Subject:
Ofatumumab (Arzerra)
Description:
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IMPORTANT NOTE:
The purpose of this policy is to provide general information applicable to the administration of health benefits that Horizon Blue Cross Blue Shield of New Jersey and Horizon Healthcare of New Jersey, Inc. (collectively “Horizon BCBSNJ”) insures or administers. If the member’s contract benefits differ from the medical policy, the contract prevails. Although a service, supply or procedure may be medically necessary, it may be subject to limitations and/or exclusions under a member’s benefit plan. If a service, supply or procedure is not covered and the member proceeds to obtain the service, supply or procedure, the member may be responsible for the cost. Decisions regarding treatment and treatment plans are the responsibility of the physician. This policy is not intended to direct the course of clinical care a physician provides to a member, and it does not replace a physician’s independent professional clinical judgment or duty to exercise special knowledge and skill in the treatment of Horizon BCBSNJ members. Horizon BCBSNJ is not responsible for, does not provide, and does not hold itself out as a provider of medical care. The physician remains responsible for the quality and type of health care services provided to a Horizon BCBSNJ member.
Horizon BCBSNJ medical policies do not constitute medical advice, authorization, certification, approval, explanation of benefits, offer of coverage, contract or guarantee of payment.
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Chronic lymphocytic leukemia (CLL) is the accumulation of small, mature-appearing, functionally incompetent white blood cells in the bone marrow and blood. As per the National Cancer Institute, 15,000 people are diagnosed with CLL annually. CLL most commonly affects older adults. Current monoclonal antibodies to treat CLL include alemtuzumab (Campath) and rituximab (Rituxan).
Ofatumumab, (ArzerraTM) is a CD20-directed cytolytic monoclonal antibody has an FDA indication for patients with chronic lymphocytic leukemia refractory to fludarabine and alemtuzumab. Ofatumumab, (ArzerraTM), was evaluated in a pivotal, single-arm, open-label, multicenter trial in 154 patients with fludarabine-refractory CLL. The primary endpoint was durable objective tumor response rate determined by the National Cancer Institute Working Group (NCIWG) Guidelines for CLL. Eighty-eight percent of patients received at least eight infusions of ofatumumab while 54% received 12 infusions. The overall response rate in patients with fludarabine-refractory CLL was 42% with a median duration response of 6.5 months.
The package insert for ofatumumab (Arzerra™) was updated on September 24, 2013 to include revisions to the boxed warning, dosage and administration, warnings/precautions sections regarding Progressive Multifocal Leukoencephalopathy (PML) and Hepatitis B reactivation. Dosage and administration was revised to include that ofatumumab (Arzerra™) should be administered where facilities can adequately monitor and treat infusion reactions. Tumor Lysis Syndrome was added to the warnings and precautions section. Administer aggressive intravenous hydration and anti-hyperuricemic agents, correct electrolyte abnormalities, and monitor renal function.
On April 17, 2014, the package insert for ofatumumab (Arzerra™) was updated to include a new indication: ofatumumab, in combination with chlorambucil, for the treatment of previously untreated patients with chronic lymphocytic leukemia (CLL) for whom fludarabine-based therapy is considered inappropriate. The Warnings and Precautions section was revised to include updated information on cytopenias. Severe cytopenias, including neutropenia, thrombocytopenia, and anemia, can occur with Arzerra™. Pancytopenia, agranulocytosis, and fatal neutropenic sepsis have occurred in patients who received Arzerra™ in combination with chlorambucil. Grade 3 or 4 late-onset neutropenia (onset at least 42 days after last treatment dose) and/or prolonged neutropenia (not resolved between 24 and 42 days after last treatment dose) were reported in patients who received Arzerra™.
On January 19, 2016, the FDA approved Arzerra™ for extended treatment of patients who are in complete or partial response after at least two lines of therapy for recurrent or progressive chronic lymphocytic leukemia (CLL). This new approval was based on demonstration of an improvement in progression-free survival (PFS) in a randomized, open-label trial comparing ofatumumab to observation in patients whose disease had a complete or partial response after at least two lines of prior therapy. A total of 474 patients were randomized (1:1) to Arzerra™ or observation. The median age was 64.5 years. Patients in the Arzerra™ arm had received a median of 2 prior therapies (range 2-5). The investigator-assessed median PFS was 29.4 months and 15.2 months in the Arzerra™ and observation arms, respectively.
[INFORMATIONAL NOTE: The FDA-approved Ofatumumab, (ArzerraTM) package insert has the following black box warning:
HEPATITIS B VIRUS REACTIVATION AND PROGRESSIVE MULTIFOCAL LEUKOENCEPHALOPATHY Hepatitis B Virus (HBV) reactivation can occur in patients receiving CD20-directed cytolytic antibodies, including ARZERRA, in some cases resulting in fulminant hepatitis, hepatic failure, and death. Progressive Multifocal Leukoencephalopathy (PML) resulting in death can occur in patients receiving CD20-directed cytolytic antibodies, including Arzerra™.]
