BlueCross BlueShield of Tennessee Medical Policy Manual

Bendamustine Products (Treanda®, Belrapzo®, Bendeka®)

NDC CODE(S)

63459-0390-XX TREANDA 25MG Solution Reconstituted (CEPHALON)

63459-0391-XX TREANDA 100MG Solution Reconstituted (CEPHALON)

42367-0521-XX BELRAPZO 100MG/4ML Solution (EAGLE PHARMACEUTICALS)

63459-0348-XX BENDEKA 25MG/ML Solution (CEPHALON)

DESCRIPTION

Bendamustine, classified as a bifunctional alkylating agent, is a nitrogen mustard analogue.  It is an antineoplastic agent whose exact mechanism of action is unknown.  As an alkylating agent it interferes with DNA replication and the transcription of RNA which ultimately disrupts nucleic acid function.  In this respect, bendamustine has produced more DNA double-strand breaks than other alkylating agents.  It may also activate apoptosis by inhibiting mitosis, with DNA-damaged cells undergoing a premature form of necrotic cell death known as mitotic catastrophe. 

Note: This policy combines all bendamustine products (innovator & biosimilars) into one policy.

POLICY

MEDICAL APPROPRIATENESS

INITIAL APPROVAL CRITERIA

Non-Hodgkin’s Lymphoma (NHL)

The following T-Cell Lymphomas

Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma (CLL/SLL)

Waldenström’s Macroglobulinemia/Lymphoplasmacytic Lymphoma (WM/LPL)

Adult Hodgkin Lymphoma (cHL)

Pediatric Hodgkin Lymphoma (pHL)

* Pediatric Hodgkin Lymphoma may be applicable to adolescent and young adult (AYA) patients up to the age of 39 years.

Multiple Myeloma

RENEWAL CRITERIA

Authorizations cannot be renewed

DOSAGE/ADMINISTRATION

INDICATION

DOSE

Non-Hodgkin’s Lymphoma

Up to 120 mg/m² on days 1 and 2 of a 21-day cycle, up to 8 cycles

CLL/SLL

Up to 100 mg/m² on days 1 and 2 of a 28-day cycle, up to 6 cycles

Waldenström’s Macroglobulinemia/

Lymphoplasmacytic Lymphoma

Up to 90 mg/m2 on days 1 and 2 of a 28-day cycle, up to 6 cycles

cHL

Up to 120 mg/m² on days 1 and 2 of a 28-day cycle, up to 6 cycles

Multiple Myeloma

Up to 100 mg/m² on days 1 and 2 of a 28-day cycle, up to 8 cycles

 

LENGTH OF AUTHORIZATION

 

·         Non-Hodgkin’s Lymphoma (NHL), Chronic Lymphocytic Leukemia (CLL)/Small Lymphocytic Lymphoma (SLL), Waldenström’s Macroglobulinemia (WM)/Lymphoplasmacytic Lymphoma (LPL), Classic Hodgkin Lymphoma (cHL):

·         Multiple Myeloma:

DOSING LIMITS

 

Max Units (per dose and over time) [HCPCS Unit]:

 

NHL:

·         600 billable units every 21 days

WM/LPL:

·         450 billable units every 28 days

cHL:

·         600 billable units every 28 days

CLL/SLL & Multiple Myeloma:

·         500 billable units every 28 days

APPLICABLE TENNESSEE STATE MANDATE REQUIREMENTS

BlueCross BlueShield of Tennessee’s Medical Policy complies with Tennessee Code Annotated Section 56-7-2352 regarding coverage of off-label indications of Food and Drug Administration (FDA) approved drugs when the off-label use is recognized in one of the statutorily recognized standard reference compendia or in the published peer-reviewed medical literature.

IMPORTANT REMINDER

We develop Medical Policies to provide guidance to Members and Providers.  This Medical Policy relates only to the services or supplies described in it.  The existence of a Medical Policy is not an authorization, certification, explanation of benefits or a contract for the service (or supply) that is referenced in the Medical Policy.  For a determination of the benefits that a Member is entitled to receive under his or her health plan, the Member's health plan must be reviewed.  If there is a conflict between the Medical Policy and a health plan, the express terms of the health plan will govern.

ADDITIONAL INFORMATION 

(Note: Frailty may be assessed using a modified geriatric screening tool such as the Fried Frailty Criteria, Balducci Frailty Criteria, Abbreviated CGA (aCGA), etc.) 

For appropriate chemotherapy regimens, dosage information, contraindications, precautions, warnings, and monitoring information, please refer to one of the standard reference compendia (e.g., the NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines®) published by the National Comprehensive Cancer Network®, Drugdex Evaluations of Micromedex Solutions at Truven Health, or The American Hospital Formulary Service Drug Information).

SOURCES 

1.     Treanda [package insert]. North Wales, PA; Cephalon, Inc; November 2019. Accessed January 2021.

2.     Bendeka [package insert]. North Wales, PA; Teva Pharmaceuticals USA, Inc.; November 2020. Accessed January 2021.

3.     Belrapzo [package insert]. Woodcliff, NJ; Eagle Pharmaceuticals, Inc; October 2009. Accessed January 2021.

4.     Referenced with permission from the NCCN Drugs & Biologics Compendium (NCCN Compendium®) for bendamustine. National Comprehensive Cancer Network, 2021. The NCCN Compendium® is a derivative work of the NCCN Guidelines®. NATIONAL COMPREHENSIVE CANCER NETWORK®, NCCN®, and NCCN GUIDELINES® are trademarks owned by the National Comprehensive Cancer Network, Inc. To view the most recent and complete version of the Compendium, go online to NCCN.org. Accessed January 2021.

