Subject:
Mozobil® (Plerixafor Injection)
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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Mozobil® (plerixafor injection), a bicyclam derivative, is a novel small-molecule that selectively and reversibly antagonizes the CXCR4 chemokine receptor on CD34+ hematopoietic stem cells (HSC). This results in the mobilization of HSC into peripheral blood for collection by apheresis. The peripheral blood stem cells (PBSC) are then used for autologous transplants following ablative chemotherapy.
Current mobilization regimens require collection of at least 2 x 106 CD34+ HSC cells/kg (optimally ≥ 5 x 106 CD34+ HSC cells/kg). Higher yields are preferable and are predictors of successful engraftment and hematologic recovery as well as reduce the need for transfusions, risk of infection, overall costs, and hospital stays. It may also be correlated with improved overall survival.
Use of plerixafor, in addition to G-CSF, has been shown in clinical studies to stimulate peripheral blood stem cells and ultimately improve the yield obtained from apheresis compared to when G-CSF is used alone. Typical failure rates for mobilizing the minimum number of CD34+ cells is approximately 80% for G-CSF and/or GM-CSF, ~70% when used in combination with chemotherapy, but only ~30% when used in combination with plerixafor. The efficacy of plerixafor plus G-CSF is improved for multiple myeloma patients (compared to Non-Hodgkin’s lymphoma); this is likely due to the increased cytotoxicity of the initial chemotherapy NHL patients receive that hinders subsequent response to mobilization.
Results on Phase III studies demonstrate a greater proportion of patients mobilized by G-CSF plus plerixafor proceeding to autologous stem cell transplant compared to those treated with G-CSF alone. Engraftment rates for neutrophil (PMN) and platelet (PLT) in Non-Hodgkin’s lymphoma (NHL) were 100% and 98%, respectively; for multiple myeloma (MM), both engraftment rates were >99%. Median times to PMN and PLT engraftments were the same between the groups demonstrating that plerixafor does not affect viability of mobilized cells or the cell’s ability to engraft.
Mozobil® (plerixafor injection) was FDA approved on Dec.15, 2008 for use in the stimulation of hematopoietic stem cells for PBSC collection in patients with MM and NHL, in combination with G-CSF. It is manufactured by Genzyme Corp. Side effects (<10%) include gastrointestinal complications and infusion site reactions. The labeling warns against anaphylaxis and splenic rupture.
Flomenberg and colleagues (2010) evaluated the safety and efficacy of plerixafor as a single agent when given subcutaneously and followed by apheresis 6 hours later for the mobilization of hematopoietic stem cells (HSC) for transplantation in 9 patients with MM. All patients mobilized enough cells for at least 1 transplant, and demonstrated prompt recovery of hematopoietic function. Median time to engraftment was 10.5 days for neutrophils and 21 days for platelets. Significant adverse events were not observed. Recovery of peripheral blood cell counts was durable in all surviving patients. Despite these successes, mobilization with plerixafor alone was modest. However, in clinical circumstances where G-CSF or chemotherapy based-mobilization should not be used, mobilization with plerixafor alone may be required and effective. The authors concluded that further research into single agent use should focus on alternate route of administration as well as adjustment of the timing of the apheresis to improve HSC yield.
Policy:
(Note: For Medicare Advantage, please refer to the Medicare Coverage Section below for coverage guidance.)
The requirements of the Horizon BCBSNJ Mozobil® (Plerixafor Injection) 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. Mozobil® (plerixafor injection) is FDA-approved for and considered medically necessary for use in combination with granulocyte colony stimulating factor (G-CSF) in mobilizing hematopoietic stem cells for the collection of peripheral blood stem cells for use in subsequent autologous transplant in patients with multiple myeloma (MM) and Non-Hodgkin’s lymphoma (NHL) if ALL of the following criteria are met:
a. Patients should not be pregnant
b. Patients should be >18 years of age
c. The prescriber is a specialist in the area of the patient’s diagnosis (e.g. oncologist) or has consulted with a specialist in the area of the patient’s diagnosis.
[INFORMATIONAL NOTE: As per the FDA approved package insert, the safety and efficacy of Mozobil (plerixafor injection) in pediatric patients have not been established in controlled clinical studies.]
II. When Mozobil® (plerixafor injection) is considered medically necessary, initial therapy will be covered up to a maximum of 4 days of therapy (one course) at the following FDA approved recommendations:
a. Mozobil® (plerixafor injection) is to be administered subcutaneously following 4 days of treatment with G-CSF and approximately 11 hours prior to apheresis (for up to 4 consecutive days).
b. The recommended dose for patients >83 kg is 0.24 mg/kg (actual body weight). The maximum dose should not exceed 40 mg/day.
c. The recommended dose for patients weighing ≤83 kg is a 20 mg dose or select dose based on 0.24 mg/kg (actual body weight) once daily.
d. In patients with renal impairment (CrCl ≤50 ml/min) a reduction in dose is needed. In patients who are ≤83 kg, a dose of 13 mg or 0.16 mg/kg once daily is recommended. In patients >83 kg a dose of 0.16 mg/kg (actual body weight) once daily is recommended. The maximum dose should not exceed 27 mg/day.
