Pending Policies - Prescription Drugs


Plerixafor Injection (Mozobil)

Number:RX501.071

Effective Date:03-15-2018

Coverage:

*CAREFULLY CHECK STATE REGULATIONS AND/OR THE MEMBER CONTRACT*

Medical policies are a set of written guidelines that support current standards of practice. They are based on current peer-reviewed scientific literature. A requested therapy must be proven effective for the relevant diagnosis or procedure. For drug therapy, the proposed dose, frequency and duration of therapy must be consistent with recommendations in at least one authoritative source. This medical policy is supported by FDA-approved labeling and nationally recognized authoritative references. These references include, but are not limited to: MCG care guidelines, DrugDex (IIb level of evidence or higher), NCCN Guidelines (IIb level of evidence or higher), NCCN Compendia (IIb level of evidence or higher), professional society guidelines, and CMS coverage policy.

When the requested chemotherapeutic agent is being utilized in a regimen in combination with other chemotherapeutic agents, the entire regimen (including dose, frequency, and duration) must be consistent with recommendations in at least one authoritative source, including but not limited to FDA labeling and nationally recognized compendia or clinical guidelines such as National Comprehensive Cancer Network (NCCN) and CMS coverage policy. HCSC may require a provider to submit documentation from nationally recognized compendia, clinical guidelines, or active Phase III clinical trials supporting the requested regimen.

Plerixafor injection (Mozobil™), when given in conjunction with a granulocyte-colony stimulating factor (G-CSF) in preparation for autologous stem cell harvesting, may be considered medically necessary for the following indications:

Non-Hodgkin’s lymphoma (NHL), and

Multiple myeloma (MM).

All other use of plerixafor injection (Mozobil™) is considered experimental, investigational and/or unproven, including but not limited to the treatment of:

Acute myeloid leukemia,

Germ cell tumors,

Hodgkin’s disease,

Liver failure, acute,

Lung cancer,

Neuroblastoma, metastatic,

Testicular cancer,

Thalassemia major, or

WHIM (warts, hypogammaglobulinemia, infections, and myelokathexis) syndrome.

Description:

On December 15, 2008, the U.S. Food and Drug Administration (FDA) approved plerixafor injection (Mozobil™) as an orphan drug to mobilize or increase the number of hematopoietic stem-cells within the peripheral blood required for collection and subsequent autologous stem-cell infusion following ablative therapy, for the treatment of non-Hodgkin’s lymphoma (NHL) and multiple myeloma (MM). Plerixafor is given in conjunction with a granulocyte-colony stimulating factor (G-CSF). (1, 2, 6, 7) It is manufactured by Genzyme Corporation, Cambridge, Massachusetts. (1)

An orphan drug (orphan product designation [OPD]) is defined in the 1984 amendments of the Orphan Drug Act as "a drug intended to treat a condition affecting fewer than 200,000 persons in the United States or will not recover development cost, plus a reasonable profit, within seven years following FDA approval. The Orphan Drug Act was signed into law on January 4, 1983."

Rationale:

This medical policy was created in 2010 and has been updated with a literature review through January 10, 2018. The following is a summary of the key literature to date.

The efficacy and safety of plerixafor in combination with granulocyte-colony stimulating factor (G-CSF) in non-Hodgkin’s lymphoma (NHL) and multiple myeloma (MM) were evaluated in two placebo-controlled studies (Studies 1 and 2). Patients were randomized to receive either plerixafor 0.24 mg/kg or placebo each evening prior to apheresis. All patients received G-CSF 10 micrograms/kg daily for four-days prior to the first dose of plerixafor or placebo and prior to apheresis. Results from 298 patients with NHL from Study 1 and 302 patients with MM from Study 2 were analyzed. The U.S. Food and Drug Administration (FDA) orphan product designation (OPD) was based upon these two studies. (1, 3, 6)

In Study 1, 59% of patients with NHL who were mobilized with plerixafor and G-CSF collected > 5 X 106 CD34+ cells/kg from the peripheral blood in four or fewer apheresis sessions compared with 20% of patients who were mobilized with placebo and G-CSF (p < 0.001). The median number of days to reach > 5 x 106 CD34+ cells/kg was three-days for the plerixafor group and not evaluable for the placebo group. (1, 3, 4)

