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Date Printed: June 23, 2017: 06:32 PM

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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-J0000-80

Original Effective Date: 11/15/08

Reviewed: 10/12/16

Revised: 06/15/17

Subject: Lenalidomide (Revlimid®)

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.

           
Dosage/ Administration Position Statement Billing/Coding Reimbursement Program Exceptions Definitions
           
Related Guidelines Other References Updates  
           

DESCRIPTION:

Lenalidomide (Revlimid®) is a chemical derivative of thalidomide. While the mechanism of action of lenalidomide is not completely understood, it is known that the agent possesses immunomodulatory properties that result in the inhibition of pro-inflammatory cytokines and cell proliferation of some cell lines. Additionally, lenalidomide inhibits growth factor-induced endothelial cell migration.

Lenalidomide was first approved by the U.S. Food and Drug Administration (FDA) in December 2005 for the treatment of patients with transfusion-dependent anemia due to Low- or Intermediate-1-risk myelodysplastic syndromes (MDS) associated with a deletion 5q cytogenetic abnormality. Lenalidomide was then FDA-approved for the treatment of multiple myeloma (MM) in patients who have received at least one prior therapy in June 2006 and then mantle cell lymphoma (MCL) in patients whose disease has relapsed or progressed after two prior therapies in June 2013. The MM indication was expanded to include first-line treatment in February 2015. Lenalidomide was previously granted orphan designation for its FDA-approved indications (MM – 2001, anemia due to MDS – 2004, and MCL – 2009), and also has designations for various off-label indications (chronic lymphocytic leukemia – 2007, diffuse large B-cell lymphoma – 2011, follicular lymphoma – 2013, and extranodal marginal zone lymphoma of mucosa-associated lymphoid tissue (MALT) – 2015).

National Comprehensive Cancer Network (NCCN) Guidelines for B-cell Lymphoma (1.2017), Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma (Version 2.2017), Multiple Myeloma (Version 3.2016), Myelodysplastic Syndromes (Version 1.2017), and Systemic Light Chain Amyloidosis (Version 1.2016) include category 1 and/or 2A recommendations for use of lenalidomide in some capacity in each disease state and/or disease subtypes.

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 lenalidomide (Revlimid®) meets the definition of medical necessity for members diagnosed with ANY of the following conditions when ALL associated criteria are met, AND lenalidomide will NOT be used in combination with another immunomodulatory drug [i.e., pomalidomide (Pomalyst®) or thalidomide (Thalomid®)]:

1. Multiple Myeloma (MM)

a. Member has active (symptomatic) multiple myeloma

b. Laboratory documentation of the member’s baseline (i.e., within 30 days prior to initiating treatment with lenalidomide) serum monoclonal protein (M-protein) as detected by serum protein electrophoresis (SPEP) is provided.

c. EITHER of the following (“i” or “ii”):

i. Maintenance therapy following stem cell transplant or maintenance therapy after primary therapy for non-transplant candidates: member’s dosage does not exceed 15 mg daily, and will be obtained using the fewest number of capsules possible

ii. All other therapies: member’s dosage does not exceed 25 mg daily on days 1 to 21 of a 28-day cycle, and will be obtained using the fewest number of capsules possible.

2. Systemic Light Chain Amyloidosis (SLCA)

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

b. Laboratory documentation of the member’s baseline (i.e., within 30 days prior to initiating treatment with lenalidomide) serum free light chains (SFLC) as detected by serum free light chain assay (SFLCA) is provided

c. Member is receiving concomitant dexamethasone unless contraindicated or member is steroid-intolerant

d. Member’s dosage does not exceed 25 mg daily on days 1 to 21 of a 28-day cycle, and will be obtained using the fewest number of capsules possible

3. Myelodysplastic Syndromes (MDS)

a. Member has symptomatic anemia requiring red blood cell (RBC) transfusion

b. EITHER of the following (score must be provided):

• IPSS criteria -The member’s MDS is classified as low- or intermediate-1 (INT-1) risk disease defined as an International Prognostic Scoring System (IPSS) score of 1 or less

