Chimeric Antigen Receptor Therapy for Hematologic Malignancies

Section: Therapy
Effective Date: June 01, 2020
Revised Date: May 11, 2020
Revision Effective Date: June 01, 2020
Last Reviewed: May 19, 2020

Description

The spontaneous regression of certain cancers (e.g., renal cell carcinoma, melanoma) supports the idea that a individual’s immune system can delay tumor progression and, on rare occasions, can eliminate tumors altogether. These observations have led to research into various immunotherapies designed to stimulate a individual’s own immune system. Chimeric antigen receptor T-cell therapy is a specific form of adoptive immunotherapy that involves harvesting cells from a individual or donor, a manufacturing process during which cells are genetically modified with engineered CAR protein to permit targeted activation and therapy, and infusion of cells into the individual.

Criteria

Chimeric antigen receptor T-cell (CAR-T) therapy with tisagenlecleucel intravenous infusion is considered medically necessary for relapseda or refractoryb individuals with B-cell acute lymphoblastic leukemia if they meet all of the following criteria:

  • Confirmed diagnosis of CD19-positive B-cell acute lymphoblastic leukemia with morphologic bone marrow tumor involvement (≥5% lymphoblasts)
  • Are up to 25 years old at the time of infusion
  • Have not received prior treatment with tisagenlecleucel or any other gene therapy or are being considered for treatment with any other gene therapy
  • Have adequate organ function with no significant deterioration in organ function expected within 4 weeks after apheresis
  • Do not have any of the following:
    • Burkitt lymphoma
    • Active hepatitis B, C, or any uncontrolled infection
    • Grade 2 to 4 graft-versus-host disease
    • Concomitant genetic syndrome with the exception of Down syndrome
    • Received allogeneic cellular therapy, such as donor lymphocyte infusion, within 6 weeks prior to tisagenlecleucel infusion
    • Individual has active central nervous system 3 acute lymphoblastic leukemia (i.e., white blood cell count ≥5 cells/μL in cerebrospinal fluid with presence of lymphoblasts)

a Relapsed disease describes the reappearance of leukemia cells in the bone marrow or peripheral blood after the attainment of a complete remission with chemotherapy and/or allogeneic cell transplant

b Refractory (resistant) disease is defined as those individuals who fail to obtain complete response with induction therapy, ie, failure to eradicate all detectable leukemia cells (<5% blasts) from the bone marrow and blood with subsequent restoration of normal hematopoiesis (>25% marrow cellularity and normal peripheral blood counts)

 

CAR-T therapy with tisagenlecleucel intravenous (except as indicateda) infusion is considered medically necessary for relapsed or refractoryb individuals with aggressive types of non-Hodgkin lymphoma if they meet all of the following criteria:

  • Are adults (age ≥18) at the time of infusion
  • Histologically confirmed diagnosis of diffuse large B-cell lymphoma, not otherwise specified; or primary mediastinal large B-cell lymphomaa or high-grade B-cell lymphoma or diffuse large B-cell lymphoma arising from follicular lymphoma
  • Received adequate prior therapy including all of the following
    • Anti-CD20 monoclonal antibody for CD20-positive tumor
    • Anthracycline-containing chemotherapy regimen

For subjects with transformed follicular lymphoma, prior chemotherapy for follicular lymphoma and subsequently have chemorefractory disease after transformation to diffuse large B-cell lymphoma:

  • Have adequate organ and bone marrow function as determined by the treating oncologist/hematologist
  • Have not received prior CD19-directed CAR T-cell therapy treatment or any other gene therapy or are being considered for treatment with any other gene therapy

AND

  • do not have primary central nervous system lymphoma

aTisagenlecleucel intravenous infusion is consideredinvestigationalfor the treatment of relapsed or refractory primary mediastinal large B-cell lymphoma

b Relapsed or refractory disease is defined as progression after 2 or more lines of systemic therapy (which may or may not include therapy supported by autologous cell transplant)

 

CAR-T therapy with axicabtagene ciloleucel infusion is considered medically necessary for relapsed or refractorya individuals with aggressive types of non-Hodgkin lymphoma if they meet all of the following criteria:

  • Are adults (age ≥18) at the time of infusion
  • Histologically confirmed diagnosis of diffuse large B-cell lymphoma, not otherwise specified; or primary mediastinal large B-cell lymphomaor high-grade B-cell lymphoma or diffuse large B-cell lymphoma arising from follicular lymphoma
  • Received adequate prior therapy including all of the following
    • Anti-CD20 monoclonal antibody for CD20-positive tumor
    • Anthracycline-containing chemotherapy regimen