In Study 2, 72% of patients with MM who were mobilized with plerixafor and G-CSF collected > 6 X 106 CD34+ cells/kg from the peripheral blood in two or fewer apheresis sessions compared with 34% of patients who were mobilized with placebo and G-CSF (p <0.001). The median number of days to reach > 6 x 106 CD34+ cells/kg was one-day for the plerixafor group and four-days for the placebo group. (1, 3, 4)

Safety data for plerixafor in combination with G-CSF were obtained from 983 patients enrolled in 16 clinical studies (593 patients enrolled in randomized Studies 1 and 2 plus 410 patients enrolled in 14 additional non-randomized studies). Patients were primarily treated with plerixafor at daily doses of 0.24 mg/kg subcutaneously. Median exposure to plerixafor was two-days (range 1 to 7 days). (1)

Clinical trials are currently being conducted in the United States to determine the efficacy of plerixafor for the mobilization of stem-cells to treat other types of condition, including but not limited to, acute myeloid leukemia, germ cell tumors, Hodgkin’s disease, acute liver failure, lung cancer, metastatic neuroblastoma, testicular cancer, thalassemia major, or WHIM (wars, hypogammaglobulinemia, infections, and myelokathexis) syndrome. (5, 8-20)

Practice Guidelines and Position Statements

National Comprehensive Cancer Network (NCCN) Drugs & Biologics Compendium®

Used in hematopoietic cell transplant for the following (21):

• Mobilization of hematopoietic progenitor cells in combination with filgrastim, filgrastim-sndz, or tbo-filgrastim in the autologous setting in select patients with non-Hodgkin's lymphoma or multiple myeloma (2A Recommendations),

• Mobilization of donor hematopoietic progenitor cells in the allogeneic setting (2B Recommendations).

NCCN Guidelines

The NCCN guidelines (V.2.2017) on Myeloid Growth Factors in Mobilization and Post Hematopoietic Cell Transplant make the following recommendations (22):

Mobilization of Hematopoietic Progenitor Cells in Autologous Setting – 2A Recommendations

Filgrastim/filgrastim-sndz/tbo-filgrastim + plerixafor (for selected patients with non-Hodgkin’s lymphoma or multiple myeloma)

o Plerixafor is indicated for:

1.  Patients who were heavily pre-treated or had prior treatment with >10 cycles of cytotoxic chemotherapy, or those who have failed prior collection attempts or exhibit risk factors for being poor mobilizers due to more than 6 cycles of lenalidomide or fludarabine, or radiation to the pelvis.

2.  As “just in time” or “rescue” in the case of suboptimal peripheral CD34+ count.

o Dosing:

1.  Filgrastim/filgrastim-sndz/tbo-filgrastim dose: 10 mcg/kg/d X 4 days. On the evening of day 4, start plerixafor by SC injection 11 hours prior to day 5 collection (the next morning).

2.  Plerixafor dose: 0.24 mg/kg/d for patients weighing >83 kg; 20 mg (fixed dose), or 0.24 mg/kg/d for patients weighing >83 kg, maximum 4 doses (if creatinine clearance >50 mL/min, maximum dose 50 mg/d)

Mobilization of Allogeneic Donors – 2B Recommendations

Allogeneic Hematopoietic Donors:

o Filgrastim (preferred) or filgrastim-sndz (category 2B) or tbo-filgrastim.

1.  Dose: 10 mcg/kg/d by SC injection, start collection on day 4 or 5.

o Plerixafor (category 2B): Use in normal donors is under study.

Contract:

Each benefit plan, summary plan description or contract defines which services are covered, which services are excluded, and which services are subject to dollar caps or other limitations, conditions or exclusions. Members and their providers have the responsibility for consulting the member's benefit plan, summary plan description or contract to determine if there are any exclusions or other benefit limitations applicable to this service or supply. If there is a discrepancy between a Medical Policy and a member's benefit plan, summary plan description or contract, the benefit plan, summary plan description or contract will govern.

