Contractor Name
HealthNow

Contractor Number
00801

Contractor Type
Carrier

LCD Database ID Number
L16510

LCD Title
Bortezomib (Velcade(TM)) for Injection

Contractor's Determination Number
DR025G04

AMA CPT / ADA CDT Copyright Statement
CPT codes, descriptions, and other data only are copyright 2006 American Medical Association (or such other data of publication of CPT). All Rights Reserved. Applicable FARS/DFARS clauses apply. Current Dental Terminology (CDT) (including procedure codes, nomenclature, descriptors and other data contained therein) is copyright by the American Dental Association. (C) 2002, 2004 American Dental Association. All rights reserved. Applicable FARS/DFARS apply.

CMS National Coverage Policy

   -   Title XVIII of the Social Security Act, Section 1862 (a)(7)

       This section excludes routine physical examinations.

   -   Title XVIII of the Social Security Act, Section 1862 (a)(1)(A)

       This section allows coverage and payment for only those services
       considered medically reasonable and necessary.

   -   Title XVIII of the Social Security Act, Section 1833 (e)

       This section prohibits Medicare payment for any claim that lacks the
       necessary information to process the claim.

Oversight Region
Region II

CMS Consortium
Northeast

Original Determination Effective Date
07/19/2004

Original Determination Ending Date

Revision Effective Date
04/27/2007

Revision Ending Date

Indications and Limitations of Coverage and/or Medical Necessity
Indications
FDA Labeled Indication
Bortezomib is indicated for the treatment of multiple myeloma patients who have received at least one prior therapy. Prior therapies may include: any prior steroids, e.g., dexamethasone, VAD; any prior alkylating agents, e.g., MP, VBMCP; any prior anthracyclines, e.g., VAD, mitoxantrone; any prior thalidomide therapy; any prior stem cell transplant/other high-dose therapy; prior experimental or other types of therapy. Disease progression may manifest as one or more of the following: unstable bone disease/fracture, increasing serum M-protein, increasing urinary excretion of light chains, worsening renal function, worsening anemia, increased frequency of infection, worsening hypercalcemia.

Effective 12/08/2006, the FDA approved Bortezomib for the treatment of patients withmantle cell lymphoma (MCL) who have received at least one prior therapy.

Off-Labeled Coverage:
For dates of service prior to 12/08/2006, based on supportive data, meeting the requirements of LCD "Off-Label Coverage of FDA-Approved Drugs" Bortezomib is covered for the treatment of mantle-cell lymphoma .

Effective 12/08/2006, based on supportive data, meeting the requirements of LCD "Off-Lable Coverage of FDA-Approved Drugs" Bortezomib is approved for first-line treatment for multiple myeloma.

Bortezomib is administered as bolus intravenous injection with recommended dosage of 1.3 mg/m2 twice weekly for two weeks (days 1, 4, 8 and 11), followed by a 10-day rest period (days 12-21). This 3-week period is considered a treatment cycle. Clinical studies shown patients to have received a maximum of 8 treatment cycles. At least 72 hours should elapse between consecutive doses of bortezomib.

Limitations
At this time, coverage of bortezomib is limited to the FDA-approved indications and the above listed off-label indications.

Coverage Topic
Prescription Drugs

Coding Information
Bill Type Codes:
Contractors may specify Bill Types to help providers identify those Bill Types typically used to report this service. Absence of a Bill Type does not guarantee that the policy does not apply to that Bill Type. Complete absence of all Bill Types indicates that coverage is not influenced by Bill Type and the policy should be assumed to apply equally to all claims.

Revenue Codes:
Contractors may specify Revenue Codes to help providers identify those Revenue Codes typically used to report this service. In most instances Revenue Codes are purely advisory; unless specified in the policy services reported under other Revenue Codes are equally subject to this coverage determination. Complete absence of all Revenue Codes indicates that coverage is not influenced by Revenue Code and the policy should be assumed to apply equally to all Revenue Codes.

