Notification



Notification Issue Date:



Medicare Advantage Policy

Title:Bortezomib (Bortezomib for Injection, Velcade®)
Policy #:MA08.037f

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

Bortezomib for Injection (intravenous) and bortezomib (Velcade®) intravenous or subcutaneous injection are considered medically necessary and, therefore, covered for any of the following indications:

CASTLEMAN'S DISEASE (CD)
  • Subsequent therapy with or without rituximab for multicentric CD that has progressed following treatment of relapsed/refractory or progressive disease

MANTLE CELL LYMPHOMA
  • For the treatment of individuals with untreated or relapsed mantle cell lymphoma (bortezomib [Velcade®])
  • For the treatment of individuals with relapsed mantle cell lymphoma who have received at least one prior therapy (bortezomib [Bortezomib for Injection])
  • Induction therapy for stage I-II disease (localized presentation, extremely rare) as initial therapy (an National Comprehensive Cancer Network [NCCN-preferred] regimen), or for partial response, progression, or relapse after treatment with involved site radiation therapy alone, or for aggressive stage II bulky, III, or IV disease or symptomatic indolent stage II bulky, III, or IV disease in patients who are not candidates for high-dose therapy/autologous stem cell rescue as a component of less aggressive therapy with VR-CAP (bortezomib, rituximab, cyclophosphamide, doxorubicin, and prednisone) regimen
  • Second-line therapy for stage I-II disease, aggressive stage II bulky, III, or IV disease, or symptomatic indolent stage II bulky, III, or IV disease to achieve complete response after partial response to induction therapy, or for relapsed or progressive disease following an extended response duration to prior chemoimmunotherapy (> expected median progression free survival)
    • as a single agent (NCCN-preferred regimen)
    • in combination with rituximab (NCCN-preferred regimen)

MULTIPLE MYELOMA
  • For the treatment of individuals with untreated or relapsed multiple myeloma
  • For the treatment of individuals with newly diagnosed multiple myeloma who are ineligible for autologous stem cell transplant, in combination with daratumumab, melphalan, and prednisone
  • Primary chemotherapy for active (symptomatic) myeloma or for disease relapse after 6 months following primary induction therapy with the same regimen
    • in combination with:
      • dexamethasone
      • dexamethsaone and lenalidomide (NCCN-preferred)
      • dexamethasone and cyclophosphamide (NCCN-preferred as initial treatment in those with acute renal insufficiency)
      • dexamethasone and doxorubicin or thalidomide for transplant candidates
    • in VTD-PACE (bortezomib, thalidomide, dexamethasone, cisplatin, doxorubicin, cyclophosphamide and etoposide) regimen for transplant candidates
  • Maintenance therapy as a single agent:
    • for active (symptomatic) myeloma responding to primary myeloma therapy
    • for stable or responsive disease following autologous stem cell transplant
  • Therapy for previously treated myeloma for disease relapse or for progressive disease:
    • in combination with dexamethasone and lenalidomide (NCCN-preferred)
    • in combination with dexamethasone and daratumumab (NCCN-preferred)
    • in combination with dexamethasone and bendamustine
    • in combination with dexamethasone and cyclophosphamide
    • in combination with dexamethasone
    • in combination with dexamethasone and liposomal doxorubicin
    • in combination with elotuzumab and dexamethasone
    • in combination with pomalidomide and dexamethasone for individuals who have received at least two prior therapies, including an immunomodulatory agent and a proteasome inhibitor, and have demonstrated disease progression on or within 60 days of completion of last therapy
    • in VTD-PACE (bortezomib, dexamethasone, thalidomide, cisplatin, doxorubicin, cyclophosphamide, and etoposide) regimen
    • in combination with panobinostat and dexamethasone for individuals who have received at least 2 prior regimens, including bortezomib and an immunomodulatory agent

SYSTEMIC LIGHT-CHAIN AMYLOIDOSIS
  • Treatment for newly diagnosed disease or for relapsed/refractory disease as a repeat of initial therapy if relapse-free for several years
    • In combination with cyclophosphamide and dexamethasone, as NCCN-preferred therapy
    • As a single agent or in combination with dexamethasone with or without melphalan
  • Treatment for relapsed/refractory disease as a single agent or in combination with dexamethasone with or without melphalan

