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This medical policy (medical coverage guideline) is Copyright 2017, Blue Cross and Blue Shield of Florida (BCBSF). All Rights Reserved. You may not copy or use this document or disclose its contents without the express written permission of BCBSF. The medical codes referenced in this document may be proprietary and owned by others. BCBSF makes no claim of ownership of such codes. Our use of such codes in this document is for explanation and guidance and should not be construed as a license for their use by you. Before utilizing the codes, please be sure that to the extent required, you have secured any appropriate licenses for such use. Current Procedural Terminology (CPT) is copyright 2017 American Medical Association. All Rights Reserved. No fee schedules, basic units, relative values, or related listings are included in CPT. The AMA assumes no liability for the data contained herein. Applicable FARS/DFARS restrictions apply to government use. CPT® is a trademark of the American Medical Association. The use of specific product names is illustrative only. It is not intended to be a recommendation of one product over another, and is not intended to represent a complete listing of all products available.

09-J2000-40

Original Effective Date: 06/15/14

Reviewed: 05/11/16

Revised: 02/15/17

Subject: Bendamustine HCl (Bendeka®, Treanda®) Injection

THIS MEDICAL COVERAGE GUIDELINE IS NOT AN AUTHORIZATION, CERTIFICATION, EXPLANATION OF BENEFITS, OR A GUARANTEE OF PAYMENT, NOR DOES IT SUBSTITUTE FOR OR CONSTITUTE MEDICAL ADVICE. ALL MEDICAL DECISIONS ARE SOLELY THE RESPONSIBILITY OF THE PATIENT AND PHYSICIAN. BENEFITS ARE DETERMINED BY THE GROUP CONTRACT, MEMBER BENEFIT BOOKLET, AND/OR INDIVIDUAL SUBSCRIBER CERTIFICATE IN EFFECT AT THE TIME SERVICES WERE RENDERED. THIS MEDICAL COVERAGE GUIDELINE APPLIES TO ALL LINES OF BUSINESS UNLESS OTHERWISE NOTED IN THE PROGRAM EXCEPTIONS SECTION.

           
Dosage/ Administration Position Statement Billing/Coding Reimbursement Program Exceptions Definitions
           
Related Guidelines Other References Updates  
           

DESCRIPTION:

Bendamustine (Bendeka®, Treanda®) is an alkylating agent; similar to other alkylating agents (e.g., cisplatin), it exerts its antineoplastic activity by cross-linking DNA and ultimately resulting in DNA single-strand and double-strand breaks. Bendamustine was originally developed in 1963 and has been used in Germany since 1971; however, Treanda was not approved by the US Food and Drug Administration (FDA) until March 2008. In December 2015, a new formulation of bendamustine, Bendeka®, was approved by the FDA. Compared to Treanda, Bendeka has the advantages of allowing for a lower infusion volume (50 mL vs. 500 mL) and a faster infusion time (10 minutes vs. 30 to 60 minutes). Bendeka contains different solubilizes including monothioglycerol, and polyethylene glycol 400. Currently, bendamustine is FDA-approved for the treatment of chronic lymphocytic leukemia (CLL) and non-Hodgkin’s lymphoma (NHL). In addition to these FDA-approved indications, use in the treatment of a variety of other oncologic indications is supported by standard reference compendia (e.g., National Comprehensive Cancer Network [NCCN]). Bendamustine was granted orphan designation by the FDA for the treatment of CLL in 2007 and for the treatment of indolent B-cell NHLs in 2013.

POSITION STATEMENT:

Initiation of bendamustine meets the definition of medical necessity when used for the treatment of ANY of the following indications AND the dose does not exceed a total of 240 mg/m2 per 21-day treatment cycle:

1. Classical Hodgkin’s lymphoma when used as a single agent and EITHER of the following:

a. Bendamustine will be used as second-line or later therapy for relapsed or refractory disease

b. Bendamustine will be used as palliative therapy in members over the age of 60 years

2. Previously-treated relapsed, refractory, or progressive multiple myeloma (MM) when bendamustine will be used as a single agent, or in combination with BOTH lenalidomide (Revlimid) and dexamethasone

3. Waldenström’s macroglobulinemia (a.k.a., lymphoplasmacytic lymphoma) when bendamustine will be used as primary therapy, or as treatment for progressive or relapsed disease

