Notification



Notification Issue Date:



Medical Policy Bulletin


Title:Ofatumumab (Arzerra™)

Policy #:08.00.88e

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


The Company makes decisions on coverage based on Policy Bulletins, benefit plan documents, and the member’s medical history and condition. 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.

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 Medical Policy Bulletin document describes the status of medical technology at the time the document was developed. Since that time, new technology may have emerged or new medical literature may have been published. This Medical Policy Bulletin will be reviewed regularly and be updated as scientific and medical literature becomes available. For more information on how Medical Policy Bulletins are developed, go to the About This Site section of this Medical Policy Web site.



Policy

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

MEDICALLY NECESSARY

Ofatumumab (Arzerra™) is considered medically necessary and, therefore, covered for the treatment of any of the following indications:

CHRONIC LYMPHOCYTIC LEUKEMIA/SMALL LYMPHOCYTIC LYMPHOMA
  • First-line therapy in combination with chlorambucil for chronic lymphocyitc leukemia/small lymphocytic lyphoma (CLL/SLL) without del(17p)/TP53 mutation in:
    • Individuals age 65 years or older
    • Individuals younger than 65 years with significant comorbidities*
    • Frail individuals unable to tolerate purine analogs who have indications for treatment**
  • First-line therapy in combination with bendamustine for CLL/SLL without del(17p)/TP53 mutation in:
    • Individuals age 65 years or older
    • Individuals younger than 65 years with or without significant comorbidities* who have indications for treatment**
  • Therapy for relapsed or refractory disease in individuals with indications for treatment**
    • Without del(17p)/TP53 mutation:
      • In combination with fludarabine and cyclophosphamide in individuals less than 65 years of age without significant comorbidities*
      • As a single agent
    • With del(17p)/TP53 mutation:
      • As a single agent for individuals with lymph nodes less than 5 cm
  • For extended treatment of individuals who are in complete or partial response after at least two lines of therapy for recurrent of progressive CLL
  • For the treatment of individuals with CLL refractory to fludarabine and alemtuzumab

* Based on the modified cumulative illness rating scale (CIRS), Charlson Comorbidity Scale, or the NCI Comorbidity Index

** Indications for treatment are as follows:
  • Significant disease-related symptoms: severe fatigue, night sweats, weight loss, fever without infection
  • Threatened end-organ function
  • Progressive bulky disease (spleen more than 6 cm below the costal margin, lymph nodes greater than 10 cm)
  • Progressive anemia
  • Progressive thrombocytopenia (platelet counts greater than 100,000 cells/ mm3 are typically not associated with clinical risk)
  • Absolute lymphocyte count above 200-300 x109/L or symptoms related to leukostasis

WALDENSTRÖM'S MACROGLOBULINEMIA/LYMPHOPLASMACYTIC LYMPHOMA

Waldenström's macroglobulinemia/lymphoplasmacytic lymphoma as single-agent or combination therapy in rituximab-intolerant individuals for previously treated disease that does not respond to primary therapy or for progressive or relapsed disease

EXPERIMENTAL/INVESTIGATIONAL

All other uses for ofatumumab (Arzerra™) 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.
Guidelines

CHARLSON COMORBIDITY SCALE

The Charlson Comorbidity Scale was developed in 1987 based on one-year mortality data from internal medicine individuals admitted to a single New York hospital. The scale takes into account 19 medical conditions (e.g., myocardial infarction and moderate-severe liver disease) weighted 1-6 on the basis of their relative risk of death within 12 months, with total scores ranging from 0-37. The total sum and the individual's age are used to determine the Charlson score. That score is then used to calculate the probability of survival.

MODIFIED CUMULATIVE ILLNESS RATING SCALE (CIRS)

The Modified Cumulative Illness Rating Scare (CIRS) is a tool to measure comorbidity by measuring the chronic medical illness burden while taking into account the severity of chronic disease. CIRS evaluates 14 biological systems on a 0-4 scale, ranging from absence of disorders to acute organ insufficiency requiring emergency therapy. The comorbidity index was calculated as the number of categories with a score of 2 or greater, including psychiatric.