T-CELL LEUKEMIA/LYMPHOMA, ADULT
  • Second-line therapy (with intention to proceed to high-dose therapy/allogeneic stem cell rescue) or subsequent therapy to HDT/ASCR as a single agent for nonresponders to first-line therapy for acute or lymphoma subtypes

WALDENSTROM'S MACROGLOBULINEMIA/LYMPHOPLASMACYTIC LYMPHOMA
  • Single-agent therapy, in combination with dexamethasone, or in combination with rituximab with or without dexamethasone as:
    • primary therapy
    • therapy for previously treated disease that does not respond to primary therapy
    • for progressive or relapsed disease

EXPERIMENTAL/INVESTIGATIONAL

All other uses of bortezomib (Bortezomib for Injection, Velcade®) are considered experimental/investigational and, therefore, not covered unless the indication is supported as an accepted off-label use, as defined in the 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 this service; therefore, the Company policy is applicable.

Bortezomib (Bortezomib for Injection, Velcade®) is 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 bortezomib (Bortezomib for Injection, Velcade®) is covered under a member's medical benefit (Part B benefit). It does not address instances when bortezomib (Bortezomib for Injection, Velcade®) is covered under a member’s pharmacy benefit (Part D benefit).

BENEFIT APPLICATION

Subject to the terms and conditions of the applicable Evidence of Coverage, bortezomib (Bortezomib for Injection, Velcade®) 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

Bortezomib (Velcade®) was approved by the FDA on May 2003 for use in the treatment of individuals with multiple myeloma. In December 2006, bortezomib (Velcade®) was approved by the FDA for the use in the treatment of individuals with mantle cell lymphoma. Supplemental approvals for bortezomib (Velcade®) have since been issued by the FDA.

Bortezomib for Injection was approved by the FDA on November 06, 2017 for intravenous use in the treatment of individuals with multiple myeloma and for use in the treatment of individuals with mantle cell lymphoma who have received at least 1 prior therapy.

PEDIATRIC USE

The safety and effectiveness of bortezomib (Velcade®) and Bortezomib for Injection in children have not been established.

Description

Bortezomib (Bortezomib for Injection, Velcade®) is a proteasome inhibitor, which is used for targeted antineoplastic therapy. The proteasome is an enzyme complex that is found in all biological cells. It is involved in degrading proteins that control the cell cycle and in cellular processes that maintain cell homeostasis. By blocking the proteasome, bortezomib (Bortezomib for Injection, Velcade®) disrupts numerous biologic pathways, including those related to the growth and survival of cancer cells. Bortezomib (Bortezomib for Injection, Velcade®) has demonstrated the ability to delay tumor growth in vivo in several tumor models, including multiple myeloma.

In May 2003, bortezomib (Velcade®) was approved by the US Food and Drug Administration (FDA) as an orphan drug (a drug used to treat, prevent, or diagnose a rare disease) under the accelerated approval program for use in the treatment of individuals with multiple myeloma. In May 2007, the FDA approved bortezomib (Velcade®) plus doxorubicin HCl liposome injection (Doxil®) combination for the treatment of individuals with multiple myeloma who had previously not taken bortezomib (Velcade®) and who have received at least one prior therapy. In June 2008, the FDA granted supplemental approval for bortezomib (Velcade®) that removed the prior therapy requirement for individuals with multiple myeloma.

In December 2006, the FDA approved the use of bortezomib (Velcade®) in the treatment of individuals with mantle cell lymphoma (a form of non-Hodgkin's lymphoma affecting the B-lymphocytes) who have received at least one prior therapy. In October 2014, the FDA removed the at least one prior therapy requirement for individuals with mantle cell lymphoma.

