Billing chart: Blue Cross highlights medical, benefit policy changes

Investigational procedures

Basic benefit and medical policy

External upper limb tremor stimulator

The use of an essential upper limb tremor stimulator for essential tremors is experimental. Its effectiveness in this clinical indication hasn’t been scientifically determined, effective July 1, 2022.

Inclusionary and exclusionary guidelines:

81201-81203, 81210, 81288, 81292-81301, 81317-81319, 81401, 81403, 81406, 81435, 81436

Experimental

Basic benefit and medical policy

Genetic testing for Lynch syndrome and other inherited colon cancer syndromes

The safety and effectiveness of genetic testing for polyposis and non-polyposis cancer syndromes have been established. They may be considered useful diagnostic options for individuals who meet clinical criteria for increased risk of hereditary colorectal cancer.

Inclusionary and exclusionary criteria have been updated, effective July 1, 2022.

Inclusions:

These guidelines refer to the different types of genetic tests available for colorectal cancer, or CRC.

1. Genetic testing of the adenomatous polyposis coli gene, or APC, is established in any of the following:
• At risk^a (first- and second-degree) relatives of patients with familial adenomatous polyposis, or FAP, or attenuated familial adenomatous polyposis, or AFAP, or a known APC variant.
• Patients with a differential diagnosis of attenuated FAP versus MUTYH-associated polyposis, or MAP, versus Lynch syndrome. Whether testing begins with APC variants or screening for mismatch repair MMR variants depends on clinical presentation.

^aDue to the high lifetime risk of cancer of the majority of the genetic syndromes discussed in this policy, “at-risk relatives” primarily refers to first-degree (i.e., siblings, parents, and offspring) and second-degree (i.e., grandparents, aunts, uncles, nieces, nephews, grandchildren and half-siblings) relatives. However, some judgment must be allowed, for example, in the case of a small family pedigree, when extended family members may need to be included in the testing strategy.

Note: It’s recommended that, when possible, initial genetic testing for familial adenomatous polyposis, or FAP, or Lynch syndrome be performed in an affected family member so that testing in unaffected family members can focus on the variant found in the affected family member. If an affected family member isn’t available for testing, testing should begin with an unaffected family member most closely related to an affected family member.

2. Genetic testing of the MUTYH gene is established in all the following:
• Patients with a differential diagnosis of attenuated familial adenomatous polyposis, or FAP, vs. MUTYH-associated polyposis, or MAP, vs. Lynch syndrome
• Negative result for APC gene variants
• Negative family history of no parents or children with FAP is consistent with autosomal recessive MAP

Note: In many cases, genetic testing for MUTYH gene variants should first target the specific variants Y165C and G382D, which account for more than 80% of variants in white populations, and subsequently proceed to sequencing only as necessary. In other ethnic populations, however, proceeding directly to sequencing is appropriate.

3. Genetic testing of MMR genes (MLH1, MSH2, MSH6, PMS2) to determine the carrier status of Lynch syndrome is established in any of the following:
• Patients with colorectal cancer with tumor testing suggesting germline MMR deficiency or meeting clinical criteria for Lynch syndrome
• Patients with endometrial cancer with tumor testing suggesting germline MMR deficiency or meeting clinical criteria for Lynch syndrome
• At-risk^a (first- and second-degree) relatives of patients with Lynch syndrome with a known MMR variant
• Patients with a differential diagnosis of attenuated FAP versus MAP versus Lynch syndrome. Whether testing begins with APC variants or screening for MMR genes depends on clinical presentation
• Patients without colorectal cancer but with a family history meeting the Amsterdam or Revised Bethesda criteria — or documentation of 5% or higher predicted risk of the syndrome on a validated risk prediction model (e.g., MMRpro, PREMM5 or MMRpredict) — when:
• No affected family members have been tested for MMR variants

Notes:

• For patients with colorectal cancer, or CRC, or endometrial cancer being evaluated for Lynch syndrome, the microsatellite instability, or MSI, test, or the immunohistochemical, or IHC, test with or without BRAF gene variant testing, or methylation testing, should be used as an initial evaluation of tumor tissue before mismatch repair MMR gene analysis. Both tests are not necessary. Proceeding to MMR gene sequencing would depend on results of MSI or IHC testing. In particular, IHC testing may help direct which MMR gene likely contains a variant, if any, and may also provide additional information if MMR genetic testing is inconclusive.