4. Non-Hodgkin’s lymphoma when used for ANY of the following types and ALL associated criteria are met:

a. Adult T-Cell leukemia/lymphoma (ATLL) when bendamustine is being used for non-responders to first-line therapy for acute disease or lymphoma (NOT to be used for chronic/smoldering ATLL)

b. AIDS-related B-cell lymphoma when bendamustine will be used as second-line or later therapy as a single agent or in combination with rituximab for relapsed disease AND the member is a non-candidate for high-dose therapy

c. Chronic lymphocytic leukemia (CLL) when bendamustine will be used as a single agent or in combination with rituximab AND the member does NOT have the del(17p) mutation

d. Diffuse large B-cell lymphoma when bendamustine will be used as second-line or later therapy as a single agent or in combination with rituximab AND the member is a non-candidate for high-dose therapy

e. Follicular Lymphoma when bendamustine will be used as EITHER:

i. First-line therapy in combination with rituximab

ii. Second-line or subsequent therapy as a single agent, or in combination with either rituximab or obinutuzumab (Gazyva®) for refractory or progressive disease

f. Gastric MALT Lymphoma when bendamustine will be used as EITHER:

i. First-line therapy for stage IV disease (i.e., T1-4 N3 M0, or T1 N0-3 M1) in combination with rituximab

ii. Second-line or later therapy for recurrent or progressive disease as a single agent, or in combination with either rituximab or obinutuzumab

g. Mantle Cell Lymphoma when bendamustine will be used as EITHER:

i. Less aggressive induction therapy in combination with rituximab

ii. Second-line therapy with or without rituximab for relapsed, refractory, or progressive disease

h. Mycosis Fungoides (MF)/Sezary Syndrome (SS) when bendamustine will be used as single-agent therapy for ANY of the following:

i. Stage IB to IIA disease with histologic evidence of folliculotropic or large cell transformation

ii. Stage IIB with generalized extent tumor, transformed, and/or folliculotropic disease with or without skin-directed therapy

iii. Stage IV non-Sezary or visceral disease

i. Non-gastric MALT lymphoma when bendamustine will be used as EITHER:

i. First-line therapy for stage IV disease in combination with rituximab

ii. Second-line or later therapy for recurrent or progressive disease as a single agent, or in combination with either rituximab or obinutuzumab

j. Peripheral T-cell Lymphoma when bendamustine will be used as second-line or subsequent therapy for ANY of the following relapsed or refractory types of disease:

i. Angioimmunoblastic T-cell lymphoma

ii. Peripheral T-cell lymphoma not otherwise specified (NOS)

iii. Anaplastic large cell lymphoma (ALCL)

iv. Enteropathy-associated T-cell lymphoma

k. Primary cutaneous B-cell lymphoma when bendamustine will be used for treatment of ANY of the following types:

i. Primary cutaneous marginal zone or follicle center lymphoma and ANY of the following:

1. First-line therapy for newly diagnosed generalized extracutaneous disease in combination with rituximab

2. Second-line therapy for refractory generalized cutaneous disease as a single agent or in combination with either rituximab or obinutuzumab

3. Second-line or later therapy for relapsed generalized extracutaneous disease as a single agent or in combination with either rituximab or obinutuzumab

ii. Second-line or subsequent therapy with or without either rituximab or obinutuzumab for relapsed or refractory primary cutaneous diffuse large B-cell lymphoma, leg type AND the member is a non-candidate for high-dose therapy

l. Primary cutaneous CD30+ T-Cell lymphoproliferative disorders when bendamustine will be used as a single agent for EITHER:

i. Relapsed or refractory primary cutaneous anaplastic large cell lymphoma (ALCL) with multifocal lesions

ii. Relapsed or refractory cutaneous ALCL with regional nodes (excludes systemic ALCL)

m. Splenic Marginal Zone Lymphoma when bendamustine will be used as EITHER:

i. First-line medical therapy in combination with rituximab for disease progression following splenectomy

ii. Second-line or later medical therapy for progressive or refractory disease as a single agent, or in combination with either rituximab or obinutuzumab

Approval duration: 180 days

Continuation of bendamustine meets the definition of medical necessity when ALL of the following criteria are met:

1. An authorization/reauthorization for bendamustine has been previously approved by Florida Blue or another health plan in the past 2 years for a Florida Blue-approved indication, OR the member previously met ALL indication-specific initiation criteria

