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This medical policy (medical coverage guideline) is Copyright 2017, Blue Cross and Blue Shield of Florida (BCBSF). All Rights Reserved. You may not copy or use this document or disclose its contents without the express written permission of BCBSF. The medical codes referenced in this document may be proprietary and owned by others. BCBSF makes no claim of ownership of such codes. Our use of such codes in this document is for explanation and guidance and should not be construed as a license for their use by you. Before utilizing the codes, please be sure that to the extent required, you have secured any appropriate licenses for such use. Current Procedural Terminology (CPT) is copyright 2017 American Medical Association. All Rights Reserved. No fee schedules, basic units, relative values, or related listings are included in CPT. The AMA assumes no liability for the data contained herein. Applicable FARS/DFARS restrictions apply to government use. CPT® is a trademark of the American Medical Association. The use of specific product names is illustrative only. It is not intended to be a recommendation of one product over another, and is not intended to represent a complete listing of all products available.

09-J1000-95

Original Effective Date: 06/15/13

Reviewed: 06/14/17

Revised: 11/15/17

Next Review: 06/13/18

Subject: Pomalidomide (Pomalyst®) Capsule

THIS MEDICAL COVERAGE GUIDELINE IS NOT AN AUTHORIZATION, CERTIFICATION, EXPLANATION OF BENEFITS, OR A GUARANTEE OF PAYMENT, NOR DOES IT SUBSTITUTE FOR OR CONSTITUTE MEDICAL ADVICE. ALL MEDICAL DECISIONS ARE SOLELY THE RESPONSIBILITY OF THE PATIENT AND PHYSICIAN. BENEFITS ARE DETERMINED BY THE GROUP CONTRACT, MEMBER BENEFIT BOOKLET, AND/OR INDIVIDUAL SUBSCRIBER CERTIFICATE IN EFFECT AT THE TIME SERVICES WERE RENDERED. THIS MEDICAL COVERAGE GUIDELINE APPLIES TO ALL LINES OF BUSINESS UNLESS OTHERWISE NOTED IN THE PROGRAM EXCEPTIONS SECTION.

           

Position Statement

Dosage/ Administration

Billing/Coding

Reimbursement

Program Exceptions

Definitions

           

Related Guidelines

Other

References

Updates

 

Previous Version

           

DESCRIPTION:

Pomalidomide (Pomalyst), a thalidomide analogue, was approved by the US Food and Drug Administration (FDA) in February 2013 for treatment of multiple myeloma (MM) in persons who have received at least two prior therapies, including lenalidomide (Revlimid) and bortezomib (Velcade), and have demonstrated disease progression on or within 60 days of completion of last therapy. Pomalyst was previously granted orphan designation by the FDA for the treatment of MM in 2003. The approved indication was expanded in April 2015 to allow one of the prior therapies to be any proteasome inhibitor [e.g., bortezomib (Velcade), carfilzomib (Kyprolis), or ixazomib (Ninlaro)]. Although the mechanism by which pomalidomide exerts its cytotoxic activity has not been fully elucidated, it is thought to inhibit the proliferation of hematopoietic tumor cells and induce apoptosis. In clinical trials, pomalidomide inhibited proliferation of MM cell lines that were resistant to lenalidomide.

Multiple myeloma is a malignant neoplasm of plasma cells that accumulate in bone marrow, leading to bone destruction and marrow failure. Although MM is typically sensitive to a variety of cytotoxic drugs, both as initial treatment or as treatment of relapsed disease, the durability of the response is transient and a cure for MM remains elusive. Persons diagnosed with MM are classified as either having smoldering (asymptomatic) disease or active (symptomatic) disease. Those classified with active MM are initially treated with primary therapy and in select cases primary therapy is followed by high-dose chemotherapy with stem cell transplant (SCT). Therapy for previously treated MM will eventually be required for persons with relapsed disease after allogeneic or autologous SCT, primary progressive disease after initial allogeneic or autologous SCT, or persons who are non-transplant candidates who have progressive or relapsing disease after primary therapy.