On January 23, 2012, based on results from a randomized Phase 3 non-inferiority trial, the FDA granted a supplemental approval for bortezomib (Velcade®) for subcutaneous route of administration for treatment of individuals with multiple myeloma and for treatment of individuals with mantle cell lymphoma who have received at least one prior therapy. In general, the overall response rate and complete response rates of bortezomib (Velcade®) administered subcutaneously or intravenously achieved similar efficacy regardless of how bortezomib (Velcade®) was administered. However, differences were observed in the incidence of peripheral neuropathy experienced in the trial. In the subcutaneous arm of the study, six percent of individuals experienced Grade 3 (i.e., severe symptoms; limiting self care activities of daily living) or higher peripheral neuropathy, compared to 16 percent in the intravenous arm of the study.

On November 06, 2017, bortezomib (Bortezomib for Injection) was approved by the FDA for the intravenous use in the treatment of individuals with multiple myeloma and in the treatment of individuals with mantle cell lymphoma who have received at least 1 prior therapy. Bortezomib (Bortezomib for Injection) was approved through the 505(b)(2) NDA pathway process. This product is formulated with boric acid or glycine, while bortezomib (Velcade®) contains mannitol.

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

Bortezomib (Velcade®). American Hospital Formulary Service (AHFS). AHFS Drug Information 2018. [Lexicomp Online Web site]. 09/14/2018. Available at: http://online.lexi.com/lco/action/home [via subscription only]. Accessed February 21, 2019.

Bortezomib (Velcade®). Elsevier Clinical Pharmacology Compendium. Indications/dosage [Clinical Key Web site]. 08/17/2018. Available at: https://www.clinicalkey.com/pharmacology/monograph/2794?sec=monindi&n=Velcade [via subscription only]. Accessed February 21, 2019.

Bortezomib (Velcade®). Lexi-Drugs Compendium. [Lexicomp Online Web site]. 02/16/2019. Available at: http://online.lexi.com/lco/action/home [via subscription only]. Accessed February 21, 2019.

Bortezomib (Velcade®). Micromedex® 2.0 Healthcare Series. DrugDex® [Micromedex® Web site]. 2019. Available at: http://www.micromedexsolutions.com/micromedex2/librarian [via subscription only]. Accessed February 21, 2019.

Moreau P, Pylypenko H, Grosicki S, et. al. Subcutaneous versus intravenous administration of bortezomib in patients with relapsed multiple myeloma: a randomized, phase 3, non-inferiority study. Lancet Oncol. 2011;12:431-40.

National Comprehensive Cancer Network (NCCN). NCCN Clinical Practice Guidelines in Oncology - B-cell Lymphomas V1.2019. [NCCN Web site]. 11/30/2018. Available at: https://www.nccn.org/professionals/physician_gls/pdf/b-cell.pdf [via subscription only]. Accessed February 21, 2019.

National Comprehensive Cancer Network (NCCN). NCCN Clinical Practice Guidelines in Oncology - Multiple Myeloma V2.2019. [NCCN Web site]. 11/16/2018. Available at: https://www.nccn.org/professionals/physician_gls/pdf/myeloma.pdf [via subscription only]. Accessed February 21, 2019.

National Comprehensive Cancer Network (NCCN). NCCN Clinical Practice Guidelines in Oncology - Systemic Light Chain Amyloidosis V1.2019. [NCCN Web site]. 10/26/2018. Available at: https://www.nccn.org/professionals/physician_gls/pdf/amyloidosis.pdf [via subscription only]. Accessed February 21, 2019.

National Comprehensive Cancer Network (NCCN). NCCN Clinical Practice Guidelines in Oncology - T-Cell Lymphomas V2.2019. [NCCN Web site]. 12/12/2018. Available at: https://www.nccn.org/professionals/physician_gls/pdf/t-cell.pdf [via subscription only]. Accessed February 21, 2019.

National Comprehensive Cancer Network (NCCN). NCCN Clinical Practice Guidelines in Oncology - Waldenstrom's Macroglobulinemia/Lymphoplasmacytic Lymphoma. V2.2019. [NCCN Web site]. 09/14/2018. Available at: http://www.nccn.org/professionals/physician_gls/pdf/waldenstroms.pdf [via subscription only]. Accessed February 21, 2019.

