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

Delaware Mandate:

Effective September 1, 2017, 18 Delaware Code §§3338B and 3555B, require that no individual policy or contract of health insurance, or certificate issued thereunder, which is delivered, issued for delivery, renewed, modified, altered, or amended in this State by any health insurer, health service corporation or health maintenance organization that directly or indirectly covers the treatment of cancer shall limit or exclude coverage for a drug approved by the United States Food and Drug Administration by mandating that the insured shall first be required to fail to successfully respond to a different drug or drugs or prove a history of failure of such drug or drugs; provided, however that the use of such drug or drugs is consistent with best practices for the treatment of stage 4 advanced, metastatic cancer or, in the case of other cancers, the use of the drug is supported by national clinical guidelines, national standards of care, or peer reviewed medical literature for the treatment of the cancer, or in the case of targeted therapy, the target at issue.

Tisagenlecleucel (Kymriah®) may be considered medically necessary for the treatment of refractory* or second or later relapsed** B-cell precursor acute lymphoblastic leukemia (ALL) in individuals up to and including 25 years of age when all of the following criteria are met:

• Documentation of CD19 tumor expression demonstration 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 central nervous system 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 gene therapy; and
• Karnofsky/Lansky score greater than or equal to 70; and
• No live vaccination within six (6) weeks prior to initiation of lymphodepleting chemotherapy; and
• Apheresis product received and accepted by manufacturing site.

Tisagenlecleucel (Kymriah) may be considered medically necessary for the treatment of Philadelphia chromosome-positive ALL in individuals up to and including 25 years of age when all of the following criteria are met:

• Failed two (2) lines of tyrosine kinase inhibitor (TKI); and
• Documentation of CD19 tumor expression demonstration 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 central nervous system 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 gene therapy; and
• Karnofsky/Lansky score greater than or equal to 70; and
• No live vaccination within six (6) weeks prior to initiation of lymphodepleting chemotherapy; and 
• Apheresis product received and accepted by manufacturing site.

Tisagenlecleucel (Kymriah) may be considered medically necessary for the treatment of adult individuals with relapsed or refractory (r/r) large B-cell lymphoma after two or more lines of systemic therapy including diffuse large B-cell lymphoma (DLBCL) not otherwise specified, high grade B-cell lymphoma and DLBCL arising from follicular lymphoma; when all of the following criteria are met:

• Greater than or equal to 18 years of age; and
• Greater than or equal to two (2) lines of chemotherapy, including rituximab and anthracycline, or relapsed following autologous hematopoietic stem cell transplantation (HSCT); and
• No active central nervous system 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
• Alanine aminotransferase 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; and 
• Apheresis product received and accepted by manufacturing site.

Tisagenlecleucel (Kymriah) is considered experimental/investigational and therefore non-covered for any other indications than those listed above. There is insufficient evidence regarding its effectiveness and safety for any other indications.

* 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.

Because of the risk of cytokine release syndrome (CRS) and neurological toxicities, Kymriah is available only through a restricted program under a Risk Evaluation and Mitigation Strategy (REMS) called the KYMRIAH REMS. The required components of the KYMRIAH REMS are: 

• Healthcare facilities that dispense and administer Kymriah must be enrolled and comply with the REMS requirements. Certified healthcare facilities must have on-site, immediate access to tocilizumab, and ensure that a minimum of two doses of tocilizumab are available for each patient for administration within two hours after Kymriah infusion, if needed for treatment of CRS.
• Certified healthcare facilities must ensure that healthcare providers who prescribe, dispense or administer tisagenlecleucel (Kymriah) are trained about the management of CRS and neurological toxicity.

Axicabtagene ciloleucel (Yescarta®) may be considered medically necessary for individuals 18 years of age or older when ALL the following criteria are met:

• Individual has a diagnosis of ANY ONE of the following aggressive forms of NHL:
  • Relapsed and/or refractory diffuse large B-cell lymphoma (DLBCL), not otherwise specified after two (2) or more lines of therapy; or
  • Relapsed and/or refractory high-grade B-cell lymphoma after two (2) or more lines of therapy; or
  • Relapsed and/or refractory double hit lymphoma after two (2) or more lines of therapy; or
  • Relapsed and/or refractory triple hit lymphoma after two (2) or more lines of therapy; or
  • Relapsed and/or refractory primary mediastinal large B-cell lymphoma (PMBCL); or
  • Transformed follicular lymphoma (t-FL) failing to achieve complete remission with one line of chemoimmunotherapy incorporating anthracycline or anthracenedione, at a minimum; or
  • Monomorphic post-transplant B-lymphoproliferative disorder (B-PTLD) which has progressed after reduction or withdrawal of immunosuppression and has failed to achieve complete remission with salvage chemoimmunotherapy or relapses after achieving complete remission; and
• No active central nervous system 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; and
• Apheresis product received and accepted by manufacturing site.

Axicabtagene ciloleucel (Yescarta) is considered experimental/investigational and therefore non-covered for any other indication than those listed above. There is insufficient evidence regarding its effectiveness and safety for any other indications.

Because of the risk of CRS and neurological toxicities, axicabtagene ciloleucel (Yescarta) is available only through a restricted program under a REMS called the YESCARTA REMS. The required components of the YESCARTA REMS are:

• Healthcare facilities that dispense and administer axicabtagene ciloleucel (Yescarta) must be enrolled and comply with the REMS requirements. Certified healthcare facilities must have on-site, immediate access to tocilizumab, and ensure that a minimum of two doses of tocilizumab are available for each individual for administration within two hours after axicabtagene ciloleucel (Yescarta) infusion, if needed for treatment of CRS.
• Certified healthcare facilities must ensure that healthcare providers who prescribe, dispense or administer Axicabtagene ciloleucel (Yescarta) are trained about the management of CRS and neurological toxicities. 

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.