• IPSS-R criteria – The member’s MDS is classified as very low-, low-, or intermediate-risk disease defined as an revised International Prognostic Scoring System (IPSS-R) score of 4.5 or less

c. Member has EITHER of the following (“i” or “ii”):

i. A confirmed deletion 5q chromosome [del(5q)] abnormality and BOTH of the following (laboratory documentation must be submitted):

o Neutrophil count ≥500 cells/mcL

o Platelet count ≥25,000 cells/mcL

ii. No del(5q) abnormality (or status is unknown) and EITHER of the following (“1” or “2”):

1. BOTH of the following:

o Serum erythropoietin level >500 mU/mL (laboratory documentation must be submitted)

o Member has a low probability of response to immunosuppressive therapy (i.e., antithymocyte globulin with or without cyclosporine) as initial treatment

2. ALL of the following:

o Serum erythropoietin level ≤500 mU/mL (laboratory documentation must be submitted)

o No response after 3 months (or response followed by loss of response) with, or contraindication to erythropoiesis stimulating agent (ESA) treatment [e.g., epoetin (Procrit)] (the specific contraindication must be provided)

o Lenalidomide will be used in combination with an ESA (unless use of an ESA is contraindicated)

d. Member’s dosage does not exceed 10 mg daily

4. Non-Hodgkin Lymphoma (NHL)

a. Treatment is used as second-line or later therapy for relapsed, refractory, or progressive NHL disease (see exception for mantle cell lymphoma)

b. Member is diagnosed with ANY of the following types of NHL, and all associated criteria are met:

• Adult T-Cell leukemia/lymphoma (ATLL) AND lenalidomide is being used for non-responders to first-line therapy for acute disease or lymphoma (NOT to be used for chronic/smoldering ATLL)

• AIDS-related B-cell lymphoma (ANY of the following subtypes) AND the member is a non-candidate for high-dose cytotoxic therapy

o Diffuse large B-cell lymphoma [non-germinal center B-cell (GCB) subtypes only]

o Lymphoma associated with Castleman’s disease

o Primary effusion lymphoma

• Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma (CLL/SLL) – see separate indication #5

• Non-GCB diffuse large B-cell lymphoma (DLBCL) (includes all subtypes except primary cutaneous B-cell lymphomas and primary DLBCL of the CNS) AND the member is a non-candidate for high-dose cytotoxic therapy

• Follicular lymphoma

• Gastric mucosa‐associated lymphoid tissue (MALT) lymphoma

• Mantle cell lymphoma (MCL)

o EITHER of the following:

1. Treatment is used as less aggressive induction therapy for previously untreated disease in combination with rituximab

2. Treatment is used as second-line or later therapy for relapsed, refractory, or progressive disease

• Multicentric Castleman’s disease (CD)

• Mycosis Fungoides (MF)/Sézary Syndrome (SS) (ANY of the following subtypes):

o Stage IB to IIA disease with histologic evidence of folliculotropic or large cell transformation

o Stage IIB with generalized extent tumor, transformed, and/or folliculotropic disease with or without skin-directed therapy

o Stage IV non-Sezary or visceral disease

• Non-gastric MALT lymphoma

• Peripheral T-cell lymphoma (ANY of the following subtypes):

o Angioimmunoblastic T-cell lymphoma (AITL)

o Peripheral T-cell lymphoma (PTCL), not otherwise specified (NOS)

o Enteropathy-associated T-cell lymphoma (EATL)

• Primary cutaneous B-cell lymphoma (ANY of the following subtypes):

o Primary cutaneous marginal zone lymphoma (PCMZL) with extracutaneous disease relapse or progression

o Primary cutaneous follicle center lymphoma (PCFCL) with extracutaneous disease relapse or progression

o Non-GCB primary cutaneous diffuse large B-cell lymphoma, leg type AND the member is a non-candidate for high-dose cytotoxic therapy