Coding:

CODING:

Disclaimer for coding information on Medical Policies

Procedure and diagnosis codes on Medical Policy documents are included only as a general reference tool for each policy. They may not be all-inclusive.

The presence or absence of procedure, service, supply, device or diagnosis codes in a Medical Policy document has no relevance for determination of benefit coverage for members or reimbursement for providers. Only the written coverage position in a medical policy should be used for such determinations.

Benefit coverage determinations based on written Medical Policy coverage positions must include review of the member’s benefit contract or Summary Plan Description (SPD) for defined coverage vs. non-coverage, benefit exclusions, and benefit limitations such as dollar or duration caps.

CPT/HCPCS/ICD-9/ICD-10 Codes

The following codes may be applicable to this Medical policy and may not be all inclusive.

CPT Codes

None

HCPCS Codes

J2562

ICD-9 Diagnosis Codes

Refer to the ICD-9-CM manual

ICD-9 Procedure Codes

Refer to the ICD-9-CM manual

ICD-10 Diagnosis Codes

Refer to the ICD-10-CM manual

ICD-10 Procedure Codes

Refer to the ICD-10-CM manual


Medicare Coverage:

The information contained in this section is for informational purposes only.  HCSC makes no representation as to the accuracy of this information. It is not to be used for claims adjudication for HCSC Plans.

The Centers for Medicare and Medicaid Services (CMS) does not have a national Medicare coverage position. Coverage may be subject to local carrier discretion.

A national coverage position for Medicare may have been developed since this medical policy document was written. See Medicare's National Coverage at <http://www.cms.hhs.gov>.

References:

1. FDA – Mozobil (plerixafor injection) - Drugs@FDA: FDA Approved Drug Products. Food and Drug Administration. Available at <https://www.accessdata.fda.gov> (accessed - 2018 January 3).

2. Wagstaff AJ. Plerixafor: in patients with non-Hodgkin’s lymphoma or multiple myeloma. Drugs. 2009; 69(3):319-26. PMID 19275275

3. Stiff P, Micallef I, McCarthy P, et al. Treatment of plerixafor in non-Hodgkin’s lymphoma and multiple myeloma patients to increase the number of peripheral blood stem cells when given a mobilizing regimen of G-CSF: implications for the heavily pretreated patient. Biol Blood Marrow Transplant. Feb 2009; 15(2):249-56. PMID 19167685

4. 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. Jun 4 2009; 113(23):5720-6. PMID 19363221

5. Burger JA, and DJ Stewart. CXCR4 chemokine receptor antagonists: perspectives in SCLC. Expert Opin Investig Drugs. Apr 2009; 18(4):481-90. PMID 193335276

6. Brave M, Farrell A, Ching Lin S, et al. FDA review summary: Mozobil in combination with granulocyte colony-stimulating factor to mobilize hematopoietic stem cells to the peripheral blood for collection and subsequent autologous transplantation. Oncology. 2010; 78(3-4):282-8. PMID 20530974

7. Basak GW, Knopinska-Posluszny W, Matuszak M, et al. Hematopoietic stem cell mobilization with the reversible CXCR4 receptor inhibitor plerixafor (AMD3100) – Polish compassionate use experience. Ann Hematol. May 2011; 90(5):557-68. PMID 20938660

8. Saure C, Wigelt C, Schroeder T, et al. Plerixafor enables successful hematopoietic stem cell collection in an extensively pretreated patient with testicular cancer. Acta Haematol. 2010; 124(4):235-8. PMID 21099212

9. Tuffaha H, and FA Abdel-Rahman. Successful stem-cell mobilization and transplantation using plerixafor in a patient with a germ cell tumor. Hematol Oncol Stem Cell Ther. 2010; 3(4):203-5. PMID 21150242

10. Mark AL, Sun Z, Warren DS, et al. Stem cell mobilization is lifesaving in an animal model of acute liver failure. Ann Surg. Oct 2010; 252(4):591-6. PMID 20881764

