Comprehensive molecular profiling (also referred to as comprehensive genomic profiling) is a type of test that involves a combination of laboratory methodologies to detect genetic alterations and biomarkers in bone marrow or tumor tissue to aid in the management of hematologic malignancies and solid tumors. Techniques can vary from test to test and may include:

• Description Chromogenic in situ hybridization (CISH)
• Fluorescence in situ hybridization (FISH)
• Fragment analysis
• Immunohistochemistry (IHC)
• Next-generation sequencing (NGS)

Comprehensive Molecular Profiling for Hematologic Malignancies and Solid Tumors

Effective Date: 01/01/2024

Revision Date: 01/01/2024

Review Date: 06/22/2023

Policy Number: HUM-0595-007

Page: 2 of 23

Humana's documents are updated regularly online. When printed, the version of this document becomes uncontrolled. Do not rely on printed copies for the most up-to-date version. Refer to Medical and Pharmacy Coverage Policies to verify that this is the current version before utilizing.

• Polymerase chain reaction (PCR)
• Pyro sequencing (PyroSeq)
• Sanger sequencing
• Whole exome sequencing (WES)
• Whole genome sequencing (WGS)
• Whole transcriptome sequencing

Testing results may aid in diagnosis, prognosis, monitoring, surveillance, guide treatment decisions and determine eligibility for participation in clinical trials. Some assays are purportedly used to provide information regarding microsatellite instability (MSI), measurable (minimal) residual disease (MRD) and tumor mutational burden (TMB).

For information regarding TMB, please refer to Pharmacogenomics and Companion Diagnostics Medical Coverage Policy.

Comprehensive molecular profiling may be utilized for the detection of MRD which is a term used for hematologic malignancies and is defined as the small number of cancer cells that remain in the body following treatment. Examples include ClonoSEQ MRD Detection and MyMRD Gene Panel Assay.

LungOI is an artificial-intelligence (AI)-based molecular profiling that uses a digitized biopsy image and is proposed for the diagnosis of lung cancer. (Refer to Coverage Limitations section)

Molecular profiling in conjunction with in vitro chemoresistance and chemosensitivity assays has been proposed to guide treatment decisions. (Refer to Coverage Limitations section)

For information regarding in vitro chemoresistance and chemosensitivity assays, please refer to In Vitro Chemoresistance and Chemosensitivity Assays Medical Coverage Policy.

For information regarding FoundationOne CDx, please refer to Pharmacogenomics and Companion Diagnostics Medical Coverage Policy.

Comprehensive Molecular Profiling for Hematologic Malignancies and Solid Tumors

Effective Date: 01/01/2024

Revision Date: 01/01/2024

Review Date: 06/22/2023

Policy Number: HUM-0595-007

Page: 3 of 23

Humana's documents are updated regularly online. When printed, the version of this document becomes uncontrolled. Do not rely on printed copies for the most up-to-date version.

Refer to Medical and Pharmacy Coverage Policies to verify that this is the current version before utilizing.For information regarding FoundationOne Liquid, please refer to Liquid Biopsy Medical Coverage Policy.

For information regarding Oncomine Dx Target Test for cholangiocarcinoma, please refer to Genetic Testing for Diagnosis and Monitoring of Cancer Medical Coverage Policy.

For information regarding genetic testing for the following, please refer to Genetic Testing Medical Coverage Policy:

• DNA banking or preservation
• General population screening
• Individual 17 years of age or younger for adult-onset conditions
• Interpretation and reporting for molecular pathology procedure
• Polygenic risk score (PRS) and single nucleotide polymorphisms (SNPs)
• Repeat germline or somatic genetic testing
• Retrieved archival tissue

Humana recognizes that the field of genetic testing is rapidly changing and that other tests may become available.

Coverage Determination

Any state mandates for comprehensive molecular profiling for hematologic malignancies and solid tumors take precedence over this medical coverage policy.