• Primary cutaneous CD30+ T-Cell lymphoproliferative disorder (EITHER of the following subtypes):

o Primary cutaneous anaplastic large cell lymphoma (ALCL) with multifocal lesions

o Cutaneous ALCL with regional nodes (excludes systemic ALCL)

• Splenic marginal zone lymphoma

c. Member’s dosage does not exceed 25 mg daily on days 1 to 21 of a 28-day cycle, and will be obtained using the fewest number of capsules possible

5. Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma (CLL/SLL)

a. ANY of the following (“i”, “ii”, or “iii”):

i. Treatment is used as second-line or later therapy for relapsed or refractory disease

ii. Treatment is used as post first-line maintenance therapy for a member who obtained a partial response or better after at least 4 cycles of first-line CLL/SLL induction therapy AND the member is documented as high-risk for early progression [high-risk is defined as either: (1) a minimal residual disease (MRD) level of ≥10-2, or (2) both a MDR level of ≥10-4 to <10-2 AND either an unmutated immunoglobulin heavy-chain variable-region (IGVH) gene or del(17p) mutation] confirmatory laboratory documentation must be submitted

iii. Treatment is used as post second-line maintenance therapy for a member who obtained a partial response or better after treatment for relapsed or refractory disease

b. EITHER of the following depending on the indication for use:

i. For post first- or second-line maintenance therapy lenalidomide will used as monotherapy

ii. Non-maintenance therapy - lenalidomide will be used as either monotherapy or in combination with rituximab

c. Member’s dosage does not exceed the following, and will be obtained using the fewest number of capsules possible

i. For post first- or second-line maintenance therapy – 10 mg daily

ii. Non-maintenance therapy – 25 mg daily

6. Classical Hodgkin Lymphoma (CHL)

a. EITHER of the following:

i. Indication for use is third-line or later therapy for relapsed or refractory disease

ii. Use is for palliative therapy in an older adult (age >60 year) when other treatments are considered too toxic given the patients age and comorbidities

b. Lenalidomide will be used as monotherapy for treatment of the member’s disease

c. Member’s dosage does not exceed 25 mg daily on days 1 to 21 of a 28-day cycle, and will be obtained using the fewest number of capsules possible

Duration of approval: 6 months

Continuation of lenalidomide (Revlimid®) meets the definition of medical necessity when ALL of the following are met:

1. Authorization/reauthorization for lenalidomide has been previously approved by Florida Blue or another health plan in the past 2 years for the treatment of multiple myeloma, systemic light chain amyloidosis, MDS, NHL, CLL/SLL, or classical Hodgkin lymphoma, OR the member previously met ALL indication-specific initiation criteria.

2. ANY of the following based on the indication for use:

a. Multiple myeloma:

i. If less than18 months of treatment – a serum M-protein value decrease of 25% or more* compared to baseline, or is undetectable, AND no increase in the size or number of lytic bone lesions after at least two cycles of treatment with lenalidomide – lab 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 lenalidomide treatment

*An exception is permitted if a baseline serum M-protein value is unavailable. Follow-up lab documentation of the serum-M protein still must be submitted, and the non-lab requirements still must be met (i.e., no increase in the size or number of lytic bone lesion). If the follow-up serum M-protein is still detectable, the physician must provide an attestation of a beneficial clinical response.

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 lenalidomide - 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 lenalidomide 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.

c. Anemia due to MDS: the member is RBC transfusion independent or there has been a reduction in the frequency of transfusion as compared to baseline (i.e., before treatment with lenalidomide) – documentation of transfusion reduction must be submitted

d. Palliative treatment of CHL: member has had a beneficial response to treatment

e. All other indications: the member’s disease has NOT progressed while receiving treatment with lenalidomide

3. Lenalidomide is NOT used in combination with another immunomodulatory drug [i.e., apremilast (Otezla®), pomalidomide (Pomalyst®), or thalidomide (Thalomid®)]

4. The members dosage does not exceed the following:

• Myelodysplastic Syndromes (MDS) – 10 mg daily obtained using the fewest number of capsules possible