National Comprehensive Cancer Network (NCCN). NCCN Drugs & Biologics Compendium™. Bortezomib. [NCCN Web site]. 2019. Available at: http://www.nccn.org/professionals/drug_compendium/content/contents.asp [via subscription only]. Accessed February 21, 2019.

US Food and Drug Administration (FDA). Center for Drug Evaluation and Research. Bortezomib (Velcade®). Supplemental approval letter. [FDA Web site]. 05/13/2003. Available at: http://www.accessdata.fda.gov/drugsatfda_docs/appletter/2003/21602ltr.pdf. Accessed February 21, 2019.

US Food and Drug Administration (FDA). Center for Drug Evaluation and Research. Bortezomib (Bortezomib for Injection) prescribing information and approval letter. [FDA Web site]. 06/2017. Available at:
https://www.accessdata.fda.gov/drugsatfda_docs/label/2017/205004s000lbl.pdf . Accessed February 21, 2019.

US Food and Drug Administration (FDA). Center for Drug Evaluation and Research. Bortezomib (Velcade®) prescribing information and approval letter. [FDA Web site]. 06/2017. Available at: https://www.accessdata.fda.gov/drugsatfda_docs/label/2017/021602s043lbl.pdf. Accessed February 21, 2019.

US Food and Drug Administration (FDA). Center for Drug Evaluation and Research. daratumumab (Darzalex) prescribing information and approval letter. [FDA Web site]. 05/07/2018. Available at: https://www.accessdata.fda.gov/drugsatfda_docs/label/2018/761036s013lbl.pdf . Accessed February 21, 2019.



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)

C83.00 Small cell B-cell lymphoma, unspecified site

C83.01 Small cell B-cell lymphoma, lymph nodes of head, face, and neck

C83.02 Small cell B-cell lymphoma, intrathoracic lymph nodes

C83.03 Small cell B-cell lymphoma, intra-abdominal lymph nodes

C83.04 Small cell B-cell lymphoma, lymph nodes of axilla and upper limb

C83.05 Small cell B-cell lymphoma, lymph nodes of inguinal region and lower limb

C83.06 Small cell B-cell lymphoma, intrapelvic lymph nodes

C83.07 Small cell B-cell lymphoma, spleen

C83.08 Small cell B-cell lymphoma, lymph nodes of multiple sites

C83.09 Small cell B-cell lymphoma, extranodal and solid organ sites

C83.10 Mantle cell lymphoma, unspecified site

C83.11 Mantle cell lymphoma, lymph nodes of head, face, and neck

C83.12 Mantle cell lymphoma, intrathoracic lymph nodes

C83.13 Mantle cell lymphoma, intra-abdominal lymph nodes

C83.14 Mantle cell lymphoma, lymph nodes of axilla and upper limb

C83.15 Mantle cell lymphoma, lymph nodes of inguinal region and lower limb

C83.16 Mantle cell lymphoma, intrapelvic lymph nodes

C83.17 Mantle cell lymphoma, spleen

C83.18 Mantle cell lymphoma, lymph nodes of multiple sites

C83.19 Mantle cell lymphoma, extranodal and solid organ sites

C88.0 Waldenström macroglobulinemia

C90.00 Multiple myeloma not having achieved remission

C90.01 Multiple myeloma in remission

C90.02 Multiple myeloma in relapse

C90.10 Plasma cell leukemia not having achieved remission

C90.11 Plasma cell leukemia in remission

C90.12 Plasma cell leukemia in relapse

C91.50 Adult T-cell lymphoma/leukemia (HTLV-1-associated) not having achieved remission

C91.52 Adult T-cell lymphoma/leukemia (HTLV-1-associated), in relapse

D47.Z2 Castleman disease

E85.81 Light chain (AL) amyloidosis




HCPCS Level II Code Number(s)



J9041 Injection, bortezomib (velcade), 0.1 mg

J9044 Injection, bortezomib, not otherwise specified, 0.1 mg



Revenue Code Number(s)

N/A

Coding and Billing Requirements

    BILLING REQUIREMENTS

    If there is no specific HCPCS code available for the drug administered, then the drug must be reported with the most appropriate unlisted code along with the corresponding National Drug Code (NDC).