Genetic testing may be excluded by certificate. Please consult the member’s individual certificate regarding Plan coverage.

Apply General Criteria for Genetic and Pharmacogenomics Tests when disease- or gene-specific criteria are not available on a medical coverage policy. For information regarding general criteria for genetic tests, please refer to Genetic Testing Medical Coverage Policy.

Comprehensive Molecular Profiling for Hematologic Malignancies

Humana members may be eligible under the Plan for comprehensive molecular profiling consisting of 50 or fewer genes (81450, 81451) for acute myeloid leukemia when the following criteria are met:

• For diagnostic workup; OR
• Relapsed or refractory disease (NOTE: testing may be repeated at each relapse or progression); OR
• To determine clinical trial eligibility

Comprehensive Molecular Profiling for Solid Tumors

Humana members may be eligible under the Plan for comprehensive molecular profiling (consisting of 50 or fewer genes) for solid tumors (81445, 81449) when the following criteria are met:

• Diagnosed with recurrent, relapsed, refractory, metastatic or advanced stage III or IV cancer; AND
• Has not previously received comprehensive molecular profiling for the same tumor type; AND
• Treatment with anticancer therapy is being considered

Measurable (Minimal) Residual Disease

Humana members may be eligible under the Plan for ClonoSEQ MRD Detection (0364U) for the assessment of MRD for the following indications when criteria are met:

• Acute lymphoblastic leukemia; AND
  • Prior to treatment for baseline assessment; OR
  • Assessment of molecular relapse or persistent low-level disease burden; OR
  • Following induction or consolidation; OR
  • Surveillance; OR
• Chronic lymphoblastic leukemia; AND
  • Prior to treatment for baseline assessment; OR
  • Following treatment; OR

Comprehensive Molecular Profiling for Hematologic Malignancies and Solid Tumors Effective Date: 01/01/2024 Revision Date: 01/01/2024 Review Date: 06/22/2023 Policy Number: HUM-0595-007 Page: 5 of 23

Humana's documents are updated regularly online. When printed, the version of this document becomes uncontrolled. Do not rely on printed copies for the most up-to-date version.

Refer to Medical and Pharmacy Coverage Policies to verify that this is the current version before utilizing.

• Multiple myeloma; AND
  • Prior to treatment for baseline assessment; OR
  • Suspected complete response following induction, high-dose therapy/autologous stem cell transplant, consolidation or maintenance

Humana members may be eligible under the Plan for MyMRD Gene Panel Assay (0171U) for the assessment of MRD for acute myeloid leukemia when the following criteria are met:

• Prior to treatment for baseline assessment; OR
• Following initial induction; OR
• Before allogenic hematopoietic cell transplantation

Note: The criteria for comprehensive molecular profiling for hematologic malignancies and solid tumors are not consistent with the Medicare National Coverage Policy and therefore may not be applicable to Medicare members. Refer to the CMS website for additional information.

Coverage Limitations

Humana members may NOT be eligible under the Plan for comprehensive molecular profiling for any indications or tests other than those listed above including, but may not be limited to:

• ACTOnco IVD Assay
• Adjunct to in vitro chemoresistance and chemosensitivity assays
• Altera Tumor Genomic Profiling (offered in conjunction with Signatera; refer to Liquid Biopsy Medical Coverage Policy)
• Caris Molecular Intelligence (MI) including, but not limited to:
  • Caris MI Profile Comprehensive Testing
  • Caris MI Tumor Seek
• CureMatch (0794T)
• FoundationOne Heme
• Guardant360 TissueNext (0334U)
• Integrated Mutation Profiling of Actionable Cancer Targets (MSK-IMPACT) (0048U)
• LungOI (0414U)
• Moffitt STAR (Solid Tumor Actionable Result)
• Myriad Precise Tumor
• NeoTYPE Cancer Profiles including, but not limited to:
  • NeoTYPE Breast Tumor Profile
  • NeoTYPE Broad Reach Tumor Profiles including Hematologic Disease Profile and Solid Tumor Profile
  • NeoTYPE Cancer Profile (offered as a reflex test for CancerTYPE ID; for information regarding CancerTYPE ID, please refer to Gene Expression Profiling for Cancer Indications Medical Coverage Policy)
  • NeoTYPE CLL Prognostic Profiling
  • NeoTYPE Next-Gen Cancer Specific Profiles including Hematologic Disease Profile and Solid Tumor Profile
• OmniSeq panels including, but not limited to:
  • OmniSeq Advance
  • OmniSeq Comprehensive
  • OmniSeq INSIGHT
  • OmniSeq Target

