CurrentAetnaPolicy 0779

Plerixafor

Defines medical necessity criteria, dosing information, coding, and background evidence for plerixafor (Mozobil or generic) used to mobilize hematopoietic stem cells prior to autologous transplantation, primarily affecting clinicians and billing staff managing patients with non-Hodgkin lymphoma or multiple myeloma.

Policy Summary

PayerAetna

PolicyPlerixafor

Policy CodePolicy 0779

Change TypeNo material changes

Effective DateMar 20, 2009

Next Review DateMar 28, 2024

Key ActionObtain prior authorization and document that plerixafor will be used after G-CSF for stem cell mobilization in MM or NHL.

SourceLink

POLICY UPDATE CHANGES

No material clinical or coverage changes in this revision.

4 daysmax consecutive days

20 mg/mLvial concentration

0.24 mg/kgstandard dosing

>=2 x10^6trial target collection

CPB 0055related policy

Coverage Criteria for Plerixafor (Mozobil)

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inv-01: Initial Approval — Hematopoietic Stem Cell Mobilization — Covered when ALL of the following are met

Covered when ALL of the following are met

Initial approval criteria: The requested medication will be used to mobilize hematopoietic stem cells for collection prior to transplantation; and the requested medication will be administered after the member has received a granulocyte-colony stimulating factor (G-CSF) (e.g., filgrastim) or chemo-mobilization; and the requested medication will not be used beyond 4 consecutive days or after completion of stem cell harvest/apheresis.

inv-02: Continuation of Therapy — continuation criteria node

Continuation of plerixafor (Mozobil) injection therapy is medically necessary for all members (including new members) who meet all initial medical necessity selection criteria.

Includes member transfers/new members who meet initial criteria.

inv-03: FDA-approved indication — adults with MM or NHL — Covered when ALL of the following are met:

Covered when ALL of the following are met:

FDA-approved use: Patient is an adult with multiple myeloma (MM) or non-Hodgkin lymphoma (NHL)

Based on pivotal randomized trials demonstrating improved CD34+ yields and collection outcomes with plerixafor + G-CSF versus placebo + G-CSF (Studies 1 and 2).

Combination therapy: Plerixafor will be administered in combination with G-CSF per the approved regimen (e.g., plerixafor 0.24 mg/kg SC given the evening prior to apheresis with G-CSF 10 μg/kg daily)

Trials used G-CSF 10 μg/kg daily prior to and during apheresis; dosing and timing per FDA-approved regimen.

inv-04: Remobilization or inadequate prior mobilization (non-hematologic or pediatric reports) — Considered medically reasonable when ALL apply

Considered medically reasonable (case series and small studies) when ALL of the following apply:

Prior mobilization failure: Documented prior mobilization failure or insufficient CD34+ collection with standard mobilization (G-CSF ± chemotherapy)

Published series report successful remobilization when plerixafor is added after prior mobilization attempts.

Patient population: Patients with non-hematologic diseases requiring stem cell collection or heavily pre-treated pediatric solid tumor patients where standard mobilization failed

Evidence largely from small case series and reports; use reserved for remobilization scenarios.

inv-05: Investigational or adjunctive oncology uses — Not established/experimental

Not established/experimental — use only in clinical trials or with strong justification:

AML/ALL/CLL/CML use: Use of plerixafor to chemosensitize or to mobilize leukemic blasts in AML, ALL, CLL, or CML is investigational; preliminary studies show biological activity and mixed clinical signals, and plerixafor may mobilize malignant cells posing risk of contaminating apheresis products.

Preliminary phase I/II data exist but require validation; leukemia mobilization is contraindicated for standard harvests.

Solid tumors and other indications: Use of plerixafor as an adjunct to radiotherapy/chemoradiation (e.g., glioblastoma, cervical cancer), to treat antibody-mediated rejection, or as an antiviral based on screening studies is investigational and requires further study.

Evidence limited to early-phase trials, preclinical studies, or in-silico screens.

inv-06: Other Indications — investigational/insufficient evidence

Plerixafor use outside approved stem cell mobilization indications is described in multiple early-phase studies and preclinical reports; coverage is contingent on robust clinical evidence and is generally considered investigational.