    99999           Not Applicable

CPT/HCPCS Codes

    J9041           Injection, bortezomib, 0.1 mg

Does the CPT 30% Coding Rule Apply?
No

ICD-9 Codes that Support Medical Necessity
TRUNCATED DIAGNOSIS CODES ARE NOT ACCEPTABLE.

ICD-9-CM code listings may cover a range and include truncated codes. It is the provider's responsibility to avoid truncated codes by selecting a code(s) carried out to the highest level of specificity and selected from the ICD-9-CM book appropriate to the year in which the service was performed.

It is not enough to link the procedure code to a correct, payable ICD-9-CM code. The diagnosis or clinical signs/symptoms must be present for the procedure to be paid.

Further, these ICD-9CM codes can be used only with the conditions listed in the Indications and Limitations sections of the LCD.

    *202.20-202.28  Sezary's disease unspecified site ­ Sezary's disease
                    involving lymph nodes of multiple sites

    *202.30-202.38  Malignant histiocytosis unspecified site ­ Malignant
                    histiocytosis involving lymph nodes of multiple
                    sites

    *202.40-202.48  Leukemia reticuloedotheliosis unspecified site ­
                    Leukemic reticuloendotheliosis involving lymph nodes
                    of multiple sites

    *202.50-202.58  Letterer-Siwe disease unspecified site ­
                    Letterer-Siwe disease involving lymph nodes of
                    multiple sites

    *202.60-202.68  Malignant mast cell tumors unspecified site ­
                    Malignant mast cell tumors involving lymph nodes of
                    multiple sites

    *202.80-202.88  Other malignant lymphomas unspecified site ­ Other
                    malignant lymphomas involving lymph nodes of
                    multiple sites

    203.00          Multiple myeloma without remission

    V10.79          Personal history of other lymphatic and
                    hematopoietic neoplasms

ICD-9 Codes that DO NOT Support Medical Necessity
Use of any ICD-9-CM code not listed in the "ICD-9-CM Codes that Support Medical Necessity" section of this LCD will be denied.

Documentation Requirements

   1.  Each claim must be submitted with ICD-9-CM codes that reflect the
       condition of the patient, and indicate the reason(s) for which the
       service was performed. Claims submitted without ICD-9-CM codes will be
       returned.

   2.  Documentation in the medical record must support that bortezomib is
       administered for an indication specified in this policy.

   3.  Documentation must be available to Medicare upon request.

Sources of Information and Basis for Decision

   1.  Manufacturer's Package Insert for Bortezomib (Velcade(TM)) from
       Millennium Pharmaceuticals, Inc.

   2.  FDA approval letter for Bortezomib (Velcade(TM)), dated May 13, 2003.

   3.  Results from Velcade(TM) and Velcade A(TM) Studies. Millennium
       Pharmaceuticals:

       -    Phase I study of Velcade and thalidomide in patients with
            refractory disease

       -    Phase II clinical trial with Velcade (Bortezomib) for injection
            in patients with relapsed or refractory mantle cell lymphoma.
            Millennium Pharmaceuticals, July 2, 2003.

       -    Phase III APEX multicenter trial in relapsed and refractory
            myeloma

   4.  Yu C, Rahmani M, Conrad D, Subler M, Dent, P, Grant, S. The proteasome
       inhibitor bortezomib interacts synergistically with histone
       deacetylase inhibitors to induce apoptosis in Ber/Abl+ cells sensitive
       and resistant to ST1571. Blood, 2003 Aug 7 (Epub ahead of
       publication); Epub 2003 Jul 31.

   5.  HGSA Draft LMRP on Bortezomib, #I-55, presented to CAC 08/21/2003,
       with the following sources of information:

       -    Mack PC, Davies AM, Lara PN, Gumerlock PH, Gandara DR.,
            Integration of the proteasome inhibitor PS-341 (Velcade) into the
            therapeutic approach to lung cancer. Lung Cancer. 2003 Aug; 41
            Suppl 1:S89-96.