Policy:
(NOTE: For Medicare Advantage, please refer to the Medicare Coverage Section below for coverage guidance)
The requirements of the Horizon BCBSNJ Ofatumumab (Arzerra) Program may require a precertification/prior authorization via MagellanRx Management. These requirements are member-specific: please verify member eligibility and requirements through the Horizon Provider Portal (www.horizonblue.com/provider). Ordering clinicians should request pre-certification from MagellanRx Management at ih.magellanrx.com or call 1-800-424-4508 (when applicable).
I. Prior to initiation of Ofatumumab (ArzerraTM) members must have been evaluated and screened for the presence of hepatitis B virus (HBV)
II. Ofatumumab (ArzerraTM) must not be administered concurrently with live vaccines
III. The prescriber is a specialist in the area of the patient’s diagnosis (e.g. oncologist, hematologist) or has consulted with a specialist in the area of the patient’s diagnosis.
IV. Ofatumumab (ArzerraTM) is considered medically necessary based on the FDA indication for adult patients with
- Chronic lymphocytic leukemia (CLL) refractory to fludarabine and alemtuzumab; OR
- In combination with fludarabine and cyclophosphamide for the treatment of patients with relapsed CLL; OR
- In combination with chlorambucil, for the treatment of previously untreated patients with chronic lymphocytic leukemia (CLL) for whom fludarabine-based therapy is considered inappropriate; OR
- Extended treatment of patients who are in complete or partial response after at least two lines of therapy for recurrent or progressive chronic lymphocytic leukemia (CLL)
V. When ofatumumab (ArzerraTM) is medically necessary, therapy will be approved for a period of 6 months based on the following dosing as recommended by FDA product labeling:
- For Refractory CLL:
- Dose 1: 300 mg IV infusion followed 1 week later by
- Doses 2-8: 2,000 mg IV infusion weekly for 7 doses, followed 4 weeks later by
- Doses 9-12: 2,000 mg IV infusion every 4 weeks for 4 doses
- For previously untreated CLL:
- Dose 1: 300 mg on Day 1
- Dose 2: 1,000 mg on Day 8 (Cycle 1)
- Dose 3: 1,000 mg on Day 1 of subsequent 28-day cycles
- Minimum of 3 cycles until best response or a maximum of 12 cycles
- Extended treatment in CLL recommended dosage and schedule is:
- 300 mg on Day 1 followed by
- 1,000 mg 1 week later on Day 8, followed by
- 1,000 mg 7 weeks later and every 8 weeks thereafter for up to a maximum of 2 years.
- For Relapsed CLL:
- Dose 1: 300 mg on Day 1
- Dose 2: 1,000 mg on Day 8 (Cycle 1)
- Dose 3: 1,000 mg on Day 1 of subsequent 28-day cycles for a maximum of 6 cycles
VI. Continuation of ofatumumab (ArzerraTM) is considered for a period of 6 months based on the indication:
- Refractory CLL: there is no clinical evidence on the benefit of Arzerra™ past the initial 12 cycles of therapy unless provisions of extended treatment have been met and the member also meets the following criteria:
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- Member did not develop reactivation of hepatitis B virus indicated by HBsAg and anti-HBc; AND
- Absence of unacceptable toxicity from the drug (e.g.: tumor lysis syndrome, cytopenia, progressive multifocal leukoencephalopathy, hepatitis B virus infection)
- Relapsed CLL: there is no clinical evidence of use beyond initial 6 cycles of therapy unless provisions for extended treatment have been met and the member also meets the following criteria:
- Member did not develop reactivation of hepatitis B virus indicated by HBsAg and anti-HBc; AND
- Absence of unacceptable toxicity from the drug (e.g.: tumor lysis syndrome, cytopenia, progressive multifocal leukoencephalopathy, hepatitis B virus infection)
- Previous untreated CLL: Member must meet all of the following criteria
- Member did not develop reactivation of hepatitis B virus indicated by HBsAg and anti-HBc; AND
- Used in combination with chlorambucil; AND
- Tumor response with stabilization of disease or decrease in size of tumor or tumor spread; AND
- Absence of unacceptable toxicity from the drug (e.g.: tumor lysis syndrome, cytopenia, progressive multifocal leukoencephalopathy, hepatitis B virus infection); AND
- Treatment not to exceed a maximum of 12 cycles
- Extended treatment in CLL: Member must meet all of the following criteria
- Member did not develop reactivation of hepatitis B virus indicated by HBsAg and anti-HBc; AND
- Tumor response with stabilization of disease or decrease in size of tumor or tumor spread; AND
- Absence of unacceptable toxicity from the drug (e.g.: tumor lysis syndrome, cytopenia, progressive multifocal leukoencephalopathy, hepatitis B virus infection); AND
- Treatment not to exceed a maximum of 2 years.