Glioblastoma/Glioma: Preclinical data and early-phase trials suggest CXCR4 antagonism (plerixafor) can reduce tumor-associated macrophage influx after irradiation, reduce post-irradiation tumor blood flow, and may improve local tumor control; phase I studies with bevacizumab show tolerability and measurable tumor/CSF penetration but require further trials.evidence limited to preliminary studies

Light-chain (AL) Amyloidosis — HPC mobilization: Single-center series report combined G-CSF/plerixafor mobilization as safe and effective with high median CD34+ yields and low peri-mobilization morbidity; evidence requires validation in larger studies.single-center observational evidence

Lung cancer (SCLC/NSCLC): Preclinical rationale exists for targeting CXCR4 to disrupt tumor–stroma interactions and sensitize tumors to cytotoxic therapy; clinical data are limited to preclinical and review-level evidence.

Aetna considers plerixafor (Mozobil) experimental and investigational for all indications other than mobilization for autologous transplantation in non‑Hodgkin lymphoma and multiple myeloma because effectiveness for other uses has not been established.

Plerixafor is not intended for hematopoietic stem cell mobilization and harvest in patients with leukemia because it may mobilize leukemic cells and contaminate the apheresis product; this contraindication can lead to denial of coverage for leukemia indications.

Most other reported indications for plerixafor are supported only by preclinical data, early‑phase clinical reports, case series, or single‑center observational studies and therefore require further clinical trials and validation; as such they are effectively excluded from routine coverage.

Use of plerixafor for antibody‑mediated lung transplant rejection and as an antiviral for dengue or West Nile virus is not established; current reviews and screening studies identify these as emerging or hypothesis‑generating areas but provide insufficient evidence to support medical necessity.

Several indications are supported only by in‑silico analyses, preclinical models, hypothesis‑generating reports, or very small early‑phase clinical studies (for example, malaria, post‑herpetic neuralgia, and various oncology settings); these uses remain investigational and require additional validation before they can be considered medically necessary.

Coding and Billing

Other related CPT codesCPT

38205	Blood-derived hematopoietic progenitor cell harvesting for transplantation, per collection; allogeneic
38206	Blood-derived hematopoietic progenitor cell harvesting for transplantation, per collection; autologous
38230	Bone marrow harvesting for transplantation; allogeneic
38232	Bone marrow harvesting for transplantation; autologous
38240	Hematopoietic progenitor cell (HPC); allogeneic transplantation per donor
38241	Hematopoietic progenitor cell (HPC); autologous transplantation
96372	Therapeutic, prophylactic, or diagnostic injection; subcutaneous or intramuscular

Covered HCPCS Codes if selection criteria metHCPCSCovered

J2562

Injection, plerixafor, 1 mg [Mozobil]

Other related HCPCS codesHCPCS

J1442	Injection, filgrastim (G-CSF), excludes biosimilars, 1 microgram
J1447	Injection, tbo-filgrastim, 1 microgram [Granix, Neutroval]
J2505	Injection, pegfilgrastim, 6 mg
J2506	Injection, pegfilgrastim, excludes biosimilar, 0.5 mg
J2820	Injection, sargramostim (GM-CSF), 50 mcg
Q5110	Injection, filgrastim-aafi, biosimilar, (nivestym), 1 microgram
Q5111	Injection, Pegfilgrastim-cbqv, biosimilar, (udenyca), 0.5 mg

ICD-10 codes covered if selection criteria are metICD-10Covered

C82.00
C82.99
C83.00 - C83.99	Lymphosarcoma and related malignant tumors of lymphatic tissue
C84.00 - C84.99	Other malignant neoplasms of lymphoid and histiocytic tissue
C88.4
C88.8 - C90.32	Malignant immunoproliferative diseases and multiple myeloma
C91.40 - C91.42
C96.0 - C96.9

ICD-10 codes not covered for CPB-listed indications (experimental/non-covered)ICD-10Not Covered

A90	Dengue fever
A91	Dengue hemorrhagic fever
A92.30 - A92.39	West Nile virus infection
C33 - C34	Malignant neoplasm of trachea, bronchus, and lung
C53.0 - C53.9	Malignant neoplasm of cervix uteri
C71.0 - C71.9	Malignant neoplasm of brain [glioma]
C91.00 - C91.02	Acute lymphoblastic leukemia [ALL]
D57.00 - D57.819	Sickle-cell disorders
D70.0 - D70.9	Neutropenia [treatment or prophylaxis]

inv-17: Minimum pre-apheresis peripheral blood CD34+ count for successful day 1 collection

