Chimeric antigen receptor T-cell (CAR-T) therapy is a cellular therapy that uses genetic engineering to alter an individual's own T-cells to produce unique receptors on their cell surface that recognize a specific protein.

CAR-T therapies are only available through their specific restricted program under a Risk Evaluation and Mitigation Strategy (REMS). Providers must enroll and comply with REMS requirements.

Brexucabtagene autoleucel (Tecartus^TM) may be considered medically necessary when the following criteria are met:

Mantle Cell Lymphoma (MCL)

• Individual 18 years of age or older; and
• Individual diagnosed with MCL; and
• Individual diagnosed with relapsed or refractory disease; and
• Disease progression following last regimen or refractory to most recent therapy [previous therapy must include a Bruton’s tyrosine kinase (BTK) inhibitor (e.g., ibrutinib, zanubrutinib, acalabrutinib) unless contraindicated]; and
• Individual has not previously received prior allogeneic hematopoietic stem cell transplant (HSCT); and
• No detectable cerebrospinal fluid malignant cells or brain metastases; and
• No history of central nervous system (CNS) lymphoma or CNS disorders; and
• Creatinine clearance (as estimated by Cockcroft Gault) greater than or equal to 60 mL/min; and
• Alanine aminotransferase (ALT) less than or equal to 2.5 times the upper limit of normal; and
• Cardiac ejection fraction (EF) greater than or equal to 50%; or

Acute Lymphoblastic Leukemia (ALL)

• Individual 18 years of age or older; and
• Individual diagnosed with B-cell precursor ALL; and
• Individual diagnosed with relapsed or refractory disease (R/R) including ANY of the following:
  • First relapse following a remission lasting less than or equal to 12 months; or
  • R/R ALL after second-line or higher therapy; or
  • R/R ALL at least 100 days after allogeneic HSCT; or
  • R/R Philadelphia chromosome-positive B-ALL following therapy that has included Tyrosine kinase inhibitors (TKIs); or
  • R/R Philadelphia chromosome-negative B-ALL; and
• Individual does not have active or serious infections; and
• Individual must not have active graft-vs-host disease; and
• Individual has not taken immunosuppressants within four (4) weeks prior to enrollment, and
• No history of central nervous system (CNS) lymphoma or CNS disorders; and
• ECOG scale of performance status less than two (2); and
• Creatinine clearance greater than or equal to 60 mL/min; and
• Alanine aminotransferase (ALT) less than or equal to 2.5 times the upper limit of normal; and
• Cardiac ejection fraction (EF) greater than or equal to 50%.

Out of specification product administration is considered experimental/investigational and, therefore, non-covered for ANY indication. There is insufficient scientific evidence to support its effectiveness and safety for ANY indication.

Additional infusions of brexucabtagene autoleucel (Tecartus) or infusion of alternative CAR-T products after an initial infusion of one product are considered experimental/investigational and therefore, non-covered. Scientific evidence does not support more than one (1) dose of a single CAR-T product per lifetime.

The use of brexucabtagene autoleucel (Tecartus) not meeting the criteria as indicated in this policy is considered not medically necessary.

Idecabtagene vicleucel (Abecma®) may be considered medically necessary when the following criteria are met:

• Individual is 18 years of age or older; and 
• Individual has relapsed or refractory multiple myeloma; and 
• Individual has received two (2) or more prior lines of therapy, including an immunomodulatory agent, a proteasome inhibitor, and an anti-CD38 monoclonal antibody; and
• Individual has adequate organ and bone marrow function; and
• Individual does not have active infections(s) or inflammatory disorders; and
• Individual has not had prior CAR-T therapy or gene therapy; and
• ECOG scale of performance status less than two (2); and
• CrCl greater than 45 mL/min; and
• Alanine aminotransferase (ALT) less than or equal to 2.5 times the upper limit of normal; and
• Cardiac ejection fraction (EF) greater than 45%

Out of specification product administration is considered experimental/investigational and, therefore, non-covered for ANY indication. There is insufficient scientific evidence to support its effectiveness and safety for ANY indication.

Additional infusions of idecabtagene vicleucel (Abecma) or infusion of alternative CAR-T products after an initial infusion of one product are considered experimental/investigational and therefore, non-covered. Scientific evidence does not support more than one (1) dose of a single CAR-T product per lifetime.