• When indicated, genetic sequencing for MMR gene variants should begin with MLH1 and MSH2 genes, unless otherwise directed by the results of IHC testing. Standard sequencing methods won’t detect large deletions or duplications; when MMR gene variants are expected based on IHC or MSI studies, but none are found by standard sequencing, additional testing for large deletions or duplications is appropriate.

4. Genetic testing of the EPCAM gene is established when any of the following major criteria (solid bullets) is met:
• Patients with colorectal cancer, for the diagnosis of Lynch syndrome in one of the following:
• Tumor tissue shows lack of MSH2 protein expression by immunohistochemistry and patient is negative for a MSH2 germline variant
• Tumor tissue shows a high level of microsatellite instability and patient is negative for a germline variant in MSH2, MLH1, PMS2, and MSH6
• At-risk^a (first- and second-degree) relatives of patients with Lynch syndrome with a known pathogenic/likely pathogenic EPCAM variant
• Patients without colorectal cancer but with a family history meeting the Amsterdam or Revised Bethesda criteria, or documentation of 5% or higher predicted risk of the syndrome on a validated risk prediction model (e.g., MMRpro, PREMM5 or MMRpredict) when both of the following are met:
• No affected family members have been tested for MMR variants.
• Sequencing for MMR variants is negative.

The Amsterdam II Clinical Criteria (all criteria must be fulfilled) are the most stringent criteria for defining families at high risk for Lynch syndrome (Vasen et al., 1999):

• Three or more relatives with an associated cancer (colorectal cancer or cancer of the endometrium, small intestine, ureter or renal pelvis)
• One should be a first-degree relative of the other two
• Two or more successive generations affected
• One or more relatives diagnosed before the age of 50
• Familial adenomatous polyposis, or FAP, should be excluded in cases of colorectal carcinoma
• Tumors should be verified by pathologic examination
• Modifications (either one):
• Very small families, which can’t be further expanded, can be considered to have hereditary nonpolyposis colorectal cancer, or HNPCC, with only two colorectal cancers in first-degree relatives if at least two generations have the cancer and at least one case of colorectal cancer was diagnosed by the age of 55 years
• In families with two first-degree relatives affected by colorectal cancer, the presence of a third relative with an unusual early-onset neoplasm or endometrial cancer is sufficient.

The Revised Bethesda Guidelines (fulfillment of any criterion meets guidelines) are less strict than the Amsterdam criteria and are intended to increase the sensitivity of identifying at-risk families (Umar et al., 2004). The Bethesda guidelines are also considered more useful in identifying which patients with colorectal cancer should have their tumors tested for microsatellite instability and/or immunohistochemistry:

• Colorectal carcinoma, or CRC, diagnosed in a patient who is less than 50 years old
• Presence of synchronous or metachronous CRC or other HNPCC-associated tumors,** regardless of age;
• CRC with high microsatellite instability histology diagnosed in a patient less than 60 years old
• CRC diagnosed in one or more first-degree relatives with a Lynch syndrome-associated tumor, with one of the cancers being diagnosed at younger than 50 years of age
• CRC diagnosed in two or more first or second-degree relatives with HNPCC-related tumors,** regardless of age.

**HNPCC-related tumors include colorectal, endometrial, stomach, ovarian, pancreas, ureter and renal pelvis, biliary tract, brain (usually glioblastoma as seen in Turcot syndrome), sebaceous bland adenomas
and keratoacanthomas in Muir-Torre syndrome and carcinoma of the small bowel.

5. Somatic genetic testing for BRAF V600E and MLH1 promoter methylation are established to exclude a diagnosis of Lynch syndrome when:
• MLH1 protein isn’t expressed in a colorectal cancer tumor on immunohistochemical analysis.

