Monoclonal antibodies, which are currently being used in the diagnosis of certain cancers, are developed from tumor-associated antigens using the hybridoma technology. Typically, the antibodies are harvested from the ascitic fluid of a previously inoculated mouse and either labeled directly to form a radiolabeled monoclonal antibody or digested to give Monoclonal Antibody (McAB) fragments, which subsequently are radiolabeled. The advantages of McAB fragments are rapid liver processing, thus allowing imaging of the liver – an important consideration when liver metastases need to be considered; lower immunogenicity – decreasing significantly the chance of a Human Anti-Mouse Antibody (HAMA) reaction; and the biological half-life is short, allowing for rapid blood clearance and, therefore, improved tumor-to-background ratios.
This LCD will not address the uses of monoclonal antibodies for therapy, but rather only those uses for diagnostic purposes.
A. Radiopharmaceutical agents are radionuclides usually attached to carrier molecules used as adjuncts to nuclear medicine diagnostic or therapeutic procedures. This LCD will address only the diagnostic procedures.
B. The following monoclonal antibodies have been approved for the following indications and procedures:
1. Arcitumomab (CEA-Scan®) (A9568)
Indications
CEA-Scan® is a murine IgG monoclonal FAB (Fragment Antigen-Binding) fragment, Arcitumomab, formulated to be labeled with technectium Te-99m. This antigen is increased in a variety of carcinomas, particularly of the gastrointestinal tract, and is used as a tumor marker for cancers of the colon and rectum. The purpose of its use is to enhance pre-operative determination of resectability.
It has a short (13 plus/minus 4 hours) biological half-life, rapid blood clearance and minimal liver metabolism. Comparison studies with CT scan have shown that this agent provides a 40 percent increase (66 percent vs. 47 percent) in detection of patients with resectable disease, a 143 percent increase (47 percent vs. 19 percent) in detection of patients with non-resectable disease, a 60 percent decrease (23 percent vs. 59 percent) in the False-Negative (FN) rate and a positive-predictive value of 97 percent.
Limitations
- Differential diagnosis of suspected colorectal carcinoma, screening for colorectal carcinoma and assessment of response to treatment are non-covered.
- Medicare will not cover both an OncoScint® and a CEA-Scan® study, since these are duplicative.
2. Capromab Pentetide (ProstaScint®) (A9507) – indium In-III
Indications
ProstaScint® is an intact murine IgG monoclonal antibody scanning technique that uses labeled radioactive indium, which localizes to the sites of Prostate-Specific Membrane Antigen (PSMA). This antigen is associated with prostatic adenocarcinoma cells, with degree of expression being foremost for metastatic lesions, next for primary tumors and much less for non-malignant tissue. When the monoclonal antibody attaches to the antigen, these cells can be detected by gamma camera scanning.
The purpose of the study is to find those patients with a positive test that indicates or confirms metastasis. This makes surgery avoidable and points to other modalities of treatment. An FN test is of no relevance, since an FN test will result in the patient having the surgery.
ProstaScint® shows markedly increased sensitivity over CT (21 vs. 0 detected occurrences in 38 patients), especially in scar or inflamed tissue, or in lymph nodes.
In a study of 51 patients where ProstaScint® was compared with CT, MRI and ultrasound, the true-positive and false-negative tests were 47 percent vs. 26 percent and 4percent vs. 23 percent, respectively, and the sensitivity was 92 percent vs. 53 percent.
Limitations
- Screening for prostate carcinoma, re-administration for assessment of response to treatment and patients not considered high risk for pelvic metastases are considered non-covered.
- ProstaScint® will be covered once in a lifetime only.
3. Nofetumomab Merpentan (Verluma®) (A4641) – unlisted code
Indications
Verluma® is a murine IgG monoclonal antibody fragment that attaches to an approximately 40kD glycoprotein antigen (carcinoma-associated antigen), which is expressed on a variety of cancers and on some normal tissues. It is localized to primary and/or metastatic small-cell lung cancer.
The agent is characterized by a serum half-life of 1.5 hours, with 64 percent of the radiolabel being excreted in the urine; uptake should therefore be expected in the kidneys and the urinary bladder. The advantage of this agent is that it allows accurate staging in a small-cell lung cancer. Since 60 percent of patients with this disease already have extensive disease, with a three-year survival of less than 5 percent, detection of this cohort eliminates the mortality and costs associated with radiation therapy, which would be unnecessary (only chemotherapy would be indicated). If this agent reveals extensive disease, no other imaging modality is needed, since the True-Positive (TP) rate is 94 percent. Studies have shown that this agent detected 29 lesions missed by combined other modalities in 33 patients.
This agent is used exclusively for detection of metastases from biopsy-proven and previously untreated small-cell lung cancer.
Limitations
- Verluma® is not intended for assessment of response or evaluation following chemotherapy or radiation therapy, or to resolve a differential diagnosis between lung carcinoma and metastases.