2. Member’s disease has not progressed during treatment with bendamustine.

3. The dose of bendamustine does not exceed a total of 240 mg/m2 per 21-day treatment cycle.

Approval duration: 1 year

DOSAGE/ADMINISTRATION:

THIS INFORMATION IS PROVIDED FOR INFORMATIONAL PURPOSES ONLY AND SHOULD NOT BE USED AS A SOURCE FOR MAKING PRESCRIBING OR OTHER MEDICAL DETERMINATIONS. PROVIDERS SHOULD REFER TO THE MANUFACTURER’S FULL PRESCRIBING INFORMATION FOR DOSAGE GUIDELINES AND OTHER INFORMATION RELATED TO THIS MEDICATION BEFORE MAKING ANY CLINICAL DECISIONS REGARDING ITS USAGE.

FDA-approved: bendamustine is indicated for the treatment of CLL, and indolent B-Cell NHL that has progressed during or within six months of treatment with rituximab or a rituximab-containing regimen. The recommended dosing for bendamustine is based on indication and is described in Table 2.

Table 2: Approved Dosing and Administration

Indication

Dosing/Administration

Dose Modifications

CLL

100 mg/m2 IV over 30 minutes (for Treanda) or 10 minutes (for Bendeka) on days 1 and 2 of a 28 day cycle, up to 6 cycles

1. Hematologic toxicity

a. Grade 3 or greater: reduce to 50 mg/m2 on days 1 and 2 of each cycle

b. Recurrence of grade 3 or greater: reduce to 25 mg/m2 on days 1 and 2 of each cycle

2. Non-hematologic toxicity: clinically significant Grade 3 or greater, reduce to 50 mg/m2 on days 1 and 2 of each cycle

3. Dose re-escalation may be considered

NHL

120 mg/m2 IV over 60 minutes (for Treanda) or 10 minutes (for Bendeka) on days 1 and 2 of a 21 day cycle, up to 8 cycles

1. Hematologic toxicity

a. Grade 4: reduce the dose to 90 mg/m2 on days 1 and 2 of each cycle

b. Recurrence of grade 4: reduce dose to 60 mg/m2 on days 1 and 2 of each cycle

2. Non-hematologic toxicity

a. Grade 3 or greater: reduce the dose to 90 mg/m2 on days 1 and 2 of each cycle

b. Recurrence of grade 3 or greater: reduce dose to 60 mg/m2 on days 1 and 2 of each cycle

CLL, chronic lymphocytic leukemia; NHL, non-Hodgkin lymphoma; IV, intravenous

General dosing considerations: delay treatment for Grade 4 hematologic toxicity or clinical significant grade 2 or greater non-hematologic toxicity.

Renal impairment: Do not use if CRC is < 40 mL/min. Use with caution in lesser degrees of renal impairment.

Hepatic impairment: Do not use in moderate or severe hepatic impairment (Child-Pugh Category B or C). Use with caution in mild hepatic impairment.

Do NOT use bendamustine injection with devices that contain polycarbonate or acrylonitrile-butadiene-styrene (ABS), including most Closed System Transfer Devices (CSTDs).

Product Availability:

Treanda - 25 or 100 mg lyophilized powder in single-use vials that must be reconstituted prior to infusion, and 45 mg/0.5 mL and 180 mg/2 mL solution in single-use vials (90 mg/mL). The solutions must be stored refrigerated between 2°- 8°C (36°- 46°F) and protected from light. The powder may be stored up to 25°C (77°F) with excursions permitted up to 30°C (86°F) and protected from light.

Bendeka - 100 mg/4 mL solution in multiple-dose vials (25 mg/mL). Store refrigerated between 2°- 8°C (36°- 46°F) and protect from light

PRECAUTIONS:

Contraindication:

Prior history of hypersensitivity reactions to bendamustine (both Treanda and Bendeka), or polyethylene glycol 400, propylene glycol, or monothioglycerol (Bendeka only)

Warnings:

1. Myelosuppression:  Delay or reduce dose. Restart treatment based on ANC and platelet count recovery. Complications of myelosuppression may lead to death.

2. Infections:  Monitor for fever and other signs of infection and treat promptly.

3. Anaphylaxis and Infusion Reactions: Severe and anaphylactic reactions have occurred; monitor clinically and discontinue bendamustine. Pre-medicate in subsequent cycles for milder reactions.