The use of idecabtagene vicleucel (Abecma) not meeting the criteria as indicated in this policy is considered not medically necessary.

Lisocabtagene maraleucel (Breyanzi®) may be considered medically necessary for the following:

• Individual is 18 years of age or older; and 
• Individual has been diagnosed with relapsed/refractory B-cell lymphoma including ANY of the following:
  • AIDS-Related B-Cell Lymphomas; or
  • Diffuse large B-cell Lymphoma (DLBCL) not otherwise specified (including DLBCL arising from indolent lymphoma); or
  • High-grade B-cell lymphoma; or
  • High-Grade B-Cell Lymphomas with Translocations of MYC and BCL2 and/or BCL6 (Double/Triple Hit Lymphoma); or
  • Post-Transplant Lymphoproliferative Disorders; or
  • Primary mediastinal large B-cell lymphoma; or
  • Refactory disease to first-line chemoimmunotherapy or relapse within 12 months of first-line chemoimmunotherapy; or
  • Refactory disease of first-line chemoiummunotherapy or relapse after first-line chemoimmunotherapy and are not eligible for hemopoietic stem cell transplantation (HSCT) due to comorbidities or age; and
• Individual has had disease progression following two or more lines of systemic therapy including anthracycline-based chemotherapy (e.g. doxorubicin, epirubicin) and an anti-CD20 antibody (e.g. rituximab); or 
• Individual has been diagnosed with relapsed/refractory chronic lymphocytic leukemia (CLL) or small lymphocytic lymphoma (SLL) and has received at least two (2) prior lines of therapy including a Bruton tyrosine kinase (BTK) inhibitor and a B-cell lymphoma 2 (BCL-2) inhibitor; and
• Individual has received or will receive a lymphodepleting chemotherapy regimen; and
• Individual has adequate organ and bone marrow function; and
• Individual does not have active infections(s) or inflammatory disorders; and
• Individual has not had prior CAR-T therapy or gene therapy; and
• ECOG scale of performance status less than or equal to two (2); and
• CrCl greater than 30 mL/min; and
• ALT less than or equal to 5 times the upper limit of normal; and
• Cardiac ejection fraction (EF) greater than or equal to 40%.

Out of specification product administration is considered experimental/investigational and, therefore, non-covered for ANY indication. There is insufficient scientific evidence to support its effectiveness and safety for ANY indication.

Additional infusions of lisocabtagene maraleucel (Breyanzi) or infusion of alternative CAR-T products after an initial infusion of one product are considered experimental/investigational and therefore, non-covered. Scientific evidence does not support more than one (1) dose of a single CAR-T product per lifetime.

The use of lisocabtagene maraleucel (Breyanzi) not meeting the criteria as indicated in this policy is considered not medically necessary.

Tisagenlecleucel (Kymriah®) may be considered medically necessary for ANY of the following indications:

Acute Lymphoblastic Leukemia (ALL)

Philadelphia Chromosome-Negative B-ALL

• Relapsed/refractory Philadelphia chromosome (Ph)-negative B-ALL; and
• Individual has refractory* or in second or later relapse** B-ALL; and
• Individual is less than 26 years of age; and
• Documentation of CD19 tumor expression in bone marrow or peripheral blood;  and
• No uncontrolled bacterial, viral or fungal infection; and
• No presence of grade 2-4 acute or extensive chronic graft-versus-host disease (GVHD); and
• No active CNS involvement by malignancy; and
• No prior anti-CD19/anti-CD3 therapy (bispecific T-cell engager, such as blinatumomab), or any other anti-CD19 therapy (such as inotuzumab ozogamicin) in the four (4) weeks preceding the apheresis collection; and 
• No prior gene therapy; and
• Karnofsky/Lansky score greater than or equal to 70; and
• Creatinine clearance (CrCl) greater than or equal to 60; and
• Alanine aminotransferase (ALT) less than or equal to five (5) times the upper limit of normal; and
• Cardiac ejection fraction (EF) greater than or equal to 45%; and
• No live vaccination within six (6) weeks prior to initiation of lymphodepleting chemotherapy; or