11. Wesson RN and AM Cameron. Stem cells in acute liver failure. Adv Surg. 2011; 45:117-30. PMID 21954682

12. Heckman D, Laufs S, Maier P, et al. A Lentiviral CXCR4 overexpression and knockdown model in colorectal cancer cell lines reveals plerixafor-dependent suppression of SDF-induced migration and invasion. Onkologie. 2011; 34(10):502-8. PMID 21985848

13. Burger JA, Stewart DJ, Wald O, et al. Potential of CXCR4 antagonists for the treatment of metastatic lung cancer. Expert Rev AntiCancer Ther. Apr 2011; 11(4):621-30. PMID 21504328

14. Worel N, Rosskopf K, Neumeister P, et al. Plerixafor and granulocyte-colony-stimulating factor (G-CSF) in patients with lymphoma and multiple myeloma previously failing mobilization with G-CSF with or without chemotherapy for autologous hematopoietic stem cell mobilization: the Austrian experience on a named patient program. Transfusion. May 2011; 51(5):968-75. PMID 20880037

15. Kobold S, Isernhagen J, Hübel K, et al. Plerixafor is effective and safe for stem cell mobilization in heavily pretreated germ cell tumor patients. Bone Marrow Transplant. Aug 2011; 46(8):1053-6. PMID 21102500

16. McDermott DH, Liu Q, Ulrick J, et al. The CXCR4 antagonist plerixafor corrects panleukopenia in patients with WHIM syndrome. Blood. Nov 3 2011; 118(18):4957-62. PMID 21890643

17. Dale DC, Boylard AA, Kelley ML, et al. The CXCR4 antagonist plerixafor is a potential therapy for myelokathexis, WHIM syndrome. Blood. Nov 3 2011; 118(18):4963-6. PMID 21835955

18. Yannaki E, Papayannopoulou T, Jonlin E, et al. Hematopoietic stem cell mobilization for gene therapy of adult patients with severe thalassemia: results from clinical trials using G-CSF or plerixafor in splenectomized and non-splenectomized subjects. Mol Ther. Jan 2012; 20(1):230-8. PMID 21952171

19. Modak S, Cheung IY, Kushner BH, et al. Plerixafor plus granulocyte-colony stimulating factor for autologous hematopoietic stem cell mobilization in patients with metastatic neuroblastoma. Pediatr Blood Cancer. Mar 2012; 58(3):469-71. PMID 21416584

20. Uy GL, Rettig MP, Motabi IH, et al. A phase ½ study of chemosensitization with the CXCR4 antagonist plerixafor in relapsed or refractory acute myeloid leukemia. Blood. Apr 26 2012; 119(17):3917-24. PMID 22308295

21. NCCN – Plerixafor (2018). National Comprehensive Cancer Network Drugs & Biologics Compendium®. Available at <http://www.nccn.org> (accessed - 2018 January 3).

22. NCCN – Myeloid Growth Factors Version 2.2017 (October 13, 2017). National Comprehensive Cancer Network Clinical Practice Guidelines in Oncology (NCCN Guideline). Available at <http://www.nccn.org> (accessed - 2017 November 27).

Policy History:

Date Reason
3/15/2018 Document updated with literature review. Coverage unchanged.
8/1/2016 Reviewed. No changes.
2/15/2015 Document updated with literature review. Coverage unchanged.
11/15/2012 Document updated with literature review. The following was added: Treatment using Mozobil for acute myeloid leukemia, germ cell tumors, Hodgkin’s disease, acute liver failure, lung cancer, metastatic neuroblastoma, testicular cancer, thalassemia major, or WHIM (warts, hypogammaglobulinemia, infections, and myelokathexis) syndrome is considered experimental, investigational and unproven.
1/1/2010 New medical document. Plerixafor injection (Mozobil ™) may be considered medically necessary when criteria are met.

Archived Document(s):

Title:Effective Date:End Date:
Plerixafor Injection (Mozobil)03-15-201803-14-2020
Plerixafor Injection (Mozobil)08-01-201603-14-2018
Plerixafor Injection (Mozobil)02-15-201507-31-2016
Plerixafor Injection (Mozobil)11-15-201202-14-2015
Plerixafor Injection (Mozobil)01-01-201011-14-2012
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