[INFORMATIONAL NOTE: In clinical trials with plerixafor, G-CSF was given SC at a dose of 10 mcg/kg/day for 4 days. On the evening of the 4th day, subjects received plerixafor 240 mcg/kg SC. The next day, after a morning dose of G-CSF, subjects underwent leukapheresis. If an inadequate number of CD34+ HSC were collected, subjects repeated with another evening dose of plerixafor, followed by a morning dose of G-CSF and leukapheresis until ≥ 5 x 106 cells/kg (NHL) or ≥ 6 x 106 cells/kg (MM) were collected or they underwent a total of 4 leukaphereses, whichever occurred first. A Phase III study by DiPersio et al. in MM patients demonstrated that 54.2%, 77.9%, 86.8%, and 86.8% of patients achieved ≥ 6 x 106 CD34+ cells/kg by apheresis day 1,2,3 and 4, respectively. A similar study in NHL patients resulted in 27.9%, 49.1%, 57.7%, and 65.6% of patients achieving ≥ 5 x 106 CD34+ cells/kg by apheresis day 1,2,3 and 4, respectively.]
[INFORMATIONAL NOTE: Leukocytosis and thrombocytopenia have been reported, monitoring CBC, including white blood cell count and platelet count is recommended by the FDA approved package insert.]
III. Mozobil® (plerixafor injection) will be approved for an additional 4-day course of treatment if ALL of the following criteria are met:
- Member continues to meet initial criteria; AND
- Absence of unacceptable toxicity from the drug (e.g. severe hypersensitivity reactions/anaphylaxis, hematologic effects (e.g. leukocytosis, thrombocytopenia); splenic enlargement/rupture, tumor cell mobilization etc.); AND
- Member has had only 1 previous treatment cycle
IV. Use of Mozobil® (plerixafor injection) beyond two courses will not be covered.
[INFORMATIONAL NOTE: Clinical trials have shown that 40% of patients who failed a first course of mobilization with plerixafor + G-CSF were able to achieve a minimum number of CD34+ HSC necessary to proceed to transplantation when treated with a second round. There is no data to demonstrate the efficacy of more than two courses of therapy in patients who have not responded.]
V. Mozobil® (plerixafor injection) is considered medically necessary for the off-label indications that are 2A or better recommendations on National Comprehensive Cancer Network (NCCN) compendium. Refer to National Comprehensive Cancer Network: Drugs and Biologics Compendium - Plerixafor. Available at: https://www.nccn.org/professionals/drug_compendium/content/.
VI. Other uses of Mozobil® (plerixafor injection) are considered investigational.
Medicare Coverage
There is no National Coverage Determination (NCD) or Local Coverage Determination (LCD) for jurisdiction JL specifically for this drug. Per Local Coverage Article. A53127 Self-Administered Drug Exclusion List, Medicare covers drugs that are furnished “incident to” a physician’s service provided that the drugs are medically reasonable and necessary, approved by the Food and Drug Administration (FDA) and are not usually administered by the patients who take them. Therefore, Medicare Advantage Products will cover Mozobil® (Plerixafor Injection) when the Horizon policy criteria is met AND the drug is furnished and administered by a licensed medical provider as part of a physician service.
Local Coverage Article A53127 Self-Administered Drug Exclusion List. Available to be accessed at Novitas Solutions, Inc., Medical Policy Search page: https://www.novitas-solutions.com/webcenter/portal/MedicareJL/LcdSearch?_afrLoop=90769712476969#!%40%40%3F_afrLoop%3D90769712476969%26centerWidth%3D100%2525%26leftWidth%3D0%2525%26rightWidth%3D0%2525%26showFooter%3Dfalse%26showHeader%3Dfalse%26_adf.ctrl-state%3D63y7eftob_46.
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:
Mozobil (Plerixafor Injection)
Plerixafor Injection (Mozobil)
References:
1. Mozobil® prescribing information. Genzyme Corporation. Cambridge, MA. May 2019.
2. Mozobil® product dossier. Genzyme Corporation. Cambridge, MA. December 2008.
3. NCCN Clinical Practice Guidelines for Multiple Myeloma.
4. NCCN Clinical Practice Guidelines for Non-Hodgkin’s Lymphoma.
5. Burger JA, Peled A. CXCR4 antagonists: targeting the microenvironment in leukemia and other cancers. Leukemia 2008. Nov 6 [Epub ahead of print]
6. Anonymous. Plerixafor: AMD 3100, AMD3100, JM 3100, SDZ SID 791. Drugs in R&D 2007;8(2):113-9.
7. Jin P, Wang E, Ren J, et al. Differentiation of two types of mobilized peripheral blood stem cells by microRNA and cDNA expression analysis. Journal of Translational Medicine 2008, 6:39.