For subjects with transformed follicular lymphoma, prior chemotherapy for follicular lymphoma and subsequently have chemorefractory disease after transformation to diffuse large B-cell lymphoma:

  • Have adequate organ and bone marrow function as determined by the treating oncologist/hematologist
  • Have not received prior CD19-directed CAR T-cell therapy treatment or any other gene therapy or are being considered for treatment with any other gene therapy

AND

  • do not have primary central nervous system lymphoma

a Relapsed or refractory disease is defined as progression after 2 or more lines of systemic therapy (which may or may not include therapy supported by autologous cell transplant)

Policy Guidelines

Central nervous system (CNS) disease for B-cell acute lymphoblastic leukemia is defined by the following groups:

  • CNS 1: Absence of blasts on cerebrospinal fluid cytospin preparation, regardless of the white blood cell (WBC) count
  • CNS 2: WBC count of less than 5/mL and blasts on cytospin findings
  • CNS 3: WBC count of 5/mL or more and blasts on cytospin findings and/or clinical signs of CNS leukemia (e.g., facial nerve palsy, brain/eye involvement, hypothalamic syndrome)

Tisagenlecleucel and axicabtagene ciloleucel have black box warnings because of the risks of cytokine release syndrome (CRS) and neurologic toxicities (NT) that include fatal or life-threatening reactions. They should not be administered to individuals with active infection or inflammatory disorders. It is recommended that severe or life-threatening CRS be treated with tocilizumab. Individuals should be monitored for neurologic events after treatment.

Tisagenlecleucel (Kymriah) and axicabtagene ciloleucel (Yescarta) are available only through a restricted program under a risk evaluation and mitigation strategy (REMS) called the Kymriah REMS and Yescarta REMS, respectively. The requirement for the REMS components are as follows:

  • Health care facilities that dispense and administer tisagenlecleucel or axicabtagene ciloleucel must be enrolled and comply with the REMS requirements.
  • Certified health care facilities must have onsite, immediate access to tocilizumab, and ensure that a minimum of 2 doses of tocilizumab are available for each individual for administration within 2 hours after tisagenlecleucel or axicabtagene ciloleucel infusion, if needed for treatment of cytokine release syndrome.
  • Certified health care facilities must ensure that health care providers who prescribe, dispense, or administer tisagenlecleucel or axicabtagene ciloleucel are trained to manage cytokine release syndrome and neurologic toxicities.