• CLL/SLL (maintenance or non-maintenance therapy) - 25 mg daily obtained using the fewest number of capsules possible

• Maintenance therapy following stem cell transplant or maintenance therapy after primary therapy for non-transplant candidates – 15 mg daily obtained using the fewest number of capsules possible

• Other multiple myelemia therapies - 25 mg daily on days 1 to 21 of a 28-day cycle obtained using the fewest number of capsules possible

• All other indications – 25 mg daily on days 1 to 21 of a 28-day cycle obtained using the fewest number of capsules possible

Duration of approval: 1 year

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

Lenalidomide is indicated for the treatment of patients with: (1) multiple myeloma (MM), in combination with dexamethasone; (2) MM, as maintenance following autologous hematopoietic stem cell transplant, (3) transfusion-dependent anemia due to low- or intermediate-1-risk myelodysplastic syndromes associated with a deletion 5q abnormality with or without additional cytogenetic abnormalities; and (4) mantle cell lymphoma whose disease has relapsed or progressed after two prior therapies, one of which included bortezomib.

• Multiple Myeloma (MM): 25 mg once daily orally on Days 1-21 of repeated 28-day cycles until disease progression or unacceptable toxicity. For patients who are ASCT-eligible, hematopoietic stem cell mobilization should occur within 4 cycles of a lenalidomide-containing therapy. For patients > 75 years old, the starting dose of dexamethasone may be reduced. See the product package insert for the recommended dexamethasone dosage.

MM Maintenance Therapy: After adequate hematologic recovery (ANC ≥1,000/mcL and/or platelet counts ≥75,000/mcL), 10 mg once daily continuously on Days 1-28 of repeated 28-day cycles. After 3 cycles of maintenance therapy, the dose can be increased to 15 mg once daily if tolerated.

• Myelodysplastic Syndromes (MDS): 10 mg once daily

• Mantle Cell Lymphoma (MCL): 25 mg once daily orally on Days 1-21 of repeated 28-day cycles until disease progression or unacceptable toxicity.

The capsules should be swallowed whole with water and should not be opened, broken, or chewed.

Limitations of Use (per the product package insert): lenalidomide is not indicated and is not recommended for the treatment of patients with chronic lymphocytic leukemia (CLL) outside of controlled clinical trials.

Dose Adjustments

Renal impairment:

• CrCl >60 mL/min (MDS and MCL) or >50 mL/min (MM): No adjustment needed

• CrCl 30-60 mL/min (MDS and MCL) or 30-50 mL/min (MM): 5 mg once daily (MDS) or 10 mg once daily (MM, MCL)

• CrCl <30 mL/min (not requiring dialysis): 2.5 mg once daily (MDS) or 15 mg every 48 hours (MM, MCL)

• CrCl <30 mL/min (requiring dialysis): 2.5 mg once daily (MDS) or 5 mg once daily, after dialysis on dialysis days (MM, MCL)

Hematologic toxicities: See the product package insert for specific dosage adjustments for thrombocytopenia and/or neutropenia.

Drug Availability

Capsules: 2.5 mg, 5 mg, 10 mg, 15 mg, 20 mg, and 25 mg

PRECAUTIONS:

Boxed Warning

• Embryo-fetal toxicity: If lenalidomide is used during pregnancy, it may cause birth defects or embryo-fetal death. Obtain 2 negative pregnancy tests before starting treatment. Females of reproductive potential must use 2 forms of contraception or continuously abstain from heterosexual sex during and for 4 weeks after treatment. To avoid embryo-fetal exposure, lenalidomide is only available through a restricted distribution program, the REVLIMID REMS® program (formerly known as the “RevAssist®” program).

• Hematologic toxicity (neutropenia, thrombocytopenia): Eighty percent of patients with del 5q myelodysplastic syndromes had to have a dose delay/reduction during the major study. Patients on therapy for del 5q myelodysplastic syndromes should have their complete blood counts monitored weekly for the first 8 weeks of therapy and at least monthly thereafter. Patients may require dose interruption and/or reduction. Patients may require use of blood product support and/or growth factors.