As therapy for previously treated MM, the National Comprehensive Cancer Network (NCCN) Guidelines for MM (Version 1.2018) list the following six pomalidomide-containing regimens under “Other Recommended Regimens”: pomalidomide + dexamethasone (category 1 recommendation), pomalidomide + bortezomib + dexamethasone (category 2A), pomalidomide + carfilzomib + dexamethasone (category 2A), pomalidomide + cyclophosphamide + dexamethasone (category 2A), ixazomib + pomalidomide + dexamethasone (category 2A), and daratumumab (Darzalex) + pomalidomide + dexamethasone (category 2A). There is a footnote stating single-agent pomalidomide can be considered for steroid-intolerant individuals. All of the listed regimens also include a footnote stating, “Indicated for the treatment of patients who have received at least two prior therapies including an immunomodulatory agent and a proteasome inhibitor and who have demonstrated disease progression on or within 60 days of completion of the last therapy.” The NCCN also supports the use of pomalidomide + dexamethasone as a Category 2A recommendation for the treatment relapsed/refractory systemic light chain amyloidosis (Version 1.2018).

POSITION STATEMENT:

Comparative Effectiveness

The Food and Drug Administration has deemed the drug(s) or biological product(s) in this coverage policy to be appropriate for self-administration or administration by a caregiver (i.e., not a healthcare professional). Therefore, coverage (i.e., administration) in a provider-administered setting such as an outpatient hospital, ambulatory surgical suite, physician office, or emergency facility is not considered medically necessary.

Initiation of pomalidomide (Pomalyst) meets the definition of medical necessity for treatment of EITHER of the following indications (“1” or “2) when ALL of the associated criteria are met:

1. Relapsed/refractory multiple myeloma (MM) when ALL of the following criteria are met (“a” to “g”):

a. Member has received at least TWO prior therapies including an immunomodulatory agent (e.g., lenalidomide, thalidomide) AND a proteasome inhibitor (e.g., bortezomib, ixazomib)

b. The member’s MM is refractory (i.e., disease progression on treatment, or progression within 60 days after the last dose of their most recent therapy)

c. ANY of the following drug regimens will be used (“i”, “ii”, “iii”, “iv”, “v”, “vi”, or “vii”):

i. Pomalidomide will be used as triplet therapy in combination with both bortezomib + dexamethasone

ii. Pomalidomide will be used as triplet therapy in combination with both carfilzomib + dexamethasone

iii. Pomalidomide will be used as triplet therapy in combination with both cyclophosphamide + dexamethasone

iv. Pomalidomide will be used as triplet therapy in combination with both ixazomib + dexamethasone

v. Pomalidomide will be used as triplet therapy in combination with both daratumumab + dexamethasone

vi. Pomalidomide will be used as doublet therapy in combination with dexamethasone

vii. Pomalidomide will be used as monotherapy (if the member is steroid-intolerant)

d. The member’s MM was NOT previously refractory (i.e., disease progression on treatment, or progression within 60 days after the last dose of a given therapy) to a pomalidomide-containing treatment regimen

e. Pomalidomide will NOT be used in combination with another immunomodulatory agent (i.e., thalidomide or lenalidomide)

f. Laboratory documentation of the member’s baseline (i.e., within 60 days prior to initiating treatment with pomalidomide) serum monoclonal protein (M-protein) as detected by serum protein electrophoresis (SPEP) is provided*

*If the M-protein is undetectable by SPEP, documentation of a baseline serum free light chain assay (SFLCA) must also be provided

g. The dosage does not exceed 4 mg daily for 21 days of a 28-day cycle and will be obtained using the fewest number of capsules possible.