Philadelphia Chromosome-Positive B-ALL

• Relapsed/refractory Ph-positive B-ALL; and
• Individual is less than 26 years; and
• Individual has greater than or equal to two (2) relapses and failure of two (2) tyrosine kinase inhibitors (TKIs); and
• Documentation of CD19 tumor expression in bone marrow or peripheral blood; and
• No uncontrolled bacterial, viral or fungal infection; and
• No presence of grade 2-4 acute or extensive chronic GVHD; and
• No active CNS involvement by malignancy; and
• No prior anti-CD19/anti-CD3 therapy (bispecific T-cell engager, such as blinatumomab), or any other anti-CD19 therapy (such as inotuzumab ozogamicin) in the four (4) weeks preceding the apheresis collection; and 
• No prior gene therapy; and
• Karnofsky/Lansky score greater than or equal to 70; and
• CrCl greater than or equal to 60; and
• ALT less than or equal to five (5) times the upper limit of normal; and
• Cardiac EF greater than or equal to 45%; and
• No live vaccination within six (6) weeks prior to initiation of lymphodepleting chemotherapy; or

Acute Lymphoblastic Leukemia – Pediatric

• Ph-negative B-ALL that is minimal residual disease positive (MRD+) after consolidation therapy; or
• Ph-like B-ALL that is MRD+ after consolidation therapy; or
• Refractory Ph-positive B-ALL; or
• Ph-positive B-ALL with less than complete response, MRD+ at end of consolidation, or high-risk genetics; or  
• Ph-positive B-ALL with relapse post-HSCT; and
  • Individual is less than 26 years; and
  • Documentation of CD19 tumor expression in bone marrow or peripheral blood; and
  • No uncontrolled bacterial, viral or fungal infection; and
  • No presence of grade 2-4 acute or extensive chronic GVHD; and
  • No active CNS malignancy; and
  • No prior anti-CD19/anti-CD3 therapy (bispecific T-cell engager, such as blinatumomab), or any other anti-CD19 therapy (such as inotuzumab ozogamicin) in the four (4) weeks preceding the apheresis collection; and
  • No prior gene therapy; and
  • Karnofsky/Lansky score greater than or equal to 70; and
  • ECOG performance status less than two (2); and
  • CrCl greater than or equal to 60; and
  • ALT less than or equal to five (5) times the upper limit of normal; and
  • Cardiac EF greater than or equal to 45%; and
  • No live vaccination within six (6) weeks prior to initiation of lymphodepleting chemotherapy; or

B-Cell Lymphomas

• Treatment of individuals 18 years of age or older with ANY of the following large B-cell lymphomas:
  • Relapsed or refractory diffuse large B-cell lymphoma (DLBCL), not otherwise specified (NOS); or
  • Relapsed or refractory DLBCL arising from follicular lymphoma; or
  • Relapsed or refractory High grade B-cell lymphoma; and
    • Greater than or equal to two (2) lines of chemotherapy, including rituximab and anthracycline; or 
    • Relapsed following autologous  HSCT; and
    • When ALL of the following criteria are met:
      • Documentation of CD19 tumor expression demonstration in bone marrow or peripheral blood; and
      • No active cns malignancy; and
      • No prior allogeneic HSCT; and
      • ECOG performance status less than two (2); and
      • No uncontrolled bacterial, viral or fungal infection; and
      • Creatinine clearance greater than or equal to 60; and
      • ALT less than or equal to five (5) times the upper limit of normal; and
      • Cardiac ejection fraction greater than or equal to 45%; and
      • Absolute lymphocyte count greater than or equal to 300/μL; and
      • No prior gene therapy; and
      • No live vaccination within six (6) weeks prior to initiation of lymphodepleting chemotherapy; or
• Treatment of individuals 18 years of age or older with ANY of the following B-cell lymphomas:
  • Relapsed AIDS-related diffuse large B-cell lymphoma; or
  • Primary effusion lymphoma; or
  • HHV8-positive diffuse large B-cell lymphoma, not otherwise specific (NOS); or
  • Diffuse large B-cell lymphoma; or
  • Primary mediastinal large B-cell lymphoma; or
  • High-grade B-cell lymphomas with translocations of MYC and BCL2 and/or BCL6 (double/triple hit lymphoma); or
  • High-grade B-cell lymphomas, not otherwise specified; and
  • When used as ONE of the following:
    • Additional therapy for individuals with intention to proceed to transplant who have partial response following second-line therapy for relapsed or refractory disease; or
    • Treatment of disease in second relapse or greater in individuals with partial response, no response, or progressive disease following therapy for relapsed or refractory disease (if anti-CD19 CAR T-cell therapy not previously given); and
    • When ALL of the following criteria are met:
      • Documentation of CD19 tumor expression demonstration in bone marrow or peripheral blood; and
      • No active CNS malignancy; and
      • ECOG performance status less than two (2); and
      • No uncontrolled bacterial, viral or fungal infection; and
      • No prior anti-CD19/anti-CD3 therapy or any other anti-CD19 therapy in the four (4) weeks preceding the apheresis collection; and
      • No prior gene therapy; and
      • Karnofsky/Lansky score greater than or equal to 70; and
      • CrCl greater than or equal to 60; and
      • ALT less than or equal to five (5) times the upper limit of normal; and
      • Cardiac EF greater than or equal to 45%; and
      • Absolute lymphocyte count greater than or equal to 300/μL; and
      • No live vaccination within six (6) weeks prior to initiation of lymphodepleting chemotherapy; or