• Venous thromboembolism: a significantly increased risk of deep vein thrombosis (DVT) and pulmonary embolism (PE), as well as risk of myocardial infarction and stroke, was seen in patients with MM who were treated with lenalidomide and dexamethasone. Thromboprophylaxis is recommended and the choice of regimen should be based on an assessment of the patient’s underlying risks. Patients taking concomitant therapies such as erythropoietin stimulating agents or estrogen containing therapies may have an increased risk of thrombosis.

Contraindications

• Pregnancy

• Hypersensitivity to lenalidomide

Precautions/Warnings

• Digoxin: Periodic monitoring of digoxin plasma levels is recommended due to increase exposure during concomitant lenalidomide therapy.

• Increased mortality: serious and fatal cardiac adverse reactions occurred in patients with CLL treated with lenalidomide.

• Tumor lysis syndrome: monitor patients at risk of TLS (i.e., those with high tumor burden) and take appropriate precautions

• Tumor flare reaction: serious tumor flare reactions have occurred during investigational use for chronic lymphocytic leukemia and lymphoma

• Hepatotoxicity: hepatic failure including fatalities; monitor liver function. Stop treatment and evaluate if hepatotoxicity is suspected.

• Second Primary Malignancies (SPM): higher incidences of SPM were observed in controlled trials of patients with multiple myeloma receiving lenalidomide.

• Impaired Stem Cell mobilization: a decrease in the number of CD34+ cells collected after treatment (> 4 cycles) with lenalidomide has been reported. Consider early referral to transplant center.

BILLING/CODING INFORMATION:

The following codes may be used to describe:

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:

B20

Human immunodeficiency virus [HIV] disease (must be billed in combination with C83.30-C83.39, C83.80-C83.89, or C85.80-C85.89)

C81.00 – C81.99

Hodgkin lymphoma

C82.00 – C82.09

Follicular lymphoma grade I

C82.10 – C82.19

Follicular lymphoma grade II

C82.20 – C82.29

Follicular lymphoma grade III, unspecified

C82.30 – C82.39

Follicular lymphoma grade IIIa

C82.40 – C82.49

Follicular lymphoma grade IIIb

C82.60 – C82.69

Cutaneous follicle center lymphoma

C82.90 – C82.99

Follicular lymphoma, unspecified

C83.00 – C83.09

Small cell B-cell lymphoma

C83.10 – C83.19

Mantle cell lymphoma

C83.30 – C83.39

Diffuse large B-cell lymphoma

C83.80 – C83.89

Other non-follicular lymphoma

C84.00 – C84.09

Mycosis fungoides

C84.40 – C84.49

Peripheral T-cell lymphoma, not classified

C84.93

Mature T/NK-cell lymphomas, unspecified, intra-abdominal lymph nodes

C85.80 – C85.89

Other specified types of non-Hodgkin lymphoma

C86.2

Enteropathy-type (intestinal) T-cell lymphoma

C86.5

Angioimmunoblastic T-cell lymphoma

C86.6

Primary cutaneous CD30-positive T-cell proliferations

C88.4

Extranodal marginal zone B-cell lymphoma of mucosa-associated lymphoid tissue [MALT-lymphoma]

C88.8

Other malignant immunoproliferative diseases

C90.00

Multiple myeloma not having achieved remission

C90.01

Multiple myeloma in 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

C90.21

Extramedullary plasmacytoma in remission

C90.22

Extramedullary plasmacytoma in relapse

C90.30

Solitary plasmacytoma not having achieved remission

C90.31

Solitary plasmacytoma in remission

C90.32

Solitary plasmacytoma in relapse

C91.10

Chronic lymphocytic leukemia of B-cell type, not having achieved remission

C92.11

Chronic lymphocytic leukemia of B-cell type, in remission

C91.12

Chronic lymphocytic leukemia of B-cell type, in relapse

C91.50

Adult T-cell lymphoma/leukemia (HTLV-1-associated), not having achieved remission