4. Tumor Lysis Syndrome:  Acute renal failure and death; anticipate and use supportive measures.

5. Skin Reactions:  Discontinue for severe skin reactions. Cases of SJS and TEN, some fatal, have been reported when bendamustine was administered concomitantly with allopurinol and other medications known to cause these syndromes.

6. Other Malignancies: Pre-malignant and malignant diseases have been reported.

7. Extravasation: Assure good venous access and monitor infusion site during and after administration.

8. Embryo-fetal toxicity: Fetal harm can occur when administered to a pregnant woman. Women should be advised to avoid becoming pregnant when receiving bendamustine.

9. Drug Interactions: Concomitant CYP1A2 inducers or inhibitors have the potential to affect the exposure of bendamustine.

BILLING/CODING INFORMATION:

The following codes may be used to describe:

HCPCS Coding (Treanda®)

J9033

Injection, bendamustine HCl (Treanda), 1 mg

HCPCS Coding (Bendeka®)

J9034

Injection, bendamustine HCl (Bendeka), 1 mg

ICD-10 Diagnoses Codes That Support Medical Necessity: (Effective 10/01/15)

B20 w/ C83.39

Human immunodeficiency virus [HIV] disease; Diffuse large B-cell lymphoma, extranodal and solid organ sites

C81.00 – C81.09

Nodular lymphocyte predominant Hodgkin lymphoma

C81.10 – C81.19

Nodular sclerosis classical Hodgkin lymphoma

C81.20 – C81.29

Mixed cellularity classical Hodgkin lymphoma

C81.30 – C81.39

Lymphocyte depleted classical Hodgkin lymphoma

C81.40 – C81.49

Lymphocyte-rich classical Hodgkin lymphoma

C81.70 – C81.79

Other classical Hodgkin lymphoma

C81.90 – C81.99

Hodgkin lymphoma, unspecified

C82.90 – C82.99

Follicular lymphoma, unspecified

C83.10 – C83.19

Mantle Cell lymphoma

C83.30 – C83.39

Diffuse large B-cell lymphoma

C83.50 – C83.59

Lymphoblastic (diffuse) lymphoma

C83.80 – C83.89

Other non-follicular lymphoma

C84.40 – C84.49

Peripheral T-cell lymphoma, not classified

C84.60 – C84.69

Anaplastic large cell lymphoma, ALK-positive

C84.70 – C84.79

Anaplastic large cell lymphoma, ALK-negative

C85.80 – C85.89

Other specified types of non-Hodgkin lymphoma

C88.0

Waldenström macroglobulinemia

C88.8

Other malignant immunoproliferative diseases

C90.00

Multiple myeloma not having achieved remission

C90.02

Multiple myeloma in relapse

C90.10

Plasma cell leukemia not having achieved remission

C90.12

Plasma cell leukemia in relapse

C90.20

Extramedullary plasmacytoma not having achieved remission

C90.22

Extramedullary plasmacytoma in relapse

C90.30

Solitary plasmacytoma not having achieved remission

C90.32

Solitary plasmacytoma in relapse

C91.10

Chronic lymphocytic leukemia of B-cell type not having achieved remission

C91.12

Chronic lymphocytic leukemia of B-cell type in relapse

D47.Z9

Other specified neoplasms of uncertain behavior of lymphoid, hematopoietic and related tissue

REIMBURSEMENT INFORMATION:

Refer to section entitled POSITION STATEMENT.

PROGRAM EXCEPTIONS:

Federal Employee Program (FEP): Follow FEP guidelines.

State Account Organization (SAO): Follow SAO guidelines.

Medicare Advantage Products: No National Coverage Determination (NCD) was found at the time of the last guideline revised date. The following Local Coverage Determination (LCD) was reviewed on the last guideline revised date: bendamustine (Treanda), (L33268) located at fcso.com.

DEFINITIONS:

None.

RELATED GUIDELINES:

Bortezomib (Velcade) Injection, 09-J0000-92
Doxorubicin HCl Liposome (Doxil) Injection, 09-J0000-91

Ibrutinib (Imbruvica), 09-J2000-09

Idelalisib (Zydelig) Oral Tablet - 09-J2000-23

Lenalidomide (Revlimid), 09-J0000-08

Obinutuzumab (Gazyva), 09-J2000-07

Procarbazine (Matulane) Capsules, 09-J1000-59

Rituximab (Rituxan), 09-J0000-59

Thalidomide (Thalomid) Capsules, 09-J1000-56

Vorinostat (Zolinza) Capsules, 09-J1000-54

OTHER:

None.