Cross References




Policy History

Revisions from Policy MA08.037f
04/15/2019This version of the policy will become effective 04/15/2019.

The following criterion has been deleted from this policy:

PRIMARY CUTANEOUS CD30+ T-CELL LYMPHOPROLIFERATIVE DISORDERS as indication for bortezomib (bortezomib for injection, Velcade®)

The following ICD-10 CM code has been removed from this policy:

C86.6 Primary cutaneous CD30-positive T-cell proliferations

Revisions from Policy MA08.037e
01/01/2019This policy has been identified for the HCPCS code update, effective 01/01/2019.

The following HCPCS code has been termed from this policy:
J3490 Unclassified drugs

The following HCPCS code has been added to this policy:
J9044 Injection, bortezomib, not otherwise specified, 0.1 mg

The following HCPCS code has revised narrative in this policy:
FROM: J9041 Injection, bortezomib, 0.1 mg
TO: J9041 Injection, bortezomib (velcade), 0.1 mg

MA08.037d
07/09/2018This policy has undergone a routine review, and the medical necessity criteria have been revised as follows:

This policy has been updated in consideration of revisions within the US Food and Drug Administration (FDA) labeling and National Comprehensive Cancer Network (NCCN) compendia for Velcade®, and another recently approved product, Bortezomib for Injection.

MA08.037c
10/01/2017This policy has been identified for the HCPCS code update, effective 10/01/2017.

The following HCPCS codes have been added to this policy:
E85.81 Light chain (AL) amyloidosis

The following HCPCS codes have been removed from this policy:
E85.8 Other amyloidosis

MA08.037b
10/01/2016This version of the policy will become effective 10/01/2016.

This policy has been updated to be consistent with the US Food and Drug Administration (FDA) labeling and Compendia. The policy criteria for Bortezomib (Velcade®) was updated to include additional criteria for individuals with mantle cell lymphoma.

The following code was added to the policy: D47.Z2, E85.8.
The following code was removed from the policy:E85.9, R59.0, R59.1, R59.9.

MA08.037a
01/05/2016This policy was updated to be consistent with US Food and Drug Administration (FDA) Labeling and Drug Compendia. Additional criteria for multiple myeloma and mantle cell for intravenous (IV) bortezomib (Velcade®)have been added to the policy. Castleman's disease has been added as a new indication for IV bortezomib (Velcade®). Peripheral T-cell Lymphomas for IV bortezomib (Velcade®) have been removed from the policy. Additional criteria for multiple myeloma has been added to the policy for subcutaneous (SQ) bortezomib (Velcade®). Mantle cell lymphoma has been removed for SQ bortezomib (Velcade®). Bortezomib (Velcade®) will only be covered for indications included in this policy or indications that meets the criteria of the Off-label Coverage for Prescription Drugs and Biologics policy.

The following ICD-10 codes were added to the policy: R59.0, R59.1, R59.9

The following ICD-10 codes were removed from the policy: 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, C86.2, C86.4, C86.5, C86.6

MA08.037
01/01/2015This is a new policy. This policy was posted for notification on 10/01/2014. On 10/03/2014, the policy was updated and contains the following modifications:

For intravenous bortezomib (Velcade®), the criteria has been revised for the following:
  • Multiple myeloma
  • Systemic light-chain amyloidosis
  • Mantle cell lymphoma
  • Adult T-cell leukemia/lymphoma
  • Waldenstrom's Macroglobulinemia/Lymphoplasmacytic Lymphoma

The following indications for intravenous bortezomib (Velcade®) were added:
  • Primary cutaneous CD30+ T-cell lymphoproliferative disorders
  • Other peripheral T-cell Lymphomas

The criteria for subcutaneous bortezomib (Velcade®) were revised for the following:
  • Multiple myeloma
  • Mantle cell lymphoma

The following ICD-9 diagnosis codes were added to the policy: 203.10, 203.12, 202.80, 202.81, 202.82.






Version Effective Date: 04/15/2019
Version Issued Date: 04/15/2019
Version Reissued Date: N/A