C91.52

Adult T-cell lymphoma/leukemia (HTLV-1-associated), in relapse

C92.10

Chronic myeloid leukemia, BCR/ABL-positive, not having achieved remission

D46.0

Refractory anemia without ring sideroblasts, so stated

D46.1

Refractory anemia with ring sideroblasts

D46.20 – D46.21

Refractory anemia with excess of blasts

D46.4

Refractory anemia, unspecified

D46.9

Myelodysplastic syndrome, unspecified

D46.A

Refractory cytopenia with multilineage dysplasia

D46.B

Refractory cytopenia with multilineage dysplasia and ringed sideroblasts

D46.C

Myelodysplastic syndrome with isolated del(5q) chromosomal abnormality

D46.Z

Other myelodysplastic syndromes

D47.Z2

Castleman disease

D47.Z9

Other specified neoplasms of uncertain behavior of lymphoid, hematopoietic and related tissue

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

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

DEFINITIONS:

Common Terminology Criteria for Adverse Events (CTCAE) - standardized definitions for adverse events published by the National Cancer Institute to describe the severity of organ toxicity for patients receiving cancer therapy. Toxicity is graded as mild (Grade 1), moderate (Grade 2), severe (Grade 3), or life-threatening (Grade 4), with specific parameters according to the organ system involved.

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).

Multiple Myeloma: a malignant neoplasm of plasma cells in which the plasma cells proliferate and invade the bone marrow, causing destruction of the bone and resulting in pathologic fracture and bone pain. It is the most common type of monoglonal gammopathy, characterized by presence of a monoclonal immunoglobulin (immunoglobulin recognized as a single protein), Bence Jones proteins in the urine, anemia, and lowered resistance to infection. Also called plasma cell myeloma.

Myelodysplastic Syndrome (MDS): any of a group of related bone marrow disorders of varying duration preceding the development of overt acute myelogenous leukemia; they are characterized by abnormal hematopoietic stem cells, aneuia, neutropenia, and thrombocytopenia. Splenomegaly, hepatomegaly and lymphadenopathy may not occur until the onset of leukemia, which may be explosive. Also called preleukemia.

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.

Non-Hodgkin’s Lymphoma: a large group of lymphatic cancers that comprise approximately 90% of all diagnosed lymphomas. All lymphomas are defined as cancerous growth of lymphocytes, better known as white blood cells, which are the body's primary defense against infection and disease. In lymphoma, these lymphocytes mutate and reproduce uncontrollably, crowding out healthy cells and forming tumors.

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.

Plasmacytoma : a discrete tumor consisting of neoplastic, monoclonal (originating from a single cell) plasma cells in either bone or soft tissue (extramedullary).

Refractory (cancer): cancer that does not respond to treatment. The cancer may be resistant at the beginning of treatment or it may become resistant during treatment.

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

Azacitidine (Vidaza®) Injection, 09-J0000-84

Bortezomib (Velcade®) IV, 09-J0000-92

Carboplatin (Paraplatin®) IV, 09-J0000-93

Carfilzomib (Kyprolis) IV, 09-J1000-81

Cytogenetic Studies (Chromosomal Studies), 05-82000-18

Daratumumab (Darzalex) IV, 09-J2000-49

Docetaxel (Taxotere®) IV, 09-J0000-95

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

Elotuzumab (Empliciti) Injection, 09-J2000

Erythropoiesis Stimulating Agents, 09-J0000-31

Granulocyte Colony Stimulating Factors, 09-J0000-62

Interferons for Oncology Use, 09-J1000-37

Ixazomib (Ninlaro), 09-J2000-51

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

Oprelvekin; Interleukin 11 (Neumega®), 09-J0000-63

Panobinostat (Farydak®), 09-J2000-37

Pomalidomide (Pomalyst®) Capsule, 09-J1000-95

Thalidomide (Thalomid®) Capsules, 09-J1000-56

Zoledronic Acid IV (Reclast®; Zometa®) 09-J0000-72

OTHER:

International Prognostic Scoring System (IPSS)

 

Score Value

Prognostic variable

0

0.5

1

1.5

2

Marrow blasts (%)

<5

5 to 10

--

>10 to 20

>20 to 30

Karyotype

Good

Intermediate

Poor

--

--

Cytopenia*

0 or 1

2 or 3

     

• Low: score of 0

• INT-1: score of 0.5 or 1

• INT-2: score of 1.5 or 2

• High: score of 2.5 or greater

*Neutrophil count <1,800/mcL, platelets <100,000/mcL, Hb <10 g/dL

Revised International Prognostic Scoring System (IPSS)

 

Score Value

Prognostic variable

0

0.5

1

1.5

2

3

4

Cytogenetic

Very good

--

Good

--

Intermediate

Poor

Very poor

Marrow blasts (%)

<2

--

>2 to <5

--

5 to 10

>10

--

Hemoglobin (g/dL)

≥10

--

8 to <10

<8

--

--

--

Platelets

(per mcL)

≥100,000

50,000 to <100,000

<50,000

       

ANC

(per mcL)

≥800

<800

         

• Very low: score of ≤1.5

• Low: score of >1.5 to 3

• Intermediate: score of >3 to 4.5

• High: score of >4.5 to 6

• Very High: score of >6

Website to calculator tool: http://www.ipss-r.com/

REFERENCES:

  1. B-cell Lymphomas treatment guidelines [Internet]. Version 1.2017. Fort Washington (PA): National Comprehensive Cancer Network; 2016 [cited 2016 December 21]. Available from: https://www.nccn.org/professionals/physician_gls/pdf/b-cell.pdf
  2. Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma [Internet]. Version 2.2017. Fort Washington (PA): National Comprehensive Cancer Network; 2017 [cited 2017 May 1]. Available from: https://www.nccn.org/professionals/physician_gls/pdf/cll.pdf
  3. Clinical Pharmacology [Internet]. Tampa (FL): Gold Standard, Inc.; 2016 [cited 2016 Sept 23]. Available from: http://www.clinicalpharmacology.com/.
  4. Dispenzieri A, Lacy MQ, Zeldenrust SR, et al. The activity of lenalidomide with or without dexamethasone in patients with primary systemic amyloidosis. Blood. 2007 Jan 15;109(2):465-70. Epub 2006 Sep 28.
  5. DRUGDEX® System [Internet]. Greenwood Village (CO): Thomson Micromedex; Updated periodically [cited 2016 Sept 23]. Available from: http://www.thomsonhc.com/.
  6. Fehniger TA, Larson S, Trinkaus K, et al. A phase 2 multicenter study of lenalidomide in relapsed or refractory classical Hodgkin lymphoma. Blood. 2011 Nov 10;118(19):5119-25. Epub 2011 Sep 21.
  7. Fink AM, Bahlo J, Sandra R, et al. Lenalidomide maintenance after frontline therapy substantially prolongs progression free survival in high risk CLL: Interim results of a phase 3 study (CLL M1 study of the German CLL Study Group). Paper presented at: American Society of Hematology 58th Annual Meeting; December 3-6, 2016; San Diego, CA. Abstract 229.
  8. Foa R, Schuh A, Zaritskey A, et al. Results of the Phase 3 Study of Lenalidomide Versus Placebo As Maintenance Therapy Following Second-Line Treatment for Patients with Chronic Lymphocytic Leukemia (the CONTINUUM Trial). Paper presented at: American Society of Hematology 58th Annual Meeting; December 3-6, 2016; San Diego, CA. Abstract 230.
  9. Gertz MA, Comenzo R, Falk RH, et al. Definition of organ involvement and treatment response in immunoglobulin light chain amyloidosis (AL): a consensus opinion from the 10th International Symposium on Amyloid and Amyloidosis, Tours, France, 18-22 April 2004. Am J Hematol. 2005 Aug;79(4):319-28.
  10. Greenberg P, Cox C, LeBeau MM, et al. International scoring system for evaluating prognosis in myelodysplastic syndromes. Blood. 1997 Mar 15;89(6):2079-88.
  11. Greenberg PL, Tuechler H, Schanz J, et al. Revised international prognostic scoring system for myelodysplastic syndromes. Blood. 2012 Sep 20;120(12):2454-65. Epub 2012 Jun 27.
  12. Hodgkin lymphoma treatment guidelines [Internet]. Version 3.2016. Fort Washington (PA): National Comprehensive Cancer Network; 2015 [cited 2016 Sept 26]. Available from: http://www.nccn.org/professionals/physician_gls/pdf/hodgkins.pdf
  13. Kumar SK, Hayman SR, Buadi FK, et al. Lenalidomide, cyclophosphamide, and dexamethasone (CRd) for light-chain amyloidosis: long-term results from a phase 2 trial. Blood. 2012 May 24;119(21):4860-7.
  14. Multiple Myeloma treatment guidelines [Internet]. Version 3.2016. Fort Washington (PA): National Comprehensive Cancer Network; 2016 [cited 2016 Sept 27]. Available from: http://www.nccn.org/professionals/physician_gls/pdf/myeloma.pdf
  15. Myelodysplastic Syndromes treatment guidelines [Internet]. Version 1.2016. Fort Washington (PA): National Comprehensive Cancer Network; 2015 [cited 2015 Sept 27]. Available from: http://www.nccn.org/professionals/physician_gls/pdf/mds.pdf
  16. NCCN Drugs & Biologics Compendium [Internet]. Fort Washington (PA): National Comprehensive Cancer Network; 2017 [cited 2017 May 1]. Available from: http://www.nccn.org/professionals/drug_compendium/content/contents.asp.
  17. Orphan Drug Designations and Approval [Internet]. Silver Spring (MD): US Food and Drug Administration; 2016 [cited 2016 Sept 23]. Available from: http://www.accessdata.fda.gov/scripts/opdlisting/oopd/index.cfm.
  18. Revlimid (lenalidomide) capsule [package insert]. Celgene Corporation: Summit, NJ. February 2017. .
  19. Ruan J, Martin P, Shah B, et al. Lenalidomide plus Rituximab as Initial Treatment for Mantle-Cell Lymphoma. N Engl J Med. 2015 Nov 5;373(19):1835-44.
  20. Systemic Light Chain Amyloidosis treatment guidelines [Internet]. Version 1.2016. Fort Washington (PA): National Comprehensive Cancer Network; 2016 [cited 2016 Sept 26]. Available from: http://www.nccn.org/professionals/physician_gls/pdf/amyloidosis.pdf.