REFERENCES:

  1. Bendeka (bendamustine) [package insert]. Teva Pharmaceuticals USA, Inc. North Wales (PA): December 2015.
  2. Clinical Pharmacology [database online]. Tampa, FL: Gold Standard, Inc.; 2016. URL www.clinicalpharmacilogy-ip.com. Accessed 4/25/16.
  3. Micromedex® Healthcare Series [Internet Database]. Greenwood Village, Colo: Thomson Healthcare. Updated periodically. Accessed 4/25/16.
  4. National Comprehensive Cancer Network. Cancer Guidelines. Cancer Guidelines and Drugs and Biologics Compendium. Accessed 4/25/16.
  5. National Comprehensive Cancer Network®. NCCN clinical practice guidelines in oncology (NCCN Guidelines®).B-cell Lymphomas (Version 1.2017) [cited 2016 Dec 16]. Available from: https://www.nccn.org/professionals/physician_gls/pdf/b-cell.pdf
  6. National Comprehensive Cancer Network®. NCCN clinical practice guidelines in oncology (NCCN Guidelines®). Hairy Cell Leukemia [cited 2016 Dec 19]. Available from: https://www.nccn.org/professionals/physician_gls/pdf/hairy_cell.pdf
  7. National Comprehensive Cancer Network®. NCCN clinical practice guidelines in oncology (NCCN Guidelines®). Hodgkin's Lymphoma (Version 1.2016) [cited 2016 April 1]. Available from: https://www.nccn.org/professionals/physician_gls/pdf/hodgkins.pdf
  8. National Comprehensive Cancer Network®. NCCN clinical practice guidelines in oncology (NCCN Guidelines®). Primary Cutaneous B-cell Lymphomas [cited 2016 Dec 19]. Available from: https://www.nccn.org/professionals/physician_gls/pdf/pcbcl.pdf
  9. National Comprehensive Cancer Network®. NCCN clinical practice guidelines in oncology (NCCN Guidelines®). T-cell Lymphomas [cited 2016 Dec 19]. Available from: https://www.nccn.org/professionals/physician_gls/pdf/t-cell.pdf
  10. National Comprehensive Cancer Network®. NCCN clinical practice guidelines in oncology (NCCN Guidelines®). Waldenström's Macroglobulinemia / Lymphoplasmacytic Lymphoma (Version 1.2016) [cited 2016 April 1]. Available from: http://www.nccn.org/professionals/physician_gls/f_guidelines.asp.
  11. Orphan Drug Designations and Approval [Internet]. Silver Spring (MD): US Food and Drug Administration; 2016 [cited 2016 April 1]. Available from: http://www.accessdata.fda.gov/scripts/opdlisting/oopd/index.cfm/.
  12. Sehn LH, Chua N, Mayer J, et al. Obinutuzumab plus bendamustine versus bendamustine monotherapy in patients with rituximab-refractory indolent non-Hodgkin lymphoma (GADOLIN): a randomised, controlled, open-label, multicentre, phase 3 trial. Lancet Oncol. 2016 Aug;17(8):1081-93.
  13. Treanda (bendamustine) [package insert]. Teva Pharmaceuticals USA, Inc. North Wales (PA): November 2015.

COMMITTEE APPROVAL:

This Medical Coverage Guideline (MCG) was approved by the BCBSF Pharmacy Policy Committee on 05/11/16.

GUIDELINE UPDATE INFORMATION:

06/15/14

New Medical Coverage Guideline.

06/15/15

Review and revision to guideline; consisting of updating position statement, dosing/administration, coding, and references.

10/01/15

Revision consisting of update to Program Exceptions section.

03/15/16

Revision consisting of update to description, dosage/administration, coding/billing, and references.

06/15/16

Review and revision to guideline consisting of updating the position statement and references.

01/01/17

Revision: added HCPCS code J9034.

02/15/17

Revision to guideline consisting of updating the description, position statement, and references based on an update to the NCCN guidelines for B-cell lymphomas.

Date Printed: June 25, 2017: 01:12 PM