NCI COMORBIDITY INDEX

The NCI Comorbidity Index is a modified version of the Charlson Comorbidity Scale, not taking into account the individual's age. Eleven medical conditions (i.e., DM, CAD, CVA, PVD, other cardiac disease, dysrhythmia, COPD, GI bleeding, liver disease, cancer and CHF) are weighed 1-6. The score is used to determine the probability of survival.

BLACK BOX WARNINGS

Refer to the specific manufacturer's prescribing information for any applicable Black Box Warnings.

BENEFIT APPLICATION

Subject to the terms and conditions of the applicable benefit contract, ofatumumab (Arzerra™) is covered under the medical benefits of the Company’s products when the medical necessity criteria listed in this medical policy are met.

US FOOD AND DRUG ADMINISTRATION (FDA)

Ofatumumab (Arzerra™) was approved by the FDA on October 26, 2009, for the treatment of chronic lymphocytic leukemia (CLL) refractory to fludarabine and alemtuzumab. Supplemental approvals for ofatumumab (Arzerra™) have since been issued by the FDA.

Description

Chronic lymphocytic leukemia (CLL) is the most common type of leukemia and one of the most common malignant lymphoid diseases found in the Western world. CLL causes a slow overgrowth of white blood cells (B lymphocytes) in the bone marrow that spreads to the blood. This overgrowth then spreads to lymph nodes and other organs. CLL eventually leads to the failure of the bone marrow, which then leads to weakening of the immune system.

Ofatumumab (Arzerra™), an intravenous humanized monoclonal antibody, was approved by the US Food and Drug Administration (FDA) by accelerated process in October 2009 for the treatment of CLL that is refractory to fludarabine (Fludara®) and alemtuzumab (Campath®). In January 2016, ofatumumab (Arzerra™) was approved for the extended treatment of individuals who are in complete or partial response after at least two lines of therapy for recurrent or progressive CLL. Arzerra was approved in August 2016 to be used in combination with fludarabine and cyclophosphamide for the treatment of individuals with relapsed CLL.

Ofatumumab (Arzerra™) targets a distinct antibody-binding site of the CD20 transmembrane protein on the cell membrane of B cells. CD20 is expressed on normal mature B lymphocytes and B cell CLL, not on early B-cell progenitors or mature plasma cells. It is suggested that the binding of ofatumumab (Arzerra™) to the CD20 molecule results in B-cell lysis by complement-dependent cytotoxicity or antibody-dependent cell-mediated cytotoxicity. The CD20 molecule is a key target in CLL therapy because it is expressed in most cancers affecting the B cell.

The efficacy of ofatumumab (Arzerra™) was evaluated in 447 individuals previously untreated for CLL in a randomized, open-label, parallel-arm study. The individuals were randomized to receive either ofatumumab (Arzerra™) with chlorambucil or chlorambucil alone. The primary efficacy endpoint was progression-free survival; the secondary efficacy endpoints were overall response, complete response, and duration of response. Ofatumumab (Arzerra™) with chlorambucil had a statistically significant improvement in median progression-free survival compared to the control (22.4 months versus 13.1 months). The overall response was statistically higher for the ofatumumab (Arzerra™) group compared to the control group (82.4% versus 68.6%). The complete response (12% ofatumumab (Arzerra™) group, 1% control group) and duration of response (median months 22.1 ofatumumab (Arzerra™) group, 13.2 control group) was significantly better for the ofatumumab (Arzerra™) group compared to the chlorambucil alone group.

A single-arm, multicenter study evaluated the efficacy of ofatumumab (Arzerra™) in 154 individuals with relapsed or refractory CLL. The main efficacy outcome was durable objective tumor response rate. The overall response rate in individuals with CLL refractory to fludarabine and alemtuzumab (Campath®) was 42% with a median duration of response of 6.5 months. There were no complete responses.