4. Imciromab Pentetate (MyoScint®) (A4641) – unlisted code
Indications
MyoScint® is the FAB fragment of a murine monoclonal antibody linked to indium via diethylenetriamine penta-acetic acid. The murine antibody binds to the heavy chain of cardiac myosin, an intracellular protein found in heart muscle cells. This myosin is exposed after a loss of integrity of the myocyte cell membrane. This test is highly specific (specificity of 97 percent), since normal myocytes do not take up MyoScint®, and heavy chain myosin is not found free in the circulation. Thus the FAB fragments localize to sites of necrotic myocardium. The extent of cardiac uptake correlates with prognosis (e.g., risk of subsequent cardiac death), and sensitivity ranges from 84 percent acutely to 72 percent at two months post-myocardial infarction. The agent can be injected immediately after the onset of chest pain.
This agent is used to detect the presence and location of myocardial injury in patients with suspected or completed myocardial infarction. It may have diagnostic value when the ECG and cardiac enzyme studies are equivocal.
5. Satumomab Pendetide (OncoScint®) (A4642)
Indications
OncoScint® is a conjugate produced from the murine monoclonal antibody CYT-099 (Mab B72.3). Satumomab is a murine monoclonal antibody of the IgG, kappa subclass that is directed to a high-molecular-weight, tumor-associated glycoprotein (TAG-72). The differential expression of this glycoprotein has been demonstrated in a variety of adenocarcinomas. In in vitro immunohistologic studies, Mab 72.3 has been reported to be reactive with about 83 percent of colorectal adenocarcinomas and reactive in 97 percent of ovarian carcinomas. It is generally not immunoreactive with normal adult tissues, but it is reactive with salivary gland ducts, normal post-ovulatory endometria, some benign ovarian tumors and fetal gastrointestinal tissues.
This agent helps to determine the extent and location of extrahepatic metastases in patients with known colorectal or ovarian cancer.
Limitations
- It is non-covered for the evaluation of patients with suspected primary ovarian or colorectal cancer or screening for colorectal or ovarian cancer.
- Medicare will not cover both an OncoScint® and a CEA-Scan® study, since these are duplicative.
6. Ibritumomab Tiuxetan (Zevalin®, IN-111) (A9542)
Indications
The FDA approved this monoclonal antibody on February 19, 2002. Ibritumomab Tiuxetan, when combined with radioactive chemicals and administered as part of a specific therapeutic regimen, is indicated for the treatment of individuals with relapsed or refractory low-grade, follicular or transformed B-cell non-Hodgkin’s lymphoma, including patients with rituximab refractory, follicular, non-Hodgkin’s lymphoma.
The therapeutic regimen consists of a single course of treatment involving first, as a diagnostic maneuver, the administration of rituximab followed within four hours by the administration of Indium-111 ibritumomab tiuxetan. The biodistribution is assessed by imaging. If the imaging is acceptable, a second dose of rituximab is given on day seven, eight or nine. This is followed within four hours by the administration of Yttrium-90 Zevalin®.
7. Tositumomab and Iodine I-131 (Bexxar®) (A9544)
Indications
The FDA approved this monoclonal antibody on June 27, 2003. The Bexxar® therapeutic regimen (Tositumomab and Iodine I-131) is an anti-neoplastic radioimmunotherapeutic monoclonal antibody-based treatment. It is composed of the monoclonal antibody Tositumomab and the radiolabeled monoclonal antibody Iodine I-131 Tositumomab.
Treatment with Bexxar® is indicated for the treatment of patients with CD20 positive, follicular, non-Hodgkin’s lymphoma, with and without transformation, whose disease is refractory to Rituximab and has relapsed following chemotherapy. Bexxar® is not indicated for the initial treatment of patients with CD20 positive non-Hodgkin’s lymphoma.
Bexxar® consists of four lengthy components administered in two discrete steps: the dosimetric/diagnostic step, followed seven to14 days later by a therapeutic step. This LCD only addresses the dosimetric/diagnostic step.
Notice: This LCD imposes diagnosis limitations that support diagnosis to procedure code automated denials. However, services performed for any given diagnosis must meet all of the indications and limitations stated in this policy, the general requirements for medical necessity as stated in CMS payment policy manuals, any and all existing CMS national coverage determinations, and all Medicare payment rules.
As published in CMS IOM 100-08, Section 13.5.1, to be covered under Medicare, a service shall be reasonable and necessary. When appropriate, contractors shall describe the circumstances under which the proposed LCD for the service is considered reasonable and necessary under Section 1862(a)(1)(A). Contractors shall consider a service to be reasonable and necessary if the contractor determines that the service is:
- Safe and effective.
- Not experimental or investigational (exception: routine costs of qualifying clinical trial services with dates of service on or after September 19, 2000, which meet the requirements of the clinical trials NCD are considered reasonable and necessary).
- Appropriate, including the duration and frequency that is considered appropriate for the service, in terms of whether it is:
- Furnished in accordance with accepted standards of medical practice for the diagnosis or treatment of the patient’s condition or to improve the function of a malformed body member.
- Furnished in a setting appropriate to the patient’s medical needs and condition.
- Ordered and furnished by qualified personnel.