VII. Ofatumumab (ArzerraTM) is considered medically necessary for the following off-label indications that have in effect a rating of 'Category 1' or 'Category 2A' in the current recommendations in the National Comprehensive Cancer Network (NCCN) compendium. Refer to National Comprehensive Cancer Network: Drugs and Biologics Compendium - ofatumumab. Available at: https://www.nccn.org/professionals/drug_compendium/content/.
VI. Ofatumumab (ArzerraTM) is considered investigational for other indications.
Medicare Coverage
There is no National Coverage Determination (NCD). In the absence of an NCD, coverage decisions are left to the discretion of Local Medicare Carriers. Novitas Solutions, Inc, the Local Medicare Carrier for jurisdiction JL, has not issued a determination for this service. Therefore, Medicare Advantage Products will follow the Horizon Policy. See generally, Local Coverage Article: Approved Drugs and Biologicals; Includes Cancer Chemotherapeutic Agents (A53049). Available to be accessed at Novitas Solutions, Inc., Medical Policy Search page: https://www.novitas-solutions.com/webcenter/portal/MedicareJL/pagebyid?contentId=00024370
Medicaid Coverage
For Horizon NJ Health members, please follow this link for the corresponding HNJH drug policy https://services3.horizon-bcbsnj.com/ddn/NJhealthWeb.nsf
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Horizon BCBSNJ Medical Policy Development Process:
This Horizon BCBSNJ Medical Policy (the “Medical Policy”) has been developed by Horizon BCBSNJ’s Medical Policy Committee (the “Committee”) consistent with generally accepted standards of medical practice, and reflects Horizon BCBSNJ’s view of the subject health care services, supplies or procedures, and in what circumstances they are deemed to be medically necessary or experimental/ investigational in nature. This Medical Policy also considers whether and to what degree the subject health care services, supplies or procedures are clinically appropriate, in terms of type, frequency, extent, site and duration and if they are considered effective for the illnesses, injuries or diseases discussed. Where relevant, this Medical Policy considers whether the subject health care services, supplies or procedures are being requested primarily for the convenience of the covered person or the health care provider. It may also consider whether the services, supplies or procedures are more costly than an alternative service or sequence of services, supplies or procedures that are at least as likely to produce equivalent therapeutic or diagnostic results as to the diagnosis or treatment of the relevant illness, injury or disease. In reaching its conclusion regarding what it considers to be the generally accepted standards of medical practice, the Committee reviews and considers the following: all credible scientific evidence published in peer-reviewed medical literature generally recognized by the relevant medical community, physician and health care provider specialty society recommendations, the views of physicians and health care providers practicing in relevant clinical areas (including, but not limited to, the prevailing opinion within the appropriate specialty) and any other relevant factor as determined by applicable State and Federal laws and regulations.
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Index:
Ofatumumab
Arzerra
Chronic lymphocytic leukemia
References:
1. ArzerraTM Prescribing Information. Novartis Pharmaceuticals Corporation. East Hanover, NJ. August 2016.
2. National Comprehensive Cancer Network: Drugs and Biologics Compendium. Ofatumumab. 2019. Available at: https://www.nccn.org/professionals/drug_compendium/content/. [Accessed 03/21/2020].
3. National Comprehensive Cancer Network (NCCN). Practice Guidelines in Oncology: Non-Hodgkin’s Lymphoma. Version 1.2013. Available at:http://www.nccn.org/professionals/physician_gls/PDF/nhl.pdf [ Accessed 4 Feb 2013].
4. Gold Standard, Inc. Arzerra. Clinical Pharmacology [database online]. Available at: http://www.clinicalpharmacology.com. Accessed: March 30, 2019.
5. Micromedex® Healthcare Series. Thomson Healthcare, Greenwood Village, CO. April 2010. Available at: http://www.thomsonhc.com Accessed March 30, 2019.
6. AHFS Consumer Medication Information. Bethesda (MD): American Society of Health-System Pharmacists, Inc.; 2009. Arzerra; [Accessed March 30, 2019]
7. Coiffer B, Lepretre S, Pedersen LM, et al. 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.
8. ClinicalTrials.gov. Ofatumumab dose-finding in RRMS patients. December 2009. [Available at: http://clinicaltrials.gov/ct2/show/NCT00640328?term=ofatumumab&rank=3 ].
9. ClinicalTrials.gov. HuMax-CD20 in active rheumatoid arthritis. September 2009. [Available at: http://clinicaltrials.gov/ct2/show/NCT00291928?term=ofatumumab&rank=22].
