.fda.gov/scripts/cder/daf/. Accessed June 24, 2025.

Coding

CPT Procedure Code Number(s)

N/A

ICD - 10 Procedure Code Number(s)

N/A

ICD - 10 Diagnosis Code Number(s)

Report the most appropriate diagnosis code in support of medically necessary criteria as listed in the policy.

HCPCS Level II Code Number(s)

J9039

Injection, blinatumomab, 1 mcg

Revenue Code Number(s)

N/A

MPMiscCodesNarrativesPub

Coding and Billing Requirements

Cross Reference

Policy History

Revisions From MA08.058h:

10/20/2025

This version of the policy will become effective 10/20/2025.

This policy was updated to communicate the updated medical necessity criteria for acute lymphoblastic leukemia (ALL), in alignment with National Comprehensive Cancer Network (NCCN) recommendations. Extensive updates were done to add regimens for ALL with additional mutations, and also a change in initially categorizing ALL regimens by Philadelphia Chromosome status, then secondarily by minimal residual disease (MRD) status.

The Guidelines Section clarifies that NCCN considers adolescent and young adult (AYA) to be within the age range of 15–39 years.

All of the ICD-10 CM codes have been removed from this policy, since they are informational. Report the most appropriate diagnosis code in support of medically necessary criteria as listed in the policy.

Revisions From MA08.058g:

11/04/2024

This version of the policy will become effective 11/04/2024.

This policy was updated to communicate additional medical necessity criteria for acute lymphoblastic leukemia (ALL), in alignment with National Comprehensive Cancer Network (NCCN) recommendations.

Revisions From MA08.058f:

01/01/2024	Effective 01/01/2024 this policy applies to New Jersey Medicare Advantage (MA) lines of business.
02/27/2023	This version of the policy will become effective 02/27/2023. This policy was updated to communicate the additional Medical Necessity criteria for Acute lymphoblastic leukemia (ALL) in infants, in alignment with National Comprehensive Cancer Network (NCCN) recommendations. "RISK EVALUATION AND MITIGATION STRATEGY (REMS)" strategy information was removed from the policy since the FDA released Blincyto of its REMS strategy requirement on 12/05/2022, due to its benefits outweighing any risks.

01/01/2024

Effective 01/01/2024 this policy applies to New Jersey Medicare Advantage (MA) lines of business.

02/27/2023

This version of the policy will become effective 02/27/2023.

This policy was updated to communicate the additional Medical Necessity criteria for Acute lymphoblastic leukemia (ALL) in infants, in alignment with National Comprehensive Cancer Network (NCCN) recommendations.

"RISK EVALUATION AND MITIGATION STRATEGY (REMS)" strategy information was removed from the policy since the FDA released Blincyto of its REMS strategy requirement on 12/05/2022, due to its benefits outweighing any risks.

Revisions From MA08.058e:

06/20/2022

This version of the policy will become effective 06/20/2022.

This policy was updated to communicate the changes in the Medical Necessity criteria for Acute lymphoblastic leukemia (ALL) in adults and pediatric individuals with minimal residual disease (MRD+), MRD-, MRD unavailable, or persistent/rising MRD, or relapsed/refractory disease, in alignment with National Comprehensive Cancer Network (NCCN) recommendations.

Revisions From MA08.058d:

06/07/2021

This version of the policy will become effective 06/07/2021.

The policy has undergone a routine review, and the medical necessity criteria have been revised to reflect:

The updated US Food and Drug Administration (FDA) terminology by including "CD-19-positive" and "precursor" into the following:

CD19-positive B-cell precursor acute lymphoblastic leukemia (ALL)

The updated National Comprehensive Cancer Network (NCCN) criteria for:

Ph-negative or Ph-like B-ALL in pediatric individuals who are MRD+ after consolidation therapy
Ph-positive B-ALL in pediatric individuals with less than complete response or MRD+ at end of consolidation

The following ICD-10 CM code has been added to this policy:
C91.01 Acute lymphoblastic leukemia, in remission

Revisions From MA08.058c:

12/02/2020	This policy has been reissued in accordance with the Company's annual review process.
05/22/2019	This policy has been reissued in accordance with the Company's annual review process.
10/08/2018	This version of the policy will become effective 10/08/2018. This policy has been updated in consideration of revisions within the US Food and Drug Administration (FDA) labeling, National Comprehensive Cancer Network (NCCN) compendia, and Noridian Medicare for blinatumomab (Blincyto®). Dosing and Frequency Requirements have been added for all indications. A position of Not Medically Necessary has been added for doses above 875 units of service (UOS) or 25 vials of blinatumomab (Blincyto®) per month, per Noridian Medicare.

12/02/2020

This policy has been reissued in accordance with the Company's annual review process.

05/22/2019

This policy has been reissued in accordance with the Company's annual review process.

10/08/2018

This version of the policy will become effective 10/08/2018.

This policy has been updated in consideration of revisions within the US Food and Drug Administration (FDA) labeling, National Comprehensive Cancer Network (NCCN) compendia, and Noridian Medicare for blinatumomab (Blincyto®).

Dosing and Frequency Requirements have been added for all indications.

A position of Not Medically Necessary has been added for doses above 875 units of service (UOS) or 25 vials of blinatumomab (Blincyto®) per month, per Noridian Medicare.

Revisions From MA08.058b:

12/27/2017

The policy has undergone a routine review, and the medical necessity criteria have been revised to reflect the updated US Food and Drug Administration (FDA) and National Comprehensive Cancer Network (NCCN) criteria.

Revisions From MA08.058a:

12/21/2016	The policy has been reviewed and reissued to communicate the Company’s continuing position on blinatumomab (Blincyto).
01/01/2016	This policy has been identified for the HCPCS code update, effective 01/01/2016. The following HCPCS code has been added to this policy, as Medically Necessary: J9039 Injection, blinatumomab, 1 microgram The following HCPCS code has been termed from this policy: C9449 Injection, blinatumomab, 1 mcg The following HCPCS codes have been deleted from this policy: J3590, J7799

Revisions From MA08.058:

07/03/2015

This new policy was developed to communicate the Company’s coverage criteria for blinatumomab (Blincyto™).

Version Effective Date:

10/20/2025

Version Issued Date:

10/20/2025

Version Reissued Date: