Notification



Notification Issue Date:



Medicare Advantage Policy

Title:Siltuximab (Sylvant®)
Policy #:MA08.006f

This policy is applicable to the Company’s Medicare Advantage products only. Policies that are applicable to the Company’s commercial products are accessible via a separate commercial policy database.


The Company makes decisions on coverage based on the Centers for Medicare and Medicaid Services (CMS) regulations and guidance, benefit plan documents and contracts, and the member’s medical history and condition. If CMS does not have a position addressing a service, the Company makes decisions based on Company Policy Bulletins. Benefits may vary based on contract, and individual member benefits must be verified. The Company determines medical necessity only if the benefit exists and no contract exclusions are applicable. Although the Medicare Advantage Policy Bulletin is consistent with Medicare’s regulations and guidance, the Company’s payment methodology may differ from Medicare.

When services can be administered in various settings, the Company reserves the right to reimburse only those services that are furnished in the most appropriate and cost-effective setting that is appropriate to the member’s medical needs and condition. This decision is based on the member’s current medical condition and any required monitoring or additional services that may coincide with the delivery of this service.


This Policy Bulletin document describes the status of CMS coverage, medical terminology, and/or benefit plan documents and contracts at the time the document was developed. This Policy Bulletin will be reviewed regularly and be updated as Medicare changes their regulations and guidance, scientific and medical literature becomes available, and/or the benefit plan documents and/or contracts are changed.



Policy

Coverage is subject to the terms, conditions, and limitations of the member's Evidence of Coverage.

The Company reserves the right to reimburse only those services that are furnished in the most appropriate and cost-effective setting that is appropriate to the member’s medical needs and condition.

MEDICALLY NECESSARY

Siltuximab (Sylvant®) is considered medically necessary and, therefore, covered for individuals with Castleman’s disease, when all of the following criteria are met:
  • Siltuximab (Sylvant®) is used for one of the following types of Castleman’s disease:
    • Multicentric Castleman’s disease (MCD) with no organ failure, as treatment for one of the following:
      • Primary treatment
      • Relapsed disease
      • If no response to primary therapy
    • Unicentric Castleman’s disease (UCD) as second-line therapy for relapsed or refractory disease
  • Individual is human immunodeficiency virus (HIV)--negative and human herpesvirus-8 (HHV-8)--negative.
  • Individual meets the following relevant documented laboratory requirements before the administration of the initial and subsequent doses:
    • First dose:
      • Absolute Neutrophil Count (ANC) 1.0 X 109/L or greater
      • Platelets 75 X 109/L or greater
      • Hemoglobin less than 17 g/dL
    • Subsequent doses:
      • ANC 1.0 X 109/L or greater
      • Platelets 50 X 109/L or greater
      • Hemoglobin less than 17 g/dL

EXPERIMENTAL/INVESTIGATIONAL

All other uses for siltuximab (Sylvant®) are considered experimental/investigational and, therefore, not covered unless the indication is supported as an accepted off-label use, as defined in the Company medical policy on off-label coverage for prescription drugs and biologics.

REQUIRED DOCUMENTATION

The individual's medical record must reflect the medical necessity for the care provided. These medical records may include, but are not limited to: records from the professional provider's office, hospital, nursing home, home health agencies, therapies, and test reports.

The Company may conduct reviews and audits of services to our members, regardless of the participation status of the provider. All documentation is to be available to the Company upon request. Failure to produce the requested information may result in a denial for the drug.
Policy Guidelines

There is no Medicare coverage determination addressing siltuximab (Sylvant®); therefore, the Company policy is applicable.

Certain drugs are available through either the member's medical benefit (Part B benefit) or pharmacy benefit (Part D benefit), depending on how the drug is prescribed, dispensed, or administered. This medical policy only addresses instances when siltuximab (Sylvant®) is covered under a member's medical benefit (Part B benefit). It does not address instances when siltuximab (Sylvant®) is covered under a member’s pharmacy benefit (Part D benefit).

DRUG ADMINISTRATION

Siltuximab (Sylvant®) is administered as an intravenous infusion over a 1-hour period. The safety and effectiveness of siltuximab (Sylvant®) have not been established in the pediatric population.

BENEFIT APPLICATION

Subject to the terms and conditions of the applicable Evidence of Coverage, siltuximab (Sylvant®) is covered under the medical benefits of the Company’s Medicare Advantage products when the medical necessity criteria listed in this medical policy are met.

US FOOD AND DRUG ADMINISTRATION (FDA) STATUS

Siltuximab (Sylvant®) was approved by the FDA on April 22, 2014 for the treatment of multicentric Castleman’s disease (MCD) in individuals who are human immunodeficiency virus (HIV)-negative and human herpesvirus-8 (HHV-8)-negative. The safety and efficacy of siltuximab (Sylvant®) have not been established in pediatric individuals.

Description

Castleman's disease is rare blood disorder characterized by the overproduction of lymphocytes, leading to enlarged lymph nodes. The development of Castleman's disease is thought to be related to an overproduction of interleukin-6 (IL-6), a substance normally produced by cells within the lymph nodes. Although Castleman's disease is not malignant in nature, those with its diagnosis have an increased risk of developing lymphoma.

HISTOLOGY

There are three main histological subtypes of affected lymph nodes: hyaline vascular subtype, plasma cell subtype, and mixed cellularity subtype.

In the hyaline vascular subtype, most individuals are asymptomatic; however, some may develop enlarged lymph nodes, and treatment is surgical removal of these lymph nodes. For the plasma cell subtype, individuals may experience symptoms such as fever, weight loss, skin rash, anemia, and hypergammaglobulinemia. The plasma cell subtype has a poorer prognosis, with an overall mortality of 50% and a median survival of 26 months. Finally, the mixed cellularity subtype has features of both hyaline vascular and plasma cell subtypes, although, clinically, mixed cellularity behaves more like the plasma cell subtype than the hyaline vascular subtype.

CATEGORIES

There are two categories of Castleman’s disease, based on the number of anatomic sites affected: unicentric Castleman's disease (UCD) and multicentric Castleman's disease (MCD).

UNICENTRIC CASTLEMAN'S DISEASE (UCD)
Unicentric Castleman’s disease (UCD) is characterized by enlarged lymph nodes that are localized to one area of the lymphatic system, mainly the chest. The hyaline vascular subtype accounts for 80-90% of all cases of UCD. UCD can occur at any age, but is generally diagnosed at a median age of 35 years. It is found equally in men and women. UCD has a 90-95% cure rate with surgical resection. In a systematic review by Talat et al (2012), after complete resection, the disease-free survival rates at 3 and 5 years were 90% and 81%, respectively.

MULTICENTRIC CASTLEMAN'S DISEASE (MCD)
Multicentric Castleman’s disease (MCD) is characterized by enlarged lymph nodes that are widespread throughout the lymphatic system. The plasma cell variant subtype accounts for 75-90% of all cases of MCD. MCD affects men and woman almost equally, and usually at a median age range of 50 to 65 years old, although the age range is younger in those who are HIV-positive. The onset of MCD varies from slow onset over a few years to acute illness. The most common symptoms associated with MCD include fever, peripheral lymphadenopathy, hepatosplenomegaly, night sweats, weight loss, weakness, fatigue, and edema.

MCD has been associated with other conditions such as POEMS syndrome (polyneuropathy, organomegaly, endocrinopathy, monoclonal gammopathy, and skin changes), Kaposi's sarcoma, and malignant lymphoma. Unlike UCD, MCD is strongly associated with immunosuppression and human herpesvirus-8 (HHV-8) infection. Also, individuals infected with human immunodeficiency virus (HIV) are at an increased risk of developing MCD.

HHV-8 (or Kaposi sarcoma herpesvirus [KSHV]) is found in nearly all individuals who are HIV-positive and develop MCD, and in up to 60% of individuals who are HIV-negative. HHV-8 is thought to synthesize its own virally produced excess IL-6. In individuals who are not infected with HHV-8, it is thought that excess IL-6 may be caused by a genetic mutation in the IL-6 promotor gene.

MCD may be managed by drugs that target the IL-6--producing cells, such as rituximab (Rituxan®) or siltuximab (Sylvant®). Siltuximab (Sylvant®) is a human-mouse chimeric monoclonal antibody that exerts its affects by binding to IL-6 and preventing it from binding to IL-6 receptors. On April 22, 2014, the US Food and Drug Administration (FDA) approved siltuximab (Sylvant®) for the treatment of MCD in individuals who are HIV-negative and HHV-8-negative. Siltuximab (Sylvant®) was not studied in those with HIV-positive or HHV-8--positive MCD because siltuximab (Sylvant®) did not bind to virally produced IL-6 in a nonclinical study.

PEER-REVIEWED LITERATURE

SUMMARY
The safety and effectiveness of siltuximab (Sylvant®) was demonstrated in a Phase 2, multinational, randomized, double-blind, placebo-controlled study of 79 individuals with MCD who received either siltuximab (Sylvant®) plus best supportive care or placebo plus best supportive care until treatment failure or until an unacceptable toxicity occurred. Each group had similar histological subtypes: 33% hyaline vascular, 23% plasma cell, 44% mixed cellularity. Siltuximab (Sylvant®) produced a persistent durable tumor and symptomatic response of at least 18 weeks duration in significantly more individuals compared with placebo (34% vs 0%). Siltuximab (Sylvant®) produced a longer median time to treatment failure in significantly more individuals compared with placebo (time not reached vs 134 days). Siltuximab (Sylvant®) also produced statistically significant improvements in anemia compared with placebo (61% vs 0%). No individuals with hyaline vascular histology achieved the outcome. Overall survivor results were not mature at the time of the study analysis; however, the 1-year survival rates were 100% for siltuximab (Sylvant®) group and 92% for placebo group.

OFF-LABEL INDICATIONS

There may be additional indications contained in the Policy section of this document due to evaluation of criteria highlighted in the Company’s off-label policy, and/or review of clinical guidelines issued by leading professional organizations and government entities.
References

American Hospital Formulary Service (AHFS). Drug Info 2020. Siltuximab. [Lexicomp Online Web site]. 10/30/15. Available at: http://online.lexi.com/lco/action/home [via subscription only]. Accessed January 17, 2020.

El-Osta HE, Kurzrock R. Castleman's disease: from basic mechanisms to molecular therapeutics. Oncologist. 2011;16(4):497-511.

Elsevier’s Clinical Pharmacology Compendium. Siltuximab. 01/30/17. [Clinical Key Web site]. Available at: https://www.clinicalkey.com/pharmacology/ [via subscription only]. Accessed January 17, 2020.

Fajgenbaum DC. HHV-8-associated multicentric castleman's disease. [UpToDate]. updated 01/16/2020. Available at: http://www.uptodate.com/contents/multicentric-castlemans-disease?source=search_result&search=castleman%27s&selectedTitle=2%7E48. Accessed January 17, 2020.

Fajgenbaum DC. Unicentric castleman's disease. [UpToDate]. updated 01/16/2020. Available at: http://www.uptodate.com/contents/unicentric-castlemans-disease. Accessed January 17, 2020.

Lexi-Drugs Compendium. Siltuximab. 12/20/2019. [Lexicomp Online Web site]. Available at: http://online.lexi.com/lco/action/home [via subscription only]. Accessed January 17, 2020.

Mylona EE, Baraboutis IG, Lekakis LJ, et al. Multicentric Castleman's disease in HIV infection: a systematic review of the literature. AIDS Rev. 2008;10(1):25-35.

National Comprehensive Cancer Network (NCCN). NCCN Clinical Practice Guidelines in Oncology - B-Cell Lymphomas. V.7.2019. 12/18/2019. [NCCN Web site]. Available at: https://www.nccn.org/professionals/physician_gls/pdf/b-cell.pdf [via free subscription]. Accessed January 17, 2020.

National Comprehensive Cancer Network (NCCN). NCCN Drugs & Biologics Compendium. Siltuximab (Sylvant®). [NCCN Web site]. 2020. Available at: http://www.nccn.org/professionals/drug_compendium/content/contents.asp [via subscription only]. Accessed January 17, 2020.

National Organization of Rare Diseases (NORD). Castleman’s Disease.Updated 2017. Available at: https://rarediseases.org/rare-diseases/castlemans-disease/ . Accessed January 17, 2020.

Siltuximab (Sylvant®). package insert. 05/2018. JANSSEN BIOTECH; Horsham, PA. Available at: http://www.sylvant.com/. Accessed January 17, 2020.

Soumerai JD, Sohani AR, Abramson JS. Diagnosis and management of Castleman disease. Cancer Control. 2014 Oct;21(4):266-78.

Talat N, Belgaumkar AP, Schulte KM. Surgery in Castleman's disease: a systematic review of 404 published cases. Ann Surg. 2012 Apr;255(4):677-84.

Truven Health Analytics, Inc. Micromedex® DrugDex® Compendium. Siltuximab (Sylvant®). Micromedex® Web site]. 11/06/2019. Available at: https://www.micromedexsolutions.com/micromedex2/librarian/ssl/true [via subscription only]. Accessed January 17, 2020.