       -    Richardson PG, Barlogie B, Berenson J, Singhal S, Jagannath S,
            Irwin D, Rajkumar SV, Srkalovic G, Alsina M, Alexanian R, Siegel
            D, Orlowski RZ, Kuter D, Limentani SA, Lee S, Hideshima T,
            Esseltine DL, Kauffman M, Adams J, Schenkein DP, Anderson KC., A
            phase 2 study of bortezomib in relapsed, refractory myeloma. N
            Engl J Med. 2003 Jun 26;348(26):2609-17.

       -    Richardson P., Clinical update: proteasome inhibitors in
            hematologic malignancies. Cancer Treat Rev. 2003 May;29 Suppl
            1:33-9.

       -    Cusack JC. Rationale for the treatment of solid tumors with the
            proteasome inhibitor bortezomib.; Cancer Treat Rev. 2003 May;29
            Suppl 1:21-31.

       -    Adams J., The proteasome: structure, function, and role in the
            cell. Cancer Treat Rev. 2003 May;29 Suppl 1:3-9

       -    Kumar A, Loughran T, Alsina M, Durie BG, Djulbegovic B.,
            Management of multiple myeloma: a systematic review and critical
            appraisal of published studies. Lancet Oncol. 2003 May;
            4(5):293-304.

       -    Adams J., Potential for proteasome inhibition in the treatment of
            cancer. Drug Discov Today. 2003 Apr 1;8(7):307-15.

       -    Elliott PJ, Zollner TM, Boehncke WH., Proteasome inhibition: a
            new anti-inflammatory strategy.; J Mol Med. 2003
            Apr;81(4):235-45. Epub 2003 Mar 26.

       -    Orlowski RZ, Dees EC. The role of the ubiquitination-proteasome
            pathway in breast cancer: applying drugs that affect the
            ubiquitin-proteasome pathway to the therapy of breast cancer.;
            Breast Cancer Res. 2002;5(1):1-7. Epub 2002 Aug 14.

       -    Oyajobi BO, Mundy GR., Receptor activator of NF-kappaB ligand,
            macrophage inflammatory protein-1alpha, and the proteasome: novel
            therapeutic targets in myeloma.; Cancer. 2003 Feb 1; 97(3
            Suppl):813-7

       -    Orlowski RZ, Stinchcombe TE, Mitchell BS, Shea TC, Baldwin AS,
            Stahl S, Adams J, Esseltine DL, Elliott PJ, Pien CS, Guerciolini
            R, Anderson JK, Depcik-Smith ND, Bhagat R, Lehman MJ, Novick SC,
            O'Connor OA, Soignet SL., Phase I trial of the proteasome
            inhibitor PS-341 in patients with refractory hematologic
            malignancies. J Clin Oncol. 2002 Nov 15; 20(22):4420-7.

       -    Mitsiades N, Mitsiades CS, Richardson PG, Poulaki V, Tai YT,
            Chauhan D, Fanourakis G, Gu X, Bailey C, Joseph M, Libermann TA,
            Schlossman R, Munshi NC, Hideshima T, Anderson KC., The
            proteasome inhibitor PS-341 potentiates sensitivity of multiple
            myeloma cells to conventional chemotherapeutic agents:
            therapeutic applications. Blood. 2003 Mar 15; 101(6):2377-80.
            Epub 2002 Nov 07.

       -    Roodman GD., Role of the bone marrow microenvironment in multiple
            myeloma. J Bone Miner Res. 2002 Nov;17(11):1921-5.