Comprehensive Molecular Profiling for Hematologic Malignancies and Solid Tumors Effective Date: 01/01/2024 Revision Date: 01/01/2024 Review Date: 06/22/2023 Policy Number: HUM-0595-007 Page: 6 of 23

Humana's documents are updated regularly online. When printed, the version of this document becomes uncontrolled. Do not rely on printed copies for the most up-to-date version.

Refer to Medical and Pharmacy Coverage Policies to verify that this is the current version before utilizing.

Comprehensive Molecular Profiling for Hematologic Malignancies and Solid Tumors Effective Date: 01/01/2024 Revision Date: 01/01/2024 Review Date: 06/22/2023 Policy Number: HUM-0595-007 Page: 7 of 23

Humana's documents are updated regularly online. When printed, the version of this document becomes uncontrolled. Do not rely on printed copies for the most up-to-date version.

Refer to Medical and Pharmacy Coverage Policies to verify that this is the current version before utilizing.

• OncoExTra (formerly known as Oncomap ExTra and GEM ExTra) (0329U)
• ONcoGxOne
• Oncomap (formerly known as Oncotype MAP Pan-Cancer Tissue Test and Paradigm Cancer Diagnostic [PCDx]) (0244U)
• OncoPlus Universal Cancer Mutation Analysis PanelPCDx
• PGDx elio tissue complete (0250U)
• Prima panels including, but may not be limited to:
  • Prima Comprehensive Tumor Panel
  • Prima Somatic Cancer Mutation Panel
• Quest Diagnostics Solid Tumor Expanded Panel (0379U)
• StrataNGS
• Strata Select (0391U)
• SureSeq CLL + CNV Panel
• Targeted DNA and RNA genomic sequence analysis panel of 51 or more genes associated with solid organ or hematolymphoid neoplasm (CPT code 81455, 81456)
• Tempus panels including, but may not be limited to, Tempus xT
• TheraMap panels including, but may not be limited to:
  • TheraMap: Myeloid Malignancies
  • TheraMap: Solid Tumor
  • TheraMap: Solid Tumor with Reflex

Comprehensive Molecular Profiling for Hematologic Malignancies and Solid Tumors

Effective Date: 01/01/2024

Revision Date: 01/01/2024

Review Date: 06/22/2023

Policy Number: HUM-0595-007

Page: 8 of 23

Humana's documents are updated regularly online. When printed, the version of this document becomes uncontrolled. Do not rely on printed copies for the most up-to-date version. Refer to Medical and Pharmacy Coverage Policies to verify that this is the current version before utilizing.

These are considered experimental/investigational as they are not identified as widely used and generally accepted for the proposed uses as reported in nationally recognized peer-reviewed medical literature published in the English language.

Background

Additional information about cancer may be found from the following websites:

• American Cancer Society
• National Library of Medicine

Medical Alternatives

Physician consultation is advised to make an informed decision based on an individual's health needs.

Humana may offer a disease management program for this condition. The member may call the number on his/her identification card to ask about our programs to help manage his/her care.

Any CPT, HCPCS or ICD codes listed on this medical coverage policy are for informational purposes only. Do not rely on the accuracy and inclusion of specific codes. Inclusion of a code does not guarantee coverage and or reimbursement for a service or procedure.