2. Relapsed/refractory systemic light chain amyloidosis (SLCA) when ALL of the following criteria are met:

a. The diagnosis has been validated by confirming the presence of amyloid deposits in tissue AND the deposits are composed of light chains

b. Member has received one or more prior lines of NCCN-recommended therapy for their for their disease

c. Pomalidomide will be used in combination with dexamethasone

d. Laboratory documentation of the member’s baseline (i.e., within 60 days prior to initiating treatment with pomalidomide) serum free light chains (SFLC) as detected by serum free light chain assay (SFLCA) is provided

e. Pomalidomide will NOT be used in combination with another immunomodulatory agent (i.e., thalidomide or lenalidomide)

f. The dosage does not exceed 4 mg daily and will be obtained using the fewest number of capsules possible

Approval duration: 6 months

Continuation of pomalidomide (Pomalyst) meets the definition of medical necessity when ALL of the following criteria are met:

1. Authorization or reauthorization for pomalidomide has been previously approved by Florida Blue or another health plan in the past 2 years for the treatment of multiple myeloma or systemic light chain amyloidosis, OR the member previously met ALL indication-specific initiation criteria.

2. Documentation of a favorable response to treatment is provided (see indication-specific criteria below):

a. Multiple myeloma:

i. If less than18 months of treatment – a serum M-protein value decrease of 25% or more* compared to baseline, or M-protein is undetectable, AND no increase in the size or number of lytic bone lesions after at least two cycles of treatment with pomalidomide – laboratory documentation of the follow-up serum-M protein must be submitted†,#

ii. 18 or more months of treatment - provider attestation that the member had not had disease progression during pomalidomide treatment

*If the M-protein was undetectable by SPEP at baseline and a baseline SFLCA is available, a decrease of 25% or more in the difference between the light chain produced by the myeloma cells (lambda or kappa) and the other light chain must be achieved

†If the M-protein was undetectable by SPEP at baseline and a baseline SFLCA is available, laboratory documentation of a follow-up SFLCA must be submitted

#An exception is permitted if a baseline M-protein AND SFLCA are unavailable. In these cases the physician may provide an attestation of a beneficial clinical response which must include no increase in the size or number of lytic bone lesions.

b. Systemic light chain amyloidosis:

i. If less than18 months of treatment - there has been a reduction (improvement) in the member’s SFLC level as compared to baseline¥ after at least two cycles of treatment with pomalidomide - laboratory documentation of the SFLC level must be submitted

ii. If 18 or more months of treatment - provider attestation that the member had not had disease progression during pomalidomide treatment

¥An exception is permitted if a baseline SFLC value is unavailable. Follow-up laboratory documentation of the SFLC level still must be submitted. The physician must provide an attestation of a beneficial clinical response.

3. Pomalidomide is NOT being used in combination with another immunomodulatory agent (i.e., thalidomide or lenalidomide)

4. The dosage does not exceed the following:

a. Multiple myeloma - 4 mg daily for 21 days of a 28-day cycle and will be obtained using the fewest number of capsules possible.

b. Systemic light chain amyloidosis - 4 mg daily and will be obtained using the fewest number of capsules possible.

Approval duration: 12 months

DOSAGE/ADMINISTRATION:

THIS INFORMATION IS PROVIDED FOR INFORMATIONAL PURPOSES ONLY AND SHOULD NOT BE USED AS A SOURCE FOR MAKING PRESCRIBING OR OTHER MEDICAL DETERMINATIONS. PROVIDERS SHOULD REFER TO THE MANUFACTURER’S FULL PRESCRIBING INFORMATION FOR DOSAGE GUIDELINES AND OTHER INFORMATION RELATED TO THIS MEDICATION BEFORE MAKING ANY CLINICAL DECISIONS REGARDING ITS USAGE.

FDA-approved: pomalidomide is indicated in combination with dexamethasone for treatment of multiple myeloma in persons who have received at least two prior therapies including lenalidomide (Revlimid®) and a proteasome inhibitor and have demonstrated disease progression on or within 60 days of completion of last therapy. The recommended dose is 4 mg daily on days 1 to 21 of repeated 28-day cycles until disease progression. View the package insert for dexamethasone dosage recommendations. Pomalidomide should be taken without food (at least 2 hours before or 2 hours after a meal) and capsules should be administered intact. Women of childbearing age must have negative pregnancy testing and use contraception methods prior to pomalidomide initiation.

Dose Adjustments in MM Treatment

Hematologic Toxicity: Table 1 denotes dose modification instructions for hematologic toxicities.