CAR-T therapy is considered investigational for all other applications

Procedure Codes

0537T 0538T 0539T 0540T Q2041 Q2042

Diagnosis Codes

C82.00 C82.01 C82.02 C82.03 C82.04 C82.05 C82.06
C82.07 C82.08 C82.09 C82.10 C82.11 C82.12 C82.13
C82.14 C82.15 C82.16 C82.17 C82.18 C82.19 C82.20
C82.21 C82.22 C82.23 C82.24 C82.25 C82.26 C82.27
C82.28 C82.29 C82.30 C82.31 C82.32 C82.33 C82.34
C82.35 C82.36 C82.37 C82.38 C82.39 C82.40 C82.41
C82.42 C82.43 C82.44 C82.45 C82.46 C82.47 C82.48
C82.49 C82.50 C82.51 C82.52 C82.53 C82.54 C82.55
C82.56 C82.57 C82.58 C82.59 C82.60 C82.61 C82.62
C82.63 C82.64 C82.65 C82.66 C82.67 C82.68 C82.69
C82.80 C82.81 C82.82 C82.83 C82.84 C82.85 C82.86
C82.87 C82.88 C82.89 C82.90 C82.91 C82.92 C82.93
C82.94 C82.95 C82.96 C82.97 C82.98 C82.99 C83.00
C83.01 C83.02 C83.03 C83.04 C83.05 C83.06 C83.07
C83.08 C83.09 C83.10 C83.11 C83.12 C83.13 C83.14
C83.15 C83.16 C83.17 C83.18 C83.19 C83.30 C83.31
C83.32 C83.33 C83.34 C83.35 C83.36 C83.37 C83.38
C83.39 C83.50 C83.51 C83.52 C83.53 C83.54 C83.55
C83.56 C83.57 C83.58 C83.59 C83.70 C83.71 C83.72
C83.73 C83.74 C83.75 C83.76 C83.77 C83.78 C83.79
C83.80 C83.81 C83.82 C83.83 C83.84 C83.85 C83.86
C83.87 C83.88 C83.89 C83.90 C83.91 C83.92 C83.93
C83.94 C83.95 C83.96 C83.97 C83.98 C83.99 C84.00
C84.01 C84.02 C84.03 C84.04 C84.05 C84.06 C84.07
C84.08 C84.09 C84.10 C84.11 C84.12 C84.13 C84.14
C84.15 C84.16 C84.17 C84.18 C84.19 C84.40 C84.41
C84.42 C84.43 C84.44 C84.45 C84.46 C84.47 C84.48
C84.49 C84.60 C84.61 C84.62 C84.63 C84.64 C84.65
C84.66 C84.67 C84.68 C84.69 C84.70 C84.71 C84.72
C84.73 C84.74 C84.75 C84.76 C84.77 C84.78 C84.79
C84.A0 C84.A1 C84.A2 C84.A3 C84.A4 C84.A5 C84.A6
C84.A7 C84.A8 C84.A9 C84.Z0 C84.Z1 C84.Z2 C84.Z3
C84.Z4 C84.Z5 C84.Z6 C84.Z7 C84.Z8 C84.Z9 C84.90
C84.91 C84.92 C84.93 C84.94 C84.95 C84.96 C84.97
C84.98 C84.99 C85.10 C85.11 C85.12 C85.13 C85.14
C85.15 C85.16 C85.17 C85.18 C85.19 C85.20 C85.21
C85.22 C85.23 C85.24 C85.25 C85.26 C85.27 C85.28
C85.29 C85.80 C85.81 C85.82 C85.83 C85.84 C85.85
C85.86 C85.87 C85.88 C85.89 C85.90 C85.91 C85.92
C85.93 C85.94 C85.95 C85.96 C85.97 C85.98 C85.99
C91.00 C91.01 C91.02 Z80.6 Z80.7 Z85.72

Professional Statements and Societal Positions Guidelines

Practice Guidelines and Position Statements

National Comprehensive Cancer Network

Current guidelines from the National Comprehensive Cancer Networki.ii do not include recommendations for chimeric antigen receptor T-cell therapy in certain hematologic cancers, including the central nervous system (e.g., secondary CNS lymphoma) and Hodgkin lymphoma.

Current NCCN guidelines for acute lymphoblastic leukemia (v.1.2020) recommmend (category 2A) tisagenlecleucel as a treatment option for:

  • Philadelphia chromosome-positive individuals 26 years or less in age with refractory disease or 2 or more relapses and failure of 2 tyrosine kinase inhibitors.

  • Philadelphia chromosome-negative individuals 26 years or less in age with refractory disease or 2 or more relapses.

Current Network guidelines for B-cell non-Hodgkin lymphoma (v.4.2019) recommend (category 2A) axicabtagene ciloleucel or tisagenlecleucel as a treatment option for:

  • For histological transformation to diffuse large B-cell lymphoma after multiple lines of prior therapies which include ≥2 chemo-immunotherapy regimens for the indolent or transformed disease.

  • For relapsed or refractory disease diffuse large B-cell lymphoma after multiple lines of prior therapies which include ≥2 chemo-immunotherapy regimens for the indolent or transformed disease.

Footnotes

i Referenced with permission from the NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines®) for Pediatric Acute Lymphoblastic Leukemia V.1.2020 and B-Cell Lymphomas V.4.2019. © National Comprehensive Cancer Network, Inc. 2019. All rights reserved. Accessed September 2, 2019. To view the most recent and complete version of the guideline, go online to NCCN.org.

ii NCCN makes no warranties of any kind whatsoever regarding their content, use or application and disclaims any responsibility for their application or use in any way.

ND Committee Review

Internal Medical Policy Committee 5-19-2020 Adopt policy to replace Adoptive Immunotherapy policy

Disclaimer

Current medical policy is to be used in determining a Member's contract benefits on the date that services are rendered. Contract language, including definitions and specific inclusions/exclusions, as well as state and federal law, must be considered in determining eligibility for coverage. Members must consult their applicable benefit plans or contact a Member Services representative for specific coverage information. Likewise, medical policy, which addresses the issue(s) in any specific case, should be considered before utilizing medical opinion in adjudication. Medical technology is constantly evolving and the Company reserves the right to review and update medical policy periodically.