   6.  Food and Drug Administration (FDA) approval letter NDA 21-602/S-006,
       March 25, 2005

   7.  Goy, Andre et al, "Phase II Study of Proteasome Inhibitor Bortezomib
       in Relapsed or Refractory B-Cell Non-Hodgkin's Lymphoma"

   8.  NCCN Practice Guidelines in Oncology-V.12005 Mantle Cell Lymphoma

   9.  Food and Drug Administration (FDA) approval letter NDA 21-602/S-010,
       December 8, 2006.

   1.  Goy, Andre, et al, Phase II Study of Proteasome Inhibitor Bortezomib
       in Relapsed or Refractory B-Cell Non-Hodgkin's Lymphoma. Journal of
       Clinical Oncology. 2005 February 1; 23(4):667-675.

   2.  Jagannath, Sundar, et al, Bortezomib therapy alone and in combination
       with dexamethasone for previously untreated symptomatic multiple
       myeloma. British Journal of Haematology. 129, 776-783. 2005 Blackwell
       Publishing Ltd.

   3.  Harousseau, Lean-Luc, et al, Bortezomib plus dexamethasone as
       induction treatment prior to autologous stem cell transplantation in
       patients with newly diagnosed multiple myeloma: results of an IFM
       phase II study. Haematologica/The Hematology Journal. 2006:
       91(11):1498-1505. 2006 Ferrata Storti Foundation.

   4.  Maetos, Maria-Victoria, et al, Bortezomib plus melphalan and
       prednisone in elderly untreated patients with multiple myeloma:
       results of a multicenter phase ½ study. Blood. 2006 October 1;
       108(7):2165-2172.

   5.  NCCN Clinical Practice Guidelines in Oncology-V.3.2007 Multiple
       Myeloma

   6.  Oakervee, Heather, E., et al, PAD combination therapy
       (PS-341/bortezomib, doxorubicin and dexamethasone) for previously
       untreated patients with multiple myeloma. British Journal of
       Haematology. 129, 755-762. 2005 Blackwell Publishing Ltd.

   7.  O'Connor, Owen A., et al, Phase II Clinical Experience With the Novel
       Proteasome Inhibitor Bortezomib in Patients With Indolent
       Non-Hodgkin's Lymphoma and Mantle Cell Lymphoma. Journal of Clinical
       Oncology. 2005 February 1; 23(4): 676-684.

   -   This LCD was presented at the October 8, 2003, Carrier Advisory
       Committee meeting by Group Health Incorporated.

   -   This LCD does not reflect the sole opinion of the contractor or
       Contractor Medical Director. Although the final decision rests with
       the carrier, this LCD was developed in cooperation with advisory
       groups, which includes representatives from Hematology and Oncology
       and the Medical Societies of the States of New York and New Jersey.

End Date of Comment Period
11/21/2003

Start Date of Notice Period
07/13/2007

Revision History Number
4

Revision History Explanation
Revision #4: This LCD is revised to include FDA approval for Bortezomib for the treatment of patients with mantle cell lymphoma (MCL) who have received at least one prior therapy effective 12/08/2006 and off-labeled indication for first-line treatment for multiple myeloma effective 12/08/2006. Removed drug administration codes from the CPT/HCPCS code section.

Revision #3: Added ICD-9-CM code V10.79. Revised descriptions of ICD-9 CM code ranges. Revised the "FDA Labeled Indication" to indicate that effective 03/25/2005, the second part of the first sentence ("_and have demonstrated disease progression on the last therapy.") was removed. Revised last sentence under Limitations section.

Revision #2: Revised indications to require one prior therapy instead of two, added coverage topic, and ICD-9-CM range 202.20-202.28.

Correction: 12/07/05 ­ Diagnosis code range 202.00-202.28 was corrected to 202.20-202.28. LCD number was not changed.

Revision #1: Added new HCPCS codes J9041, G0357, and G0358 for 2005. Indications section was updated effective 03/25/2005 to require one prior therapy instead of two. Revised the indications section to include off-label coverage for mantle-cell lymphoma. Additional ICD-9-CM codes 202.20-202.88 were added covered from 01/01/2005. Removed Contractor Determination Number. Updated Sources of Information.

Does this LCD contain a "Least Costly Alternative" provision?
No