6. Genetic testing of SMAD4 and BMPR1A genes are established when any of the following major criteria (solid bullets) is met:
• Individual has a clinical diagnosis of juvenile polyposis syndrome based on the presence of any one of the following:
• At least five juvenile polyps in the colon
• Multiple juvenile polyps throughout the gastrointestinal tract
• Any number of juvenile polyps in a person with a known family history of juvenile polyps
• Individual is an at-risk relative of a patient suspected of or diagnosed with juvenile polyposis syndrome.

7. Genetic testing for STK11 gene variants is established when any of the following major criteria (solid bullets) is met:
• Individual has a clinical diagnosis of Peutz-Jeghers syndrome based on the presence of any two of the following secondary criteria:
• Presence of two or more histologically confirmed Peutz-Jeghers polyps of the small intestine
• Characteristic mucocutaneous pigmentation of the mouth, lips, nose, eyes, genitalia or fingers
• Family history of Peutz-Jeghers syndrome
• Individual is an at-risk^a relative of a patient suspected of or diagnosed with Peutz-Jeghers syndrome.

Pre- and post-test genetic counseling is established as an adjunct to genetic testing.

Note: Genetic counseling is primarily aimed at patients who are at risk for inherited disorders and experts recommend formal genetic counseling in most cases when genetic testing for an inherited condition is considered. The interpretation of the results of genetic tests and the understanding of risk factors can be very difficult and complex. Therefore, genetic counseling will assist individuals in understanding the possible benefits and harms of genetic testing, including the possible effect of the information on the individual’s family. Genetic counseling may alter the utilization of genetic testing substantially and may reduce inappropriate testing. Genetic counseling should be performed by an individual with experience and expertise in genetic medicine and genetic testing methods.

Exclusions:

Testing for germline APC gene variants for inherited CRC syndromes is considered experimental in all other situations.

Testing for germline MUTYH gene variants for inherited CRC syndromes is considered experimental in all other situations.

Testing for germline MMR gene variants for inherited CRC syndromes is considered experimental in all other situations.

Testing for somatic BRAF V600E or MLH1 promoter methylation to exclude a diagnosis of Lynch syndrome is considered experimental in all other situations.

Testing for germline SMAD4 and BMPR1A gene variants for inherited CRC syndromes is considered experimental in all other situations.

Testing for germline STK11 gene variants for inherited CRC syndromes is considered experimental in all other situations.

Genetic testing for all other genes for an inherited CRC syndrome is considered experimental.

81538, 84999**

Basic benefit and medical policy

Proteomic testing for non-small cell lung cancer

The use of proteomic testing such as VeriStrat^® is considered experimental. The evidence is insufficient to determine that the technology results in an improvement in the net health outcome.

Experimental is effective May 1, 2022.

Inclusionary and exclusionary guidelines:

Not applicable

A9699

Basic benefit and medical policy

Pluvicto (lutetium Lu 177 vipivotide tetraxetan)

Pluvicto (lutetium Lu 177 vipivotide tetraxetan) is payable for its FDA-approved indications, effective March 23, 2022.

Pluvicto is a radioligand therapeutic agent indicated for the treatment of adult patients with prostate-specific membrane antigen, or PSMA, positive metastatic castration-resistant prostate cancer, or mCRPC, who have been treated with androgen receptor pathway inhibition and taxane-based chemotherapy.

Dosage and administration:

• Select patients for treatment using Locametz^® or an approved PSMA-11 imaging agent based on PSMA expression in tumors.
• Recommended dosage: Administer 7.4 GBq (200 mCi) every six weeks for up to six doses.
• Dose interruption, reduction or permanent discontinuation may be required due to adverse reactions.

Dosage forms and strengths:

Injection: 1,000 MBq/mL (27 mCi/mL) in a single-dose vial

Pluvicto (lutetium Lu 177 vipivotide tetraxetan) isn’t a benefit for URMBT.

C9399
J3490
J3590
J9999

Basic benefit and medical policy

Releuko (filgrastim-ayow)

Releuko (filgrastim-ayow) is payable for the FDA-approved indications, effective Feb. 25, 2022.