US Food and Drug Administration (FDA). Center for Drug evaluation and Research. Drugs @FDA. Siltuximab (Sylvant®) package insert [FDA Website] (12/2019). Available at: https://www.accessdata.fda.gov/scripts/cder/daf/. Accessed January 17, 2020.

van Rhee F, Fayad L, Voorhees P, et al. Siltuximab, a novel anti-interleukin-6 monoclonal antibody, for Castleman's disease. J Clin Oncol. 2010 Aug 10;28(23):3701-8.

van Rhee F, Wong RS, Munshi N, et al. Siltuximab for multicentric Castleman's disease: a randomised, double-blind, placebo-controlled trial. Lancet Oncol. 2014 Aug;15(9):966-74.


Coding

Inclusion of a code in this table does not imply reimbursement. Eligibility, benefits, limitations, exclusions, precertification/referral requirements, provider contracts, and Company policies apply.

The codes listed below are updated on a regular basis, in accordance with nationally accepted coding guidelines. Therefore, this policy applies to any and all future applicable coding changes, revisions, or updates.

In order to ensure optimal reimbursement, all health care services, devices, and pharmaceuticals should be reported using the billing codes and modifiers that most accurately represent the services rendered, unless otherwise directed by the Company.

The Coding Table lists any CPT, ICD-9, ICD-10, and HCPCS billing codes related only to the specific policy in which they appear.

CPT Procedure Code Number(s)

N/A


Professional and outpatient claims with a date of service on or before September 30, 2015, must be billed using ICD-9 codes. Professional and outpatient claims with a date of service on or after October 1, 2015, must be billed using ICD-10 codes.

Facility/Institutional inpatient claims with a date of discharge on or before September 30, 2015, must be billed with ICD-9 codes. Facility/Institutional inpatient claims with a date of discharge on or after October 1, 2015, must be billed with ICD-10 codes.


ICD - 10 Procedure Code Number(s)

N/A


Professional and outpatient claims with a date of service on or before September 30, 2015, must be billed using ICD-9 codes. Professional and outpatient claims with a date of service on or after October 1, 2015, must be billed using ICD-10 codes.

Facility/Institutional inpatient claims with a date of discharge on or before September 30, 2015, must be billed with ICD-9 codes. Facility/Institutional inpatient claims with a date of discharge on or after October 1, 2015, must be billed with ICD-10 codes.


ICD -10 Diagnosis Code Number(s)

D47.Z2 Castleman disease


HCPCS Level II Code Number(s)

J2860 Injection, siltuximab, 10 mg


Revenue Code Number(s)

N/A

Coding and Billing Requirements


Cross References




Policy History

Policy #MA08.006f
02/24/2020This policy was updated in accordance with US Food and Drug Administration (FDA) prescribing information and the National Comprehensive Cancer Network (NCCN) compendia.

Policy #MA08.006e
03/13/2019This policy has been reissued in accordance with the Company's annual review process.
06/06/2018This policy has been reissued in accordance with the Company's annual review process.
05/17/2017This policy has been updated with laboratory values consistent with the US Food and Drug Administration (FDA) labeling.

Policy #MA08.006d
10/01/2016This policy has been identified for the ICD-10 code update, effective 10/01/2016.

The following ICD-10 code has been added to this policy:
    D47.Z2 Castleman disease

The following ICD-10 codes have been deleted from this policy:
    R59.0 Localized enlarged lymph nodes
    R59.1 Generalized enlarged lymph nodes
    R59.9 Enlarged lymph nodes, unspecified

Policy #MA08.006c
05/18/2016This policy has been updated to reflect the medical necessity of siltuximab (Sylvant®) for the treatment of relapsed or refractory Unicentric Castleman’s Disease (UCD).

Policy #MA08.006b
01/01/2016This policy has been identified for the HCPCS code update, effective 01/01/2016.

The following HCPCS code has been added to this policy, as Medically Necessary:
    J2860 Injection, siltuximab, 10 mg

    The following HCPCS code has been termed from this policy:
    C9455 Injection, siltuximab, 10 mg

    The following HCPCS codes have been deleted from this policy:
    J3590

Policy #MA08.006a
07/01/2015This policy has been identified for the HCPCS code update, effective 07/01/2015.
The following HCPCS code has been added to this policy:
C9455 Injection, siltuximab, 10 mg

Policy #MA08.006
01/15/2015The following new policy has been developed to communicate the Company’s coverage criteria for siltuximab (Sylvant™).






Version Effective Date: 02/24/2020
Version Issued Date: 02/24/2020
Version Reissued Date: N/A