Follicular Lymphoma (grade 1-2), Histologic Transformation of Nodal Marginal Zone Lymphoma to Diffuse Large B-Cell Lymphoma, or Post-Transplant Lymphoproliferative Disorders (PTLD)

• Histologic transformation to diffuse large B-cell lymphoma (DLBCL) in individuals who have received minimal or no chemotherapy prior to histologic transformation to DLBCL and have partial response, no response, or progressive disease after treatment with greater than or equal to 2 chemoimmunotherapy regimens which included at least one anthracycline or anthracenedione-based regimen, unless contraindicated; or
• Histologic transformation to DLBCL in individuals who have received multiple lines of prior therapies (not including anti-CD19 CAR T-cell therapy) for indolent or transformed disease (only after treatment with greater than or equal to 2 chemoimmunotherapy regimens which included at least one anthracycline or anthracenedione-based regimen, unless contraindicated); or
• Therapy for indolent or transformed histologic transformation of nodal marginal zone lymphoma to DLBCL (if anti-CD19 CAR T-cell therapy was not previously given) for individual who has received multiple lines of prior therapies including greater than or equal to 2 chemoimmunotherapy regimens (should have received at least one anthracycline or anthracenedione-based regimen, unless contraindicated); or
• Treatment for relapsed or refractory monomorphic PTLD (B-cell type) as additional therapy for individuals with intention to proceed to transplant who have partial response following second-line chemoimmunotherapy; or
• Treatment of monomorphic PTLD (B-cell type) in second relapse or greater (if anti-CD19 CAR T-cell therapy not previously given); and
• When ALL of the following criteria are met:
  • Documentation of CD19 tumor expression demonstration in bone marrow or peripheral blood; and
  • No active CNS malignancy; and
  • ECOG performance status less than two (2); and
  • No uncontrolled bacterial, viral or fungal infection; and
  • No prior anti-CD19/anti-CD3 therapy or any other anti-CD19 therapy in the four (4) weeks preceding the apheresis collection; and
  • No prior gene therapy; and
  • Karnofsky/Lansky score greater than or equal to 70; and
  • CrCl greater than or equal to 60; and
  • ALT less than or equal to five (5) times the upper limit of normal; and
  • Cardiac EF greater than or equal to 45%; and
  • Absolute lymphocyte count greater than or equal to 300/μL; and
  • No live vaccination within six (6) weeks prior to initiation of lymphodepleting chemotherapy.

Adult Relapsed or Refractory (r/r) Follicular Lymphoma

• Refractory or relapsed (within six (6) months) Follicular Lymphoma (Grade 1, 2, 3A); or
• Third-line and subsequent therapy (if not previously given) for partial response, no response, relapsed, or progressive disease in patients with indications for treatment (after two (2) or more prior chemoimmunotherapy regimens); and
  • No active or serious infections; and
  • No transformed lymphoma, or other aggressive lymphomas; and
  • No prior allogeneic HSCT; and  
  • No active CNS malignancy.

Out of specification product administration is considered experimental/investigational and, therefore, non-covered for ANY indication. There is insufficient scientific evidence to support its effectiveness and safety for ANY indication.

Additional infusions of tisagenlecleucel (Kymriah) or infusion of alternative CAR-T products after an initial infusion of one product are considered experimental/investigational and therefore, non-covered. Scientific evidence does not support more than one (1) dose of a single CAR-T product per lifetime.

Refractory is defined by not achieving an initial complete remission after two (2) cycles of a standard chemotherapy regimen (primary refractory). Subjects who were refractory to subsequent chemotherapy regimens after an initial remission are considered chemorefractory.