An open-label, randomized, parallel-arm, multicenter phase 3 study (COMPLEMENT 2) evaluated the efficacy of ofatumumab (Arzerra) in combination with fludarabine and cyclophosphamide versus only fludarabine and cyclophosphamide in 365 individuals with relapsed CLL. The primary endpoint was progression-free survival. The study found that adding ofatumumab to the fludarabine and cyclophosphamide regimen resulted in a statistically significant 10 month improvement in median progression-free survival versus the fludarabine and cyclophosphamide combination alone (28.9 months vs. 18.8 months).

Efficacy of ofatumumab (Arzerra) for extended treatment in CLL was evaluated in a randomized, parallel-arm, open label study in 474 individuals. These individuals had a complete or partial response after at least two lines of therapy. This trial studied individuals who received ofatumumab (Arzerra) for extended treatment versus those without further treatment after having a complete or partial response post treatment for relapsed CLL. The primary outcome of this trial was progression-free survival. The median PFS was 29.4 months in the ofatumumab (Arzerra) arm and 15.2 months in the observation arm.

Efficacy of ofatumumab (Arzerra) in individuals with CLL refractory to fludarabine and alemtuzumab was studied in a single-arm, multicenter trial consisting of 154 individuals. Drug refractoriness was defined as failure to achieve a partial response to, or disease progression within 6 months of, the last dose of fludarabine or alemtuzumab. Objective tumor response, determine by using the National Cancer Institute-sponsored working group (NCI-WG) guidelines for CLL, was the primary outcome. The study found that 42% of the individuals treated with ofatumumab achieved a partial response, with a 6.5 month median duration of response.

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). Ofatumumab (Arzerra™). AHFS Drug Information 2016. [Lexicomp Online Web Site]. 03/22/2018. Available at:http://online.lexi.com/lco/action/search?q=arzerra&t=name {via subscription only]. Accessed October 16, 2018.

Bauer K, Rancea M, Roloff V, et al. Rituximab, ofatumumab and other monoclonal anti-CD20 antibodies for CLL. The Cochrane Collaboration. 2012.

Coiffer B, Lepretre S, Pederson L. Safety and efficacy of ofatumumab, a fully human monoclonal anti-CD20 antibody, in patients with relapsed or refractory B-cell chronic lymphocytic leukemia: a phase 1-2 study. Blood. 2008;111:1094-1100.

Deschodt M, Devriendt E, Sabble M, et al. Characteristics of older adults admitted to the emergency department (ED) and their risk factors for ED readmission based on comprehensive geriatric assessment: a prospective cohort study. BMC Geriatr.
2015;15:54.

Elsevier Gold's Standard Clinical Pharmacology Compendium. Ofatumumab. [MD Consult Web site]. 02/22/2018. Available at: https://www.clinicalkey.com/#!/content/drug_monograph/6-s2.0-3658. [via subscription only]. Accessed October 16, 2018.

Hanlon K, Ellard S, Rudin C, et al. Evaluation of 13q14 status in patients with chronic lymphocytic leukemia using single nucleotide polymorphism-based techniques. J Mol Diagn. 2009;11:298-305.

Kastner C, Armitage J, Kimble A, et al. The Charlson comorbidity score: a superior comorbidity assessment tool for the prostate cancer multidisciplinary meeting. Prostate Cancer and Prostatic Diseases. 2006;9:270-274.

Lexi-Drugs Compendium. Arzerra. 09/29/2018. [Lexicomp Online Web site]. Available at: http://online.lexi.com/lco/action/home [via subscription only]. Accessed October 16, 2018.

Liu J, Huang Z, Gilbertson D. et al. An improved comorbidity index for outcome analyses among dialysis patients. Kidney International. 2010;77:141-151.

Maloney D. Anti-CD20 antibody therapy for B-cell lymphomas. NEJM. 2012;366(21):2008-16.

Micromedex2.0® Healthcare Series. DrugDex®. Ofatumumab (Arzerra™). [Micromedex® Web site]. 07/06/2018. Available at: http://www.micromedexsolutions.com/home/dispatch [via subscription only]. Accessed October 16, 2018.