Table 1

Pomalidomide Dose Modification Instructions for Hematologic Toxicities

Toxicity

Dose Modification

Re-initiation Instructions

Neutropenia

1st episode: ANC less than 500/mcL OR fever† plus ANC less than 1,000/mcL

Interrupt treatment, follow CBC weekly

Once ANC returns to 500/mcL or more, resume at 3 mg daily

Subsequent episodes of ANC less than 500/mcL

Interrupt treatment, follow CBC

Once ANC returns to 500/mcL or more, resume at 1 mg less than previous dose

Thrombocytopenia

1st episode: PLT less than 25,000/mcL

Interrupt treatment, follow CBC weekly

Once PLT return to 50,000/mcL or more, resume at 3 mg daily

Subsequent episodes of PLT less than 25,000/mcL

Interrupt treatment, follow CBC

Once PLT return to 50,000/mcL or more, resume at 1 mg less than previous dose

ANC, absolute neutrophil count; CBC, complete blood count; PLT, platelets

Fever: temperature more than or equal to 38.5°C (101.3°F)

To initiate a new cycle of pomalidomide, the ANC must be at least 500/mcL and the PLT must be at least 50,000/mcL. If toxicities occur after dose reductions to 1 mg, then discontinue.

• Dermatologic: Permanently discontinue pomalidomide for angioedema, skin exfoliation, bullae, or any other severe dermatologic reaction.

• Other Grade 3 or 4 toxicities: Hold treatment and restart treatment at 1 mg less than the previous dose when toxicity has resolved to less than or equal to Grade 2 at the physician’s discretion.

• Strong CYP1A2 Inhibitors in the Presence of Strong CYP3A4 and P-gp Inhibitors: Avoid co-administration of strong inhibitors of CYP1A2. If necessary to co-administer strong inhibitors of CYP1A2 in the presence of strong inhibitors of CYP3A4 and P-gp, reduce pomalidomide dose by 50%.

• Renal and Hepatic Impairment: Avoid use in patients with a serum creatinine greater than 3 mg/dL; these patients were excluded from clinical studies. Avoid use in patients with serum bilirubin greater than 2 mg/dL and AST/ALT greater than 3 x ULN; these patients were excluded from clinical studies.

Drug Availability: pomalidomide is supplied as 1, 2, 3, and 4 mg capsules. Because of the embryo-fetal risk, pomalidomide is available only through a restricted program under a Risk Evaluation and Mitigation Strategy (REMS) program called “Pomalyst REMS”. Further information about the REMS program is available at celgeneriskmanagement.com or by telephone at 1-888-423-5436.

PRECAUTIONS:

Boxed Warning

Embryo-fetal toxicity: Pomalidomide is a thalidomide analogue. Thalidomide is a known human teratogen that causes severe life-threatening birth defects. In women of child-bearing potential, pregnancy should be ruled out (i.e., 2 negative pregnancy tests) prior to pomalidomide initiation. During therapy and for 4 weeks after discontinuation, two forms of reliable methods of contraception or abstaining from sex should be used to prevent pregnancy.

• Venous thromboembolism: Deep vein thrombosis (DVT), myocardial infarction, stroke, and pulmonary embolism (PE) may occur in persons with multiple myeloma treated with pomalidomide. Prophylactic anti-thrombotic measures were used in clinical trials. Thromboprophylaxis is recommended and the choice of regimen should be based on assessment of the individual’s underlying risk factors.

Contraindications: Pregnancy

Warnings

Hematologic toxicity: Neutropenia and other hematologic toxicities may occur; monitor CBC weekly for the first 8 weeks and then monthly thereafter.

Hepatotoxicity: Hepatic failure including fatalities; monitor liver function tests monthly.

Hypersensitivity reactions: Angioedema and severe dermatologic reactions have been reported. Persons with a history of serious hypersensitivity associated with either thalidomide or lenalidomide were excluded from clinical trials and may be at higher risk of hypersensitivity.

Tumor Lysis Syndrome (TLS): Monitor patients at risk of TLS (i.e., those with high tumor burden) and take appropriate precautions.