**Relapse is defined by greater than 5% lymphoblasts and second or subsequent bone marrow (BM) relapse, or any BM relapse after allogeneic (stem cell transplant) SCT and must be greater than or equal to six (6) months from SCT at the time of tisagenlecleucel infusion.

The use of tisagenlecleucel (Kymriah) not meeting the criteria as indicated in this policy is considered not medically necessary.

Axicabtagene ciloleucel (Yescarta®) may be considered medically necessary for individuals 18 years of age or older for ANY of the following indications:

B-Cell Lymphomas

• Relapsed and/or refractory diffuse large B-cell lymphoma (DLBCL), not otherwise specified; or
• Relapsed and/or refractory high-grade B-cell lymphoma; or
• Relapsed and/or refractory primary mediastinal large B-cell lymphoma (PMBCL); or
• Relapsed and/or refractory DLBCL arising from follicular lymphoma; or
  • Individual has received two (2) or more lines of systemic therapy; and
  • No active CNS involvement by malignancy; and
  • No prior anti-CD19/anti-CD3 therapy (bispecific T-cell engager, such as blinatumumab), or any other anti-CD19 therapy (such as inotuzumab ozogamycin) in the four (4) weeks preceding the apheresis collection; and 
  • No prior cellular gene therapy; and
  • ECOG scale of performance status less than or equal to one (1); and
  • No live vaccination within six (6) weeks prior to initiation of lymphodepleting chemotherapy; and
• Lymphocyte depletion with intravenous cyclophosphamide and intravenous fludarabine has been given in the previous five (5) days; or
• Large B-cell lymphoma that is refractory to first-line chemoimmunotherapy; or
• Large B-cell lymphoma that relapses within 12 months after completion of first-line chemoimmunotherapy; and
  • Individual had not yet received treatment for relapsed or refractory lymphoma; and
  • Individual does not have primary mediastinal B-cell lymphoma; and
  • No history of CNS malignancy; and
  • No active infections; and
  • Individual does not need urgent therapy due to tumor mass effect; and
  • ECOG scale of performance status less than or equal to one (1); and
  • Cardiac ejection fraction greater than or equal to 50%; and
  • Creatinine clearance greater than or equal to 60 mL/min.

AIDS-Related B-Cell Lymphomas, Diffuse Large B-Cell Lymphoma, or High-Grade B-Cell Lymphomas

• Relapsed AIDS-related diffuse large B-cell lymphoma; or
• Primary effusion lymphoma; or
• HHV8-positive diffuse large B-cell lymphoma, not otherwise specific (NOS); or
• Diffuse large B-cell lymphoma; or
• Primary mediastinal large B-cell lymphoma; or
• High-grade B-cell lymphomas with translocations of MYC and BCL2 and/or BCL6 (double/triple hit lymphoma); or
• High-grade B-cell lymphomas, not otherwise specified; and
• When used as ANY of the following:
  • Additional therapy for individuals with intention to proceed to transplant who have partial response following second-line therapy for relapsed or refractory disease; or
  • Treatment (if anti-CD19 CAR T-cell therapy was not previously given) of disease in second relapse or greater in individuals with partial response, no response, or progressive disease following therapy for relapsed or refractory disease; and
  • When ALL of the following criteria are met:
    • No active CNS involvement by malignancy; and
    • No prior anti-CD19/anti-CD3 therapy (bispecific T-cell engager, such as blinatumumab), or any other anti-CD19 therapy (such as inotuzumab ozogamycin) in the four (4) weeks preceding the apheresis collection; and 
    • No prior cellular gene therapy; and
    • ECOG scale of performance status less than or equal to one (1); and
    • No live vaccination within six (6) weeks prior to initiation of lymphodepleting chemotherapy; or
    • Lymphocyte depletion with intravenous cyclophosphamide and intravenous fludarabine has been given in the previous five (5) days; or

Follicular Lymphoma (grade 1-2), Histologic Transformation of Nodal Marginal Zone Lymphoma to Diffuse Large B-Cell Lymphoma, or Post-Transplant Lymphoproliferative Disorders (PTLD)