COMMITTEE APPROVAL:

This Medical Coverage Guideline (MCG) was approved by the BCBSF Pharmacy Policy Committee on 10/12/16.

GUIDELINE UPDATE INFORMATION:

11/15/08

New Medical Coverage Guideline.

11/15/09

Review and Revision; consisting of updating references.

02/15/11

Review and Revision; consisting of updating position statement, boxed warnings, coding and references.

11/15/11

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

11/15/12

Review and Revision; consisting of updating position statement, coding and references.

03/15/13

Revision to guideline; consisting of adding quantity limit to position statement.

11/15/13

Review and revision to guideline; consisting of revision and reformatting position statement, dosage/administration, precautions, decision tree, and references.

11/15/14

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

11/01/15

Revision: ICD-9 Codes deleted.

11/15/15

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

10/01/16

Revision: ICD-10 code updates.

11/15/16

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

11/18/16

Revision: updates to Position Statement.

02/15/17

Revision to guideline consisting of updating the description, position statement, and references based on an update to the NCCN guidelines for B-cell lymphomas and CLL/SLL.

02/16/17

Revision: Update to Position Statement.

06/15/17

Revision to guideline consisting of updating the description, position statement, billing/coding, and references based on an update to the NCCN guideline for CLL/SLL regarding lenalidomide maintenance treatment.

Date Printed: June 23, 2017: 06:32 PM