Releuko is a leukocyte growth factor indicated to:

• Decrease the incidence of infection‚ as manifested by febrile neutropenia‚ in patients with nonmyeloid malignancies receiving myelosuppressive anti-cancer drugs associated with a significant incidence of severe neutropenia with fever.
• Reduce the time to neutrophil recovery and the duration of fever, following induction or consolidation chemotherapy treatment of patients with acute myeloid leukemia, or AML.
• Reduce the duration of neutropenia and neutropenia-related clinical sequelae‚ e.g.‚ febrile neutropenia, in patients with nonmyeloid malignancies undergoing myeloablative chemotherapy followed by bone marrow transplantation, or BMT.
• Reduce the incidence and duration of sequelae of severe neutropenia‚ (e.g., fever‚ infections‚ oropharyngeal ulcers) in symptomatic patients with congenital neutropenia‚ cyclic neutropenia or idiopathic neutropenia.

Dosage and administration:

• Patients with cancer receiving myelosuppressive chemotherapy or induction or consolidation chemotherapy for AML: Recommended starting dose is 5 mcg/kg/day subcutaneous injection, short intravenous infusion (15 to 30 minutes) or continuous intravenous infusion.
• Patients with cancer undergoing bone marrow transplantation: 10 mcg/kg/day given as an intravenous infusion no longer than 24 hours.
• Patients with congenital neutropenia: Recommended starting dose is 6 mcg/kg subcutaneous injection twice daily.
• Patients with cyclic or idiopathic neutropenia: Recommended starting dose is 5 mcg/kg subcutaneous injection daily.
• Direct administration of less than 0.3 mL (180 mcg) using Releuko prefilled syringe isn’t recommended due to potential for dosing errors.

Dosage forms and strengths:

Vial:

• Injection: 300 mcg/mL in a single-dose vial
• Injection: 480 mcg/1.6 mL in a single-dose vial

Prefilled syringe:

• Injection: 300 mcg/0.5 mL in a single-dose prefilled syringe
• Injection: 480 mcg/0.8 mL in a single-dose prefilled syringe

Releuko (filgrastim-ayow) isn’t a benefit for URMBT.

J0741

Basic benefit and medical policy

Cabenuva (cabotegravir extended-release injectable suspension; rilpivirine extended-release injectable suspension)

Effective March 23, 2022, Cabenuva (cabotegravir extended-release injectable suspension; rilpivirine extended-release injectable suspension) is covered for the following updated FDA-approved indications:

Cabenuva, a two-drug co-packaged product of cabotegravir, an HIV-1 integrase strand transfer inhibitor, or INSTI, and rilpivirine, an HIV-1 non-nucleoside reverse transcriptase inhibitor, or NNRTI, is indicated as a complete regimen for the treatment of HIV-1 infection in adults and adolescents 12 and older and weighing at least 35 kg to replace the current antiretroviral regimen in those who are virologically suppressed (HIV-1 RNA <50 copies/mL) on a stable antiretroviral regimen with no history of treatment failure and with no known or suspected resistance to either cabotegravir or rilpivirine.

J3490
J3590

Basic benefit and medical policy

Vabysmo (faricimab-svoa)

Effective Jan. 1, 2022, Vabysmo (faricimab-svoa) is covered for the following FDA-approved indications:

Vabysmo is a vascular endothelial growth factor, or VEGF, and angiopoietin-2, or Ang-2, inhibitor indicated for the treatment of patients with:

• Neovascular (wet) age-related macular degeneration, or nAMD 
• Diabetic macular edema, or DME

Dosage and administration (for intravitreal injection):

Neovascular (wet) age-related macular degeneration, or nAMD

• The recommended dose for Vabysmo is 6 mg (0.05 mL of 120 mg/mL solution) administered by intravitreal injection every four weeks (approximately every 28 ± 7 days, monthly) for the first four doses, followed by optical coherence tomography and visual acuity evaluations eight and 12 weeks later to inform whether to give a 6 mg dose via intravitreal injection on one of the following three regimens: 1) Weeks 28 and 44; 2) Weeks 24, 36 and 48; or 3) Weeks 20, 28, 36 and 44. Although additional efficacy wasn’t demonstrated in most patients when Vabysmo was dosed every four weeks compared to every eight weeks, some patients may need every four week (monthly) dosing after the first four doses. Patients should be assessed regularly.