Minimum pre-apheresis PB CD34+20 cells/µL (minimum threshold correlated with successful day‑1 collection)

Source contextDerived from Pusic et al. analysis correlating pre‑apheresis PB CD34+ with first‑day apheresis yield

Clinical implicationPre‑apheresis PB CD34+ <20 cells/µL predicts low likelihood of successful day‑1 collection and may prompt remobilization strategies

inv-18: CD34+ collection thresholds — examples cited

Common collection targets≥2 x10^6 CD34+ cells/kg is a common minimum success threshold used in observational series and trials

Higher trial targets (NHL)Study 1: ≥5 x10^6 CD34+ cells/kg collected within ≤4 aphereses (59% with plerixafor+G‑CSF vs 20% with placebo+G‑CSF)

Higher trial targets (MM)Study 2: ≥6 x10^6 CD34+ cells/kg collected within ≤2 aphereses (72% with plerixafor+G‑CSF vs 34% with placebo+G‑CSF)

Remobilization series exampleNon‑hematologic remobilization series: 85% achieved ≥2 x10^6 CD34+/kg after plerixafor+G‑CSF

Provider Responsibilities, Prior Authorization, and Documentation

Prior Authorization

Prior Authorization Required

Prior authorization is required for HCPCS J2562 (plerixafor, 1 mg) and associated injection/procedure codes when used for hematopoietic progenitor cell (HPC) mobilization prior to transplantation. Follow Aetna prior authorization processes and submit requests before therapy initiation.

Affected code: J2562 (Injection, plerixafor, 1 mg)
Related administration codes: 96372; harvest CPTs 38205, 38206, 38230, 38232, 38240, 38241
Policy reviewed: 01/09/2024; Effective: 03/20/2009

Prior Authorization

Prior Authorization for plerixafor (Mozobil)

Plerixafor (Mozobil) is FDA-approved for use in combination with G-CSF for mobilization of hematopoietic stem cells in adults with multiple myeloma (MM) or non-Hodgkin lymphoma (NHL). Prior authorization should document the indication and planned use with G-CSF per the FDA regimen.

FDA indication: adults with MM or NHL in combination with G-CSF (Genzyme PI)
Document that plerixafor will be given per approved regimen (e.g., evening doses after G-CSF)
Evidence: phase 3 trials demonstrating improved CD34+ collection with plerixafor + G-CSF

Note

Plerixafor for HPC Mobilization (Amyloidosis)

Plerixafor plus G-CSF has been used for HPC mobilization in light chain (AL) amyloidosis and reported as safe and effective in cohort studies; include this context in authorization requests when mobilization is for AL amyloidosis prior to transplant.

AL amyloidosis data: cohort of 53 patients with good collection yields and acceptable toxicity (Badar et al., 2019)
These findings require validation in larger controlled studies but may support individual clinical justification

Documentation Required

G-CSF or Chemo-mobilization Prerequisite

Plerixafor must be administered after the member has received G-CSF or chemo-mobilization prior to authorization; requests should state prior mobilization regimen and timing relative to planned plerixafor dosing.

Prerequisite: G-CSF (e.g., filgrastim) or chemo-mobilization completed before plerixafor per policy criteria
Typical regimen: G-CSF daily for 4 days prior to first plerixafor dose (per FDA studies)

Step Therapy

Step Therapy Context

Step therapy context: evidence supports plerixafor plus G-CSF, particularly for patients who fail initial mobilization with G-CSF ± chemotherapy. No explicit step-therapy sequence is defined in this policy, but prior mobilization attempts and rationale should be documented.

Studies show lower failure rates with G-CSF + plerixafor versus G-CSF alone
Document prior mobilization attempts (dates, regimens, and outcomes) when applicable
No formal step sequence mandated by policy

Note

Mobilization Alternative in SCD

Plerixafor has been explored as an alternative mobilization strategy in sickle cell disease (SCD) due to the vaso-occlusive risk associated with G-CSF; include this consideration and any relevant trial identifiers in authorization notes.

Preclinical and early clinical data suggest plerixafor may mobilize HPCs without vaso-occlusion seen with G-CSF
Clinical trials in SCD (e.g., NCT02193191) are ongoing — use in SCD should be justified with supporting data

Documentation Required

Required Clinical Documentation

Required clinical documentation: Prior authorization requests must include indication (MM, NHL, or specific off-label justification such as AL amyloidosis), planned combination with G-CSF per regimen, prior mobilization attempts and outcomes, and intended dosing schedule for harvest.