BILLING/CODING INFORMATION:

HCPCS Coding:

C9399

Unclassified drugs or biologicals (Hospital Outpatient Use ONLY)

J8999

Prescription drug, oral, chemotherapeutic, Not otherwise specified

ICD-10 Diagnoses Codes That Support Medical Necessity:

C90.00

Multiple myeloma not having achieved remission

C90.02

Multiple myeloma in relapse

C90.10

Plasma cell leukemia not having achieved remission

C90.12

Plasma cell leukemia in relapse

C90.20

Extramedullary plasmacytoma not having achieved remission

C90.22

Extramedullary plasmacytoma in relapse

C90.30

Solitary plasmacytoma not having achieved remission

C90.32

Solitary plasmacytoma in relapse

E85.9

Amyloidosis, unspecified

REIMBURSEMENT INFORMATION:

Refer to section entitled POSITION STATEMENT.

PROGRAM EXCEPTIONS:

Federal Employee Program (FEP): Follow FEP guidelines.

State Account Organization (SAO): Follow SAO guidelines.

Medicare Advantage products: No National Coverage Determination (NCD) and/or Local Coverage Determination (LCD) were found at the time of the last guideline review date.

Medicare Part D: BCBSF has delegated to Prime Therapeutics authority to make coverage determinations for the Medicare Part D services referenced in this guideline.

DEFINITIONS:

Heavy chain – the larger component of an immunoglobulin. There are five types: IgG, IgA, IgM, IgD, and IgE.

Immunoglobulins (a.k.a., antibodies) proteins made by normal plasma cells that have an important role in fighting infection as part of the humoral immune response. Antibodies are composed of two heavy chains and two light chains that form a larger complex. Each plasma cell produces only one type of heavy chain and one type of light chain.

Light chain – the smaller component of an immunoglobulin. There are two types: kappa and lambda.

Minimal response (MR) (according to the Revised Uniform Response Criteria by the International Myeloma Working Group)ALL of the following:

• ≥25% but ≤49% reduction of serum M-protein

• Reduction in 24-hour urine M-protein by 50% to 89%

• In addition, if present at baseline, 25% to 49% reduction in size of soft tissue plasmacytomas is also required

No increase in size or number of lytic bone lesions (development of compression fractures dose not exclude response).

Myeloma Protein (M-Protein) – a nonfunctional immunoglobulin protein or protein fragment produced by malignant plasma cells (or myeloma cells). Since myeloma cells are monoclonal, the M-proteins for a given patient are structurally identical. Both portions of an immunoglobulin (the heavy chain and light chain) can be found in the serum, while only light chains can be found in the urine.

Plasma cell - a fully differentiated B lymphocyte (a type of white blood cell) that is specialized for immunoglobulin production and is found primarily in bone marrow.

Primary refractory MM - patients who never achieve at least a MR to initial induction therapy and progress while on therapy

Progressive MM - at least a 25% increase from nadir in the serum M-protein (absolute increase must be ≥0.5 g/dL) or urine M-protein (absolute increase must be ≥200mg/24 hours), or in the difference between involved and uninvolved serum-free light-chain (FLC) levels (with an abnormal FLC ratio and FLC difference >100 mg/L).

Relapsed and refractory MM - patients who never achieve at least a MR or who progress within 60 days of their last therapy

Serum free light chain assay (SFLCA) – a test that detects the amount of unbound or free light chains (i.e., not attached to a heavy chain) in the serum. Normal values - kappa: 3.3 to 19.4 mg/L, lambda: 5.71 to 26.3 mg/L, kappa/lambda ratio: 0.26–1.65 (0.37–3.1 if renal impairment).

Serum Protein Electrophoresis (SPEP) – a test that detects and quantifies the amount of M-protein in the serum. An serum M-protein of greater than 30 g/L is consistent with a diagnosis of MM.

Smoldering (Asymptomatic) myeloma: defined as M-protein in serum of 30 g/dL or more AND/OR bone marrow clonal plasma cells of 10% or more and no related organ or tissue impairment (no end organ damage, including bone lesions) or symptoms.