5.     Moskowitz AJ, Hamlin PA Jr, Perales MA, et al. Phase II study of bendamustine in relapsed and refractory Hodgkin lymphoma. J Clin Oncol. 2013;31(4):456-460.

6.     Kahl BS, Bartlett NL, Leonard JP, et al. Bendamustine is effective therapy in patients with rituximab-refractory, indolent B-cell non-Hodgkin lymphoma: results from a Multicenter Study. Cancer. 2010;116(1):106-114. doi:10.1002/cncr.24714.

7.     Knauf WU, Lissitchkov T, Aldaoud A, et al. Bendamustine compared with chlorambucil in previously untreated patients with chronic lymphocytic leukaemia: updated results of a randomized phase III trial. Br J Haematol. 2012;159(1):67-77. doi:10.1111/bjh.12000.

8.     Rummel MJ, Niederle N, Maschmeyer G, et al. Bendamustine plus rituximab versus CHOP plus rituximab as first-line treatment for patients with indolent and mantle-cell lymphomas: an open-label, multicentre, randomised, phase 3 non-inferiority trial [published correction appears in Lancet. 2013 Apr 6;381(9873):1184]. Lancet. 2013;381(9873):1203-1210. doi:10.1016/S0140-6736(12)61763-2.

9.     O'Connor OA, Lue JK, Sawas A, et al. Brentuximab vedotin plus bendamustine in relapsed or refractory Hodgkin's lymphoma: an international, multicentre, single-arm, phase 1-2 trial. Lancet Oncol 2018; 19:257-266.

10.  Santoro A, Mazza R, Pulsoni A, et al. Bendamustine in Combination With Gemcitabine and Vinorelbine Is an Effective Regimen As Induction Chemotherapy Before Autologous Stem-Cell Transplantation for Relapsed or Refractory Hodgkin Lymphoma: Final Results of a Multicenter Phase II Study. J Clin Oncol 2016; 34:3293.

11.  Budde LE, Wu D, Martin DB, et al. Bendamustine with rituximab, etoposide and carboplatin (T(R)EC) in relapsed or refractory aggressive lymphoma: a prospective multicentre phase ½ clinical trial. Br J Haematol. 2018;183(4):601-607. doi:10.1111/bjh.15585.

12.  Ludwig H, Kasparu H, Leitgeb C, et al. Bendamustine-bortezomib-dexamethasone is an active and well-tolerated regimen in patients with relapsed or refractory multiple myeloma. Blood. 2014;123(7):985-991. doi:10.1182/blood-2013-08-521468.

13.  Lentzsch S, O'Sullivan A, Kennedy RC, et al. Combination of bendamustine, lenalidomide, and dexamethasone (BLD) in patients with relapsed or refractory multiple myeloma is feasible and highly effective: results of phase 1/2 open-label, dose escalation study. Blood. 2012;119(20):4608-4613. doi:10.1182/blood-2011-12-395715.

14.  Knop S, Straka C, Haen M, Schwedes R, Hebart H, Einsele H. The efficacy and toxicity of bendamustine in recurrent multiple myeloma after high-dose chemotherapy. Haematologica. 2005;90(9):1287-1288.

15.  Referenced with permission from the NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines®) for B-Cell Lymphomas 2.2021. National Comprehensive Cancer Network, 2021. NATIONAL COMPREHENSIVE CANCER NETWORK®, NCCN®, and NCCN GUIDELINES® are trademarks owned by the National Comprehensive Cancer Network, Inc. To view the most recent and complete version of the Guidelines, go online to NCCN.org. Accessed February 2021.

16.  Referenced with permission from the NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines®) for Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma 2.2021. National Comprehensive Cancer Network, 2021. NATIONAL COMPREHENSIVE CANCER NETWORK®, NCCN®, and NCCN GUIDELINES® are trademarks owned by the National Comprehensive Cancer Network, Inc. To view the most recent and complete version of the Guidelines, go online to NCCN.org. Accessed February 2021.

17.  Lexi-Comp Online. (2021, February). AHFS DI. Bendamustine hydrochloride. Retrieved March 22, 2021 from Lexi-Comp Online with AHFS.

18.  MICROMEDEX Healthcare Series. Drugdex Drug Evaluations. (2021, March). Bendamustine. Retrieved March 22, 2021 from MICROMEDEX Healthcare Series.

ORIGINAL EFFECTIVE DATE:  3/12/2009

MOST RECENT REVIEW DATE:    7/31/2021

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Policies included in the Medical Policy Manual are not intended to certify coverage availability. They are medical determinations about a particular technology, service, drug, etc. While a policy or technology may be medically necessary, it could be excluded in a member's benefit plan. Please check with the appropriate claims department to determine if the service in question is a covered service under a particular benefit plan. Use of the Medical Policy Manual is not intended to replace independent medical judgment for treatment of individuals. The content on this Web site is not intended to be a substitute for professional medical advice in any way. Always seek the advice of your physician or other qualified health care provider if you have questions regarding a medical condition or treatment.

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