Indication and transplant intent (mobilization for collection prior to transplantation)
Confirmation that G-CSF or chemo-mobilization was given prior to plerixafor
Details of prior mobilization failures (if any) including CD34+ yields and dates
Planned plerixafor dosing schedule and duration (not to exceed 4 consecutive days or beyond completion of harvest)

Documentation Required

Trial Dosing and Pharmacokinetic Documentation

Trial dosing and pharmacokinetic documentation: clinical trial regimens and pharmacokinetic data (e.g., 0.24 mg/kg evening dosing in phase 3 trials; PK/CSF/tissue levels in early glioma studies) may be referenced to support dosing rationale — include trial details when relevant.

Phase 3 studies used plerixafor 0.24 mg/kg given each evening prior to apheresis after G-CSF priming
Early-phase glioma studies report higher dose ranges (example: 320 µg/kg) with PK sampling — include such data only when supporting investigational use

Documentation Required

References to Prescribing Information and Clinical Guidelines

References that should be included or cited in authorization/supporting documentation: Genzyme (Mozobil) prescribing information, NCCN Drugs & Biologics Compendium, HCT and IMWG guidelines, and key clinical studies showing efficacy of plerixafor + G-CSF.

Genzyme Corporation. Mozobil (plerixafor) Prescribing Information (latest revision)
NCCN Drugs & Biologics Compendium — Plerixafor (January 2023)
IMWG and HCT consensus/guidelines and pivotal clinical trials (Pusic 2008; Genzyme Phase 3 studies)

Denial Risk

Indication-Based Denial Risk, Investigational Use, and Contraindication (Leukemia)

Indication-based denial risk and investigational use: Requests for indications other than mobilization prior to transplantation (or indications listed as appropriate in policy) are subject to denial as experimental/investigational. Use in leukemia is contraindicated due to risk of mobilizing leukemic cells and potential contamination of the apheresis product.

Experimental/Investigational indications include leukemia, many solid tumors, SCD (outside trial context), and others listed in the policy
Contraindication: leukemia — plerixafor may mobilize leukemic cells and is not intended for HSC mobilization in leukemia patients
Policy denials may be issued when requested use is outside approved/medically necessary criteria

Note

No Explicit Denial Triggers Stated

Administrative note: The policy does not list explicit single denial triggers beyond the stated coverage criteria; Clinical Policy Bulletins (CPBs) do not guarantee coverage. Adjudication follows standard Aetna medical necessity review processes.

No explicit additional denial triggers are specified in this CPB
Coverage determinations are made case-by-case and prior authorization approval does not guarantee payment

Dosing Regimens and Supported Combinations

Regimen	Indication / Setting	Timing / Notes	Coverage status
Plerixafor 0.24 mg/kg subcutaneously (given evening prior to apheresis) plus G-CSF (e.g., G-CSF 10 µg/kg daily)
Stem cell mobilization for autologous transplantation in adults with multiple myeloma (MM) or non-Hodgkin lymphoma (NHL)
Plerixafor administered each evening prior to planned apheresis after daily G-CSF for at least 4 days; dosing and schedule per pivotal trials (approximately 11 hours prior to apheresis)
Covered

Regimen	Indication / Setting	Timing / Notes	Coverage status
Single‑agent plerixafor (subcutaneous) with apheresis performed ~4–6 hours after dose
Investigational mobilization approach for patients where G-CSF/chemomobilization is contraindicated or in pediatric/solid tumor contexts (case series and small studies)
Small series used single‑agent subcutaneous plerixafor followed by apheresis 6 hours later; further study recommended to optimize route, timing, and yield
Experimental

Regimen	Indication / Setting	Timing / Notes	Coverage status
Plerixafor 320 µg/kg subcutaneously on days 1–21 plus bevacizumab 10 mg/kg IV on days 1 and 15 of each 28‑day cycle
Phase I dose‑escalation regimen evaluated in recurrent high‑grade glioma (recurrent HGG) patients
Part 1 used a 3x3 escalation to a maximum tolerated dose (plerixafor 320 µg/kg days 1–21); plasma, CSF and tumor penetration assessed; no DLTs at MTD reported
Experimental