Diabetic macular edema, or DME

• Vabysmo is recommended to be dosed by following one of these two dose regimens: 1) 6 mg (0.05 mL of 120 mg/mL solution) administered by intravitreal injection every four weeks approximately every 28 days ± 7 days, monthly) for at least four doses. If after at least four doses, resolution of edema based on the central subfield thickness, or CST, of the macula as measured by optical coherence tomography is achieved, then the interval of dosing may be modified by extensions of up to four week interval increments or reductions of up to eight week interval increments based on CST and visual acuity evaluations through week 52; or 2) 6 mg dose of Vabysmo can be administered every four weeks for the first six doses, followed by 6 mg dose via intravitreal injection at intervals of every eight weeks (two months) over the next 28 weeks. Although additional efficacy wasn’t demonstrated in most patients when Vabysmo was dosed every four weeks compared to every eight weeks, some patients may need every four-week (monthly) dosing after the first four doses. Patients should be assessed regularly. 

Dosage forms and strengths:

Injection: 120 mg/mL solution in a single-dose vial

This drug isn’t a benefit for URMBT.

J9022

Basic benefit and medical policy

Tecentriq (atezolizumab)

Tecentriq (atezolizumab) is no longer FDA approved for the following indication:

Triple-negative breast cancer, or TNBC, in combination with paclitaxel protein-bound for the treatment of adult patients with unresectable locally advanced or metastatic TNBC whose tumors express PD-L1 (PD-L1 stained tumor-infiltrating immune cells [IC] of any intensity covering ≥ 1% of the tumor area), as determined by an FDA-approved test.

J9047

Basic benefit and medical policy

Kyprolis (carfilzomib)

Kyprolis (carfilzomib) is considered established when criteria are met, effective Nov. 30, 2021.

Kyprolis (carfilzomib) is payable for the following updated indications:

• Kyprolis (carfilzomib) is a proteasome inhibitor that is indicated for the following:
• For the treatment of adult patients with relapsed or refractory multiple myeloma who have received one to three lines of therapy in combination with Daratumumab and hyaluronidase-fihj and dexamethasone

Dosage and administration:

Regimen: Kyprolis and Dexamethasone, or Kd, or          
Kyprolis, Daratumumab and Dexamethasone, or DKd, or Daratumumab and hyaluronidase-fihj and Dexamethasone, or DKd

Dosage: 20/70mg/m2 once weekly                                     

Infusion time: 30 minutes

J9271

Basic benefit and medical policy

Keytruda (pembrolizumab)

Effective March 21, 2022, Keytruda (pembrolizumab) is covered for the following updated FDA-approved indications:

Keytruda (pembrolizumab) is a programmed death receptor-1 (PD-1)-blocking antibody indicated for:

Endometrial carcinoma:

• In combination with lenvatinib, for the treatment of patients with advanced endometrial carcinoma that isn’t MSI-H or dMMR, who have disease progression following prior systemic therapy and aren’t candidates for curative surgery or radiation.
• As a single agent, for the treatment of patients with advanced endometrial carcinoma that is MSI-H or dMMR, as determined by an FDA-approved test, who have disease progression following prior systemic therapy in any setting and aren’t candidates for curative surgery or radiation.

Triple-negative breast cancer, or TNBC:     

• For the treatment of patients with high-risk early-stage TNBC in combination with chemotherapy as neoadjuvant treatment, then continued as a single agent as adjuvant treatment after surgery
• In combination with chemotherapy, for the treatment of patients with locally recurrent unresectable or metastatic TNBC whose tumors express PD-L1 (Combined Positive Score [CPS] ≥10) as determined by an FDA-approved test

Renal cell carcinoma, or RCC:

• In combination with axitinib, for the first-line treatment of patients with advanced RCC
• In combination with lenvatinib, for the first-line treatment of adult patients with advanced RCC
• For the adjuvant treatment of patients with RCC at intermediate-high or high risk of recurrence following nephrectomy, or following nephrectomy and resection of metastatic lesions