RELATED GUIDELINES:

Allogeneic Bone Marrow and Stem Cell Transplantation, 02-38240-01
Bortezomib (Velcade) IV, 09-J0000-92

Carfilzomib (Kyprolis), 09-J1000-81

Daratumumab (Darzalex) IV, 09-J2000-49

Doxorubicin HCl Liposome (Doxil) IV, 09-J0000-91

Elotuzumab (Empliciti®) IV, 09-J2000

Interferons for Oncology Use, 09-J1000-37

Ixazomib (Ninlaro), 09-J2000-51

Lenalidomide (Revlimid), 09-J0000-80

Melphalan, Captisol-Enabled (Evomela®) IV, 09-J2000-61

Panobinostat (Farydak), 09-J2000-37

Thalidomide (Thalomid) Capsules, 09-J1000-56

OTHER:

None

REFERENCES:

  1. Baz RC, Martin TG 3rd, Lin HY, et al. Randomized multicenter phase 2 study of pomalidomide, cyclophosphamide, and dexamethasone in relapsed refractory myeloma. Blood. 2016 May 26;127(21):2561-8.
  2. Clinical Pharmacology [database online]. Tampa, FL: Gold Standard, Inc.; 2017. Available at: www.clinicalpharmacilogy-ip.com. Accessed 5/25/17.
  3. Darzalex (daratumumab) injection [package insert]. Horsham, PA: Janssen Biotech, Inc. June 2017.
  4. Dispenzieri A, Buadi F, Laumann K, et al. Activity of pomalidomide in patients with immunoglobulin light-chain amyloidosis. Blood 2012; 119(23):5397-5404.
  5. Gertz M and Merlini G. Definition of organ involvement and response to treatment in AL amyloidosis: an update consensus opinion [abstract]. Amyloid 2010 17(Suppl 1):48-49. (Abstract CP-B).
  6. Micromedex® Healthcare Series [Internet Database]. Greenwood Village, Colo: Thomson Healthcare. Updated periodically. Accessed 5/25/17.
  7. National Comprehensive Cancer Network. Cancer Guidelines. Cancer Guidelines and Drugs and Biologics Compendium. Accessed 09/25/17.
  8. National Comprehensive Cancer Network. Clinical Practice Guidelines in Oncology. Version 1.2018. Multiple Myeloma. Available at http://www.nccn.org/professionals/physician_gls/PDF/myeloma.pdf. Accessed 09/25/17.
  9. National Comprehensive Cancer Network. Clinical Practice Guidelines in Oncology. Version 1.2018. Systemic Light Chain Amyloidosis. Available at http://www.nccn.org/professionals/physician_gls/pdf/amyloidosis.pdf. Accessed 09/25/17.
  10. Pomalyst (pomalidomide) [package insert]. Celgene Corporation. Summit (NJ): June 2016.
  11. Shah JJ, Stadtmauer EA, Abonour R, et al. Carfilzomib, pomalidomide, and dexamethasone for relapsed or refractory myeloma. Blood. 2015 Nov 12;126 (20):2284-90.

COMMITTEE APPROVAL:

This Medical Coverage Guideline (MCG) was approved by the BCBSF Pharmacy Policy Committee on 10/11/17.

GUIDELINE UPDATE INFORMATION:

06/15/13

New Medical Coverage Guideline.

07/15/14

Review and revision to guideline; consisting of updating position statement, references, and coding.

07/15/15

Review and revision to guideline; consisting of updating description, position statement, dosage/administration, precautions, billing/coding, definitions, and references.

11/01/15

Revision: ICD-9 Codes deleted.

07/15/16

Review and revision to guideline consisting of updating description section, position statement, billing/coding information, definitions, related guidelines, and references.

12/15/16

Revision to guideline consisting of updating the description section, position statement, and references based on updated NCCN guidelines for multiple myeloma.

02/16/17

Revision: Update to Position Statement.

07/15/17

Review and revision to guideline consisting of updating the description section, position statement, and references.

11/15/17

Revision to guideline consisting of updating the description section, position statement, and references.

Date Printed: December 17, 2017: 04:27 PM