• Treatment of relapsed or refractory follicular lymphoma (FL) after two (2) or more lines of systemic therapy; or
• Third-line and subsequent therapy for relapsed/refractory or progressive FL in individuals with indications for treatment after two (2) prior therapies; or
• Histologic transformation to DLBCL in individuals who have received minimal or no chemotherapy prior to histologic transformation to DLBCL and have partial response, no response, or progressive disease after treatment with greater than or equal to 2 chemoimmunotherapy regimens which included at least one anthracycline or anthracenedione-based regimen, unless contraindicated; or
• Histologic transformation to DLBCL in individuals who have received multiple lines of prior therapies (not including anti-CD19 CAR T-cell therapy) for indolent or transformed disease (only after treatment with greater than or equal to 2 chemoimmunotherapy regimens which included at least one anthracycline or anthracenedione-based regimen, unless contraindicated); or
• Therapy for indolent or transformed histologic transformation of nodal marginal zone lymphoma to DLBCL (if anti-CD19 CAR T-cell therapy was not previously given) for individual who has received multiple lines of prior therapies including greater than or equal to 2 chemoimmunotherapy regimens (should have received at least one anthracycline or anthracenedione-based regimen, unless contraindicated); or
• Treatment for relapsed or refractory monomorphic PTLD (B-cell type) as additional therapy for individuals with intention to proceed to transplant who have partial response following second-line chemoimmunotherapy; or
• Treatment of monomorphic PTLD (B-cell type) in second relapse or greater (if anti-CD19 CAR T-cell therapy not previously given); and
• When ALL of the following criteria are met:
  • No active CNS involvement by malignancy; and
  • No prior anti-CD19/anti-CD3 therapy (bispecific T-cell engager, such as blinatumumab), or any other anti-CD19 therapy (such as inotuzumab ozogamycin) in the four (4) weeks preceding the apheresis collection; and 
  • No prior cellular gene therapy; and
  • ECOG scale of performance status less than or equal to one (1); and
  • No live vaccination within six (6) weeks prior to initiation of lymphodepleting chemotherapy; and
  • Lymphocyte depletion with intravenous cyclophosphamide and intravenous fludarabine has been given in the previous five (5) days

Limitation of Use: Axicabtagene ciloleucel (Yescarta) is not indicated for the treatment of patients with primary CNS lymphoma.

Out of specification product administration is considered experimental/investigational and, therefore, non-covered for ANY indication. There is insufficient scientific evidence to support its effectiveness and safety for ANY indication.

Additional infusions of axicabtagene ciloleucel (Yescarta) or infusion of alternative CAR-T products after an initial infusion of one product are considered experimental/investigational and therefore, non-covered. Scientific evidence does not support more than one (1) dose of a single CAR-T product per lifetime.

The use of axicabtagene ciloleucel (Yescarta) not meeting the criteria as indicated in this policy is considered not medically necessary.

Ciltacabtagene autoleucel (Carvykti™) may be considered medically necessary when ALL of the following criteria are met:

• Individuals 18 years of age or older; and
• Individual has Relapsed or lenalidomide refractory multiple myeloma; and
• Individual has received at least one (1) prior line of therapy including a proteasome inhibitor, an immunomodulatory agent, and
• No prior treatment with CAR-T therapy directed at any target; and
• No prior therapy targeted to B-cell maturation antigen (BCMA); and
• No known active or history of CNS disease (i.e seizure or cerebrovascular ischemia); and
• Does not require chronic immunosuppression; and
• ECOG scale of performance status less than two (2); and
• CrClgreater than or equal to 40 mL/min; and
• Cardiac ejection fraction greater than or equal to 45%.
  

Out of specification product administration is considered experimental/investigational and, therefore, non-covered for ANY indication. There is insufficient scientific evidence to support its effectiveness and safety for ANY indication.

Additional infusions of ciltacabtagene autoleucel (Carvykti) or infusion of alternative CAR-T products after an initial infusion of one product are considered experimental/investigational and therefore, non-covered. Scientific evidence does not support more than one (1) dose of a single CAR-T product per lifetime.

The use of ciltacabtagene autoleucel (Carvykti) not meeting the criteria as indicated in this policy is considered not medically necessary.

NOTE: In addition to the above criteria, product specific dosage and/or frequency limits may apply in accordance with the U.S. Food and Drug Administration (FDA)-approved product prescribing information, national compendia, Centers for Medicare and Medicaid Services (CMS) and other peer reviewed resources or evidence-based guidelines. Highmark may deny, in full or in part, reimbursement for utilization that does not fall within the applicable dosage and/or frequency limits.