National Comprehensive Cancer Network (NCCN). Ofatumumab (Arzerra™). Drugs and Biologics Compendium™. [NCCN Web site]. 2018. [via subscription only]. Available at: http://www.nccn.org. Accessed October 16, 2018.

National Comprehensive Cancer Network (NCCN). Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma Guidelines. [NCCN Web site]. v2.2019.10/05/2018. [via subscription only]. Available at: http://www.nccn.org. Accessed October 16, 2018.

National Comprehensive Cancer Network (NCCN). Waldenström's Macroglobulinemia/ Lymphoplasmacytic Lymphoma Guidelines. [NCCN Web site].v2.2019. 09/14/2018. [via subscription only]. Available at: http://www.nccn.org. Accessed October 16, 2018.

National Institute for Health and Clinical Excellence (NICE). Ofatumumab for the treatment of chronic lymphocytic leukaemia refractory to fludarabine and alemtuzumab (tech appraisal). [NICE Web site]. October 2010. Available at: https://www.nice.org.uk/guidance/ta202 Accessed October 16, 2018.

National Institute for Health and Clinical Excellence (NICE). Ofatumumab in combination with chlorambucil or bendamustine for untreated chronic lymphocytic leukaemia (tech appraisal). [NICE Web site]. June 2015. Available at: https://www.nice.org.uk/guidance/ta344. Accessed October 16, 2018.

O'Brien S, Osterborg A. Ofatumumab: a new CD20 monoclonal antibody therapy for B-cell CLL. Clin Lymph Myel Leuk. 2010;10(5):361-368.

Ofatumumab (Arzerra™) [prescribing information]. East Hanover, NJ. Novartis; 08/2016. Available online at:https://www.pharma.us.novartis.com/sites/www.pharma.us.novartis.com/files/arzerra.pdf. Accessed October 16, 2018.

Salvi F, Miller M, Grilli A, et al. A manual of guidelines to score the modified cumulative illness rating scale and its validation in acute hospitalized elderly patients. J Am Geriatri Soc. 2008;56:1926-1931.

US Food and Drug Administration (FDA). Center for Biologics Evaluation and Research. Ofatumumab (Arzerra™). BLA Accelerated approval letter. [FDA Web site].10/26/2009. Available at:
http://www.accessdata.fda.gov/drugsatfda_docs/appletter/2009/125326s000ltr.pdf. Accessed October 16, 2018.

US Food and Drug Administration (FDA). Center for Biologics Evaluation and Research. Ofatumumab (Arzerra™). Supplemental approval letter. [FDA Web site].04/17/2014. Available at:
http://www.accessdata.fda.gov/drugsatfda_docs/appletter/2014/125326Orig1s060ltr.pdfAccessed October 16, 2018.

US Food and Drug Administration (FDA). Center for Drug Evaluation and Research. Drugs@FDA. Drug details: Ofatumumab (Arzerra™). [FDA Web site]. Available at: http://www.accessdata.fda.gov/scripts/cder/daf/index.cfm?event=BasicSearch.process. Accessed October 16, 2018.

Wierda W, Kipps T, Mayer J, et al. Ofatumumab as single-agent CD20 immunotherapy in fludarabine-refractory chronic lymphocytic leukemia. J Clin Oncol. 2010;28(10):1749-1755.





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

C88.0 Waldenstrom macroglobulinemia

C91.10 Chronic lymphocytic leukemia of B-cell type not having achieved remission

C91.11 Chronic lymphocytic leukemia of B-cell type in remission

C91.12 Chronic lymphocytic leukemia of B-cell type in relapse




HCPCS Level II Code Number(s)

J9302 Injection, ofatumumab, 10 mg


Revenue Code Number(s)

N/A

Coding and Billing Requirements


Cross References


Policy History

Revisions from 08.00.88e
12/17/2018The criteria section for chronic lymphocytic leukemia/small lymphocytic lymphoma has been updated to address recommendations from the National Comprehensive Cancer Network.


Effective 10/05/2017 this policy has been updated to the new policy template format.


Version Effective Date: 12/17/2018
Version Issued Date: 12/17/2018
Version Reissued Date: N/A

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