Regimen	Indication / Setting	Timing / Notes	Coverage status
Plerixafor administered in combination with G‑CSF and/or added to regimens containing bortezomib and cyclophosphamide
Used in difficult‑to‑mobilize patients, including dialysis‑dependent multiple myeloma and other case‑series populations where prior mobilization yielded low CD34+ counts
Case reports/series describe adding plerixafor to prior regimens (e.g., bortezomib + cyclophosphamide) to markedly increase CD34+ yields (one report noted a 6‑fold increase); evidence is limited to small observational reports
Experimental

Definitions

inv-36: Mobilization — definition of moving HSCs from bone marrow into peripheral blood for collection

DefinitionMobilization: the process of moving hematopoietic stem cells (HSCs) from bone marrow into peripheral blood for collection (apheresis), commonly using G‑CSF and agents like plerixafor)

Typical use casePerformed prior to autologous transplantation to obtain peripheral blood stem cells for infusion

Relation to CXCR4/CXCL12Mobilization strategies often target CXCR4/CXCL12 interactions to release HSCs from marrow niches

inv-37: Plerixafor (Mozobil) — CXCR4 antagonist mechanism summary

Mechanism summaryPlerixafor (Mozobil) is a CXCR4 chemokine receptor antagonist that blocks binding of SDF‑1α (CXCL12) to CXCR4, disrupting marrow anchoring of HSCs and facilitating mobilization into peripheral blood

Indication noteApproved in combination with G‑CSF for mobilization of HSCs in MM and NHL (FDA; Genzyme prescribing information)

Safety considerationsPrescribing information lists warnings including tumor cell mobilization in leukemia, hypersensitivity, splenic rupture, and hematologic effects

inv-38: Successful mobilization — definition and common CD34+ thresholds (e.g., >=2 x10^6 CD34+ cells/kg)

Definition of successful mobilizationAchievement of a target CD34+ cell dose for transplantation (commonly ≥2 x10^6 CD34+ cells/kg); trials have used higher targets such as ≥5 or ≥6 x10^6 CD34+ cells/kg depending on graft goals)

Operational benchmarksPhase 3 studies reported proportions reaching ≥5 x10^6/kg (NHL) or ≥6 x10^6/kg (MM) within limited aphereses when using plerixafor+G‑CSF

Clinical relevanceSuccessful mobilization correlates with timely engraftment; pre‑apheresis PB CD34+ and achieved/kg dose guide adequacy for transplant

inv-39: MERT — concept reference related to SDF-1/CXCR4 pathway modulation

ConceptMERT (macrophage exclusion after radiation therapy): strategy to enhance tumor response and protect normal tissue by blocking TAM accumulation via the SDF‑1/CXCR4 pathway

Relation to CXCR4 antagonismPreclinical and early clinical data suggest CXCR4 blockade (e.g., plerixafor) can prevent post‑irradiation TAM influx and improve local tumor control

Evidence statusPreliminary findings require validation in well‑designed clinical trials

inv-40: WHIM syndrome — rare congenital CXCR4 gain-of-function syndrome definition

DefinitionWHIM syndrome: rare congenital immunodeficiency caused by autosomal dominant gain‑of‑function CXCR4 mutations (warts, hypogammaglobulinemia, infections, myelokathexis)

PathophysiologyCXCR4 carboxy‑terminus truncation leads to neutropenia and retention of neutrophils in marrow (myelokathexis)

Plerixafor relevanceSmall studies show plerixafor can mobilize leukocytes and correct neutropenia in WHIM at low intermittent doses with favorable tolerability

inv-41: Plerixafor (Mozobil) — prescribing information citation (Genzyme, revised Aug 2020)

Prescribing informationGenzyme Corporation. Mozobil (plerixafor) injection, prescribing information; revised August 2020

Regulatory statusMozobil is indicated with G‑CSF for mobilization of HSCs for autologous transplantation in MM and NHL

Key safety warningsPI includes warnings: tumor cell mobilization in leukemia, hypersensitivity/anaphylaxis, splenic rupture, hematologic effects; common adverse reactions listed

OpenPayer

Plerixafor

Coverage Criteria for Plerixafor (Mozobil)

Coding and Billing

Provider Responsibilities, Prior Authorization, and Documentation

Dosing Regimens and Supported Combinations

Line of Therapy Context

Biomarker and Laboratory Thresholds

Definitions

Background and Evidence Summary

Revision History