10. ClinicalTrials.gov. Study to evaluate SC route of administration of ofatumumab in RA patients. [Available at: http://clinicaltrials.gov/ct2/show/NCT00686868?term=ofatumumab&rank=18 ].
11. ClinicalTrials.gov. Investigating clinical efficacy of ofatumumab in adult RA patients who had an inadequate response to MTX therapy. [Available at: http://clinicaltrials.gov/ct2/show/NCT00611455?term=ofatumumab&rank=9 ].
12. ClinicalTrials.gov. Ofatumumab in patients with relapsed/progressive diffused large B-cell lymphoma (DLBCL) ineligible for or relapse/progression after transplant. [ Available at http://clinicaltrials.gov/ct2/show/NCT00622388?term=ofatumumab&rank=16 ].
13. ClinicalTrials.gov. A Phase II trial of ofatumumab in subjects with Waldenstrom’s macroglobulinemia. [Available at: http://clinicaltrials.gov/ct2/show/NCT00811733?term=ofatumumab&rank=14 ].
14. ClinicalTrials.gov. Ofatumumab (Humax-CD20) with CHOP in FL patients. [Available at: http://clinicaltrials.gov/ct2/show/NCT00494780?term=ofatumumab&rank=12 ].
15. ClinicalTrials.gov. Ofatumumab in Japanese Patients with CD20 Positive Follicular Lymphoma or chronic Lymphocytic Leukemia. [Available at: http://clinicaltrials.gov/ct2/show/NCT00742144?term=ofatumumab+and+follicular&rank=1].
16. ClinicalTrials.gov. Single Agent Ofatumumab Vs. Single Agent Rituximab in Follicular Lymphoma Relapsed After Rituximab-Containing Therapy. [Available at: http://clinicaltrials.gov/ct2/show/NCT01200589?term=ofatumumab+and+follicular&rank=2].
17. ClinicalTrials.gov. Ofatumumab in Treating Patients with Previously Untreated Stage II, Stage III, or Stage IV Follicular Non-Hodgkin Lymphoma. [Available at: http://clinicaltrials.gov/ct2/show/NCT01190449?term=ofatumumab+and+follicular&rank=4].
18. ClinicalTrials.gov. Dexamethasone, Ofatumumab and Bendamustine (DOT) First-line in Mantle-cell Lymphoma (MCL). [Available at: http://clinicaltrials.gov/ct2/show/NCT01221103?term=ofatumumab+mantle-cell&rank=1].
19. ClinicalTrials.gov. Lenalidomide and Ofatumumab in Previously Treated Chronic Lymphocytic leukemia and Small Lymphocytic Lymphoma (CLL/SLL). [Available at: http://clinicaltrials.gov/ct2/show/NCT01002755?term=ofatumumab+SLL&rank=1].
20. ClinicalTrials.gov. A Phase II Study of Ofatumumab-Based Induction Chemoimmunotheraphy Followed by Consolidation Ofatumumab Immunotherapy in Previously Untreated Patients With Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma. [Available at: http://clinicaltrials.gov/ct2/show/NCT01145209?term=ofatumumab+SLL&rank=2].
21. National Comprehensive Cancer Network (NCCN). Practice Guidelines in Oncology: Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma - Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma. Version 2020. Available at: https://www.nccn.org/professionals/physician_gls/pdf/cll.pdf [ Accessed March 21, 2019].
22. National Comprehensive Cancer Network (NCCN). Practice Guidelines in Oncology: B-Cell Lymphomas. Version 2020. Available at: https://www.nccn.org/professionals/physician_gls/pdf/b-cell.pdf [Accessed March 21, 2020].
Codes:
(The list of codes is not intended to be all-inclusive and is included below for informational purposes only. Inclusion or exclusion of a procedure, diagnosis, drug or device code(s) does not constitute or imply authorization, certification, approval, offer of coverage or guarantee of payment.)
CPT*
HCPCS
* CPT only copyright 2020 American Medical Association. All rights reserved. CPT is a registered trademark of the American Medical Association.
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Medical policies can be highly technical and are designed for use by the Horizon BCBSNJ professional staff in making coverage determinations. Members referring to this policy should discuss it with their treating physician, and should refer to their specific benefit plan for the terms, conditions, limitations and exclusions of their coverage.
The Horizon BCBSNJ Medical Policy Manual is proprietary. It is to be used only as authorized by Horizon BCBSNJ and its affiliates. The contents of this Medical Policy are not to be copied, reproduced or circulated to other parties without the express written consent of Horizon BCBSNJ. The contents of this Medical Policy may be updated or changed without notice, unless otherwise required by law and/or regulation. However, benefit determinations are made in the context of medical policies existing at the time of the decision and are not subject to later revision as the result of a change in medical policy
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