8. Reddy GK. The Role of Plerixafor (AMD3100) in Mobilizing Hematopoietic Progenitor Cells in Patients with Hematologic Malignancies. Supportive Cancer Therapy 2006;3(2):73-76.
9. Pusic I, DiPersio JF. The Use of Growth Factors in Hematopoietic Stem Cell Transplantation. Current Pharmaceutical Design 2008;14:1950-1961.
10. Pusic I, Jiang SY, Landua S, et al. Impact of Mobilization and Remobilization Strategies on Achieving Sufficient Stem Cell Yields for Autologous Transplantation. Biol Blood Marrow Transplant 2008 Sep;14(9):1045-56.
11. Devine SM, Vij R, Rettig M, et al. Rapid mobilization of functional donor hematopoietic cells without G-CSF using AMD3100, an antagonist of the CXCR4/SDF-1 interaction. Blood 2008;112:990-998.
12. DiPersio JF, Stadtmauer EA, Nademanee AP, et al. A Phase III, Multicenter, Randomized, Double-Blind, Placebo-Controlled, Comparative of AMD3100 (Plerixafor)+G-CSF vs. G-CSF+Placebo for Mobilization in Multiple Myeloma (MM) Patients for Autologous Hematopoietic Stem Cell (aHSC) Transplantation. Blood (ASH Annual Meeting Abstracts) 2007;110(11): Abstract 445.
13. DiPersio JF, Micallef I, Stiff PJ, et al. A Phase III, Multicenter, Randomized, Double-Blind, Placebo Controlled, Comparative Trial of AMD3100 (Plerixafor)+G-CSF vs. Placebo+G-CSF in Non-Hodgkin’s Lymphoma (NHL) Patients for Autologous Hematopoietic Stem Cell (aHSC) Transplantation. Blood (ASH Annual Meeting Abstracts) 2007;110(11): Abstract 601.
14. Micallef IN, Stiff PJ, DiPersio JF, et al. Successful stem cell remobilization using plerixafor (mozobil) plus granulocyte colony-stimulating factor in patients with non-hodgkin lymphoma: results from the plerixafor NHL phase 3 study rescue protocol. Biol Blood Marrow Transplant. 2009;15(12):1578-86.
15. DiPersio JF, Micallef IN, Stiff PJ, et al. Phase III prospective randomized double-blind placebo-controlled trial of plerixafor plus granulocyte colony-stimulating factor compared with placebo plus granulocyte colony-stimulating factor for autologous stem-cell mobilization and transplantation for patients with non-Hodgkin's lymphoma. J Clin Oncol. 2009;27(28):4767-73.
16. Dugan MJ, Maziarz RT, Bensinger WI, et al. Safety and preliminary efficacy of plerixafor (Mozobil) in combination with chemotherapy and G-CSF: an open-label, multicenter, exploratory trial in patients with multiple myeloma and non-Hodgkin's lymphoma undergoing stem cell mobilization. Bone Marrow Transplant. 2010;45(1):39-47.
17. DiPersio JF, Stadtmauer EA, Nademanee A, et al. Plerixafor and G-CSF versus placebo and G-CSF to mobilize hematopoietic stem cells for autologous stem cell transplantation in patients with multiple myeloma. Blood. 2009;113(23):5720-6.
18. Giralt S, Stadtmauer EA, Harousseau JL, et al. International myeloma working group (IMWG) consensus statement and guidelines regarding the current status of stem cell collection and high-dose therapy for multiple myeloma and the role of plerixafor (AMD 3100). Leukemia. 2009;23(10):1904-12.
19. MICROMEDEX® 1.0 (Healthcare Series). DRUGDEX® Evaluations. Plerixafor. Available at: http://www.thomsonhc.com. Accessed March 1, 2020.
20. Flomenberg N, Comenzo RL, Badel K, Calandra G. Plerixafor (Mozobil) alone to mobilize hematopoietic stem cells from multiple myeloma patients for autologous transplantation. Biol Blood Marrow Transplant. 2010;16(5):695-700.
21. Chambon F, Merlin E, Rochette E, et al. Mobilization of hematopoietic stem cells by plerixafor alone in children: a sequential Bayesian trial. Transfus Apher Sci. 2013; 49(3):453-458.
22. Garcia-Escobar I, Parrilla L, Ortega LM, et al. Clinical experience with plerixafor as a mobilization regimen for autologous peripheral blood stem cell transplantation in patients with refractory germ cell tumors. Mol Clin Oncol. 2014;2(6):923-926.
23. National Comprehensive Cancer Network. NCCN Drugs & Biologics Compendium. Mozobil. Available at https://www.nccn.org/professionals/drug_compendium/content/. Accessed March 1, 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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