- One that meets, but does not exceed, the patient’s medical need.
- At least as beneficial as an existing and available medically appropriate alternative.
Bill Type Codes
Contractors may specify Bill Types to help providers identify those Bill Types typically used to report this service. Absence of a Bill Type does not guarantee that the policy does not apply to that Bill Type. Complete absence of all Bill Types indicates that coverage is not influenced by Bill Type and the policy should be assumed to apply equally to all claims.
12X, 13X, 18X, 21X, 22X, 23X, 85X
Revenue Codes
Contractors may specify Revenue Codes to help providers identify those Revenue Codes typically used to report this service. In most instances Revenue Codes are purely advisory; unless specified in the policy services reported under other Revenue Codes are equally subject to this coverage determination. Complete absence of all Revenue Codes indicates that coverage is not influenced by Revenue Code and the policy should be assumed to apply equally to all Revenue Codes.
Note: TrailBlazer has identified the Bill Type and Revenue Codes applicable for use with the CPT/HCPCS codes included in this LCD . Providers are reminded that not all CPT/HCPCS codes listed can be billed with all Bill Type and/orRevenue Codes listed. CPT/HCPCS codes are required to be billed with specific Bill Type and Revenue Codes. Providers are encouraged to refer to the CMS Internet-Only Manual Publication 100-04, Claims Processing Manual, for further guidance.
061X, 034X, 035X
CPT/HCPCS Codes
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Note:
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Providers are reminded to refer to the long descriptors of the CPT codes in their CPT book. The American Medical Association (AMA) and CMS require the use of short CPT descriptors in policies published on the Web.
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77300©
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Radiation therapy dose plan
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78800©
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Tumor imaging, limited area
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78801©
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Tumor imaging, mult areas
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78802©
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Tumor imaging, whole body
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78803©
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Tumor imaging (3d)
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78804©
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Tumor imaging, whole body
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A4641
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Radiopharmaceutical, diagnostic, not otherwise classified
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A4642
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Indium in-111 satumomab pendetide, diagnostic, per study dose, up to 6 millicuries
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A9507
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Indium in-111 capromab pendetide, diagnostic, per study dose, up to 10 millicuries
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A9542
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Indium in-111 ibritumomab tiuxetan, diagnostic, per study dose, up to 5 millicuries
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A9544
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Iodine i-131 tositumomab, diagnostic, per study dose
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A9568
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Technetium tc-99m arcitumomab, diagnostic, per study dose, up to 45 millicuries
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G3001
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Administration and supply of tositumomab, 450 mg
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J9310
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Injection, rituximab, 100 mg
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ICD-9-CM Codes That Support Medical Necessity
The CPT/HCPCS codes included in this LCD will be subjected to “procedure to diagnosis” editing. The following lists include only those diagnoses for which the identified CPT/HCPCS procedures are covered. If a covered diagnosis is not on the claim, the edit will automatically deny the service as not medically necessary.
Note: Diagnosis restrictions do not apply to CPT/HCPCS codes 77300, 78800, 78801, 78802, 78803, 78804, G3001 and J9310.
Medicare is establishing the following limited coverage for CPT/HCPCS code A4641 when used to representImciromab Pentetate (MyoScint®):
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410.00–410.02 begin_of_the_skype_highlighting 00–410.02 end_of_the_skype_highlighting
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Acute myocardial infarction of anterolateral wall
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410.10–410.12
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Acute myocardial infarction of other anterior wall
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410.20–410.22
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Acute myocardial infarction of inferolateral wall
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410.30–410.32
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Acute myocardial infarction of inferoposterior wall
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410.40–410.42
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Acute myocardial infarction of other inferior wall
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410.50–410.52
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Acute myocardial infarction of other lateral wall
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410.60–410.62
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True posterior wall infarction
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410.70–410.72
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Subendocardial infarction
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410.80–410.82
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Acute myocardial infarction of other specified sites
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410.90–410.92
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Acute myocardial infarction of unspecified site
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411.1
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Intermediate coronary syndrome
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414.8–414.9
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Other acute and subacute forms of chronic ischemic heart disease
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Medicare is establishing the following limited coverage for CPT/HCPCS code A4641 when used to representNofetumomab Merpentan (Verluma®):
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162.2–162.5
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Malignant neoplasm of trachea, bronchus and lung
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162.8–162.9
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Malignant neoplasm of trachea, bronchus and lung
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231.2
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Carcinoma in situ of bronchus and lung
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Medicare is establishing the following limited coverage for CPT/HCPCS code A4642:
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153.0–153.9
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Malignant neoplasm of colon
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154.0–154.3
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Malignant neoplasm of rectum, rectosigmoid junction and anus
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154.8
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Malignant neoplasm of other sites of rectum, rectosigmoid junction and anus
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183.0
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Malignant neoplasm of ovary
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183.2–183.5
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Malignant neoplasm of ovary and other uterine adnexa
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183.8–183.9
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Malignant neoplasm of ovary and other uterine adnexa
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197.5
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Secondary malignant neoplasm of large intestine and rectum
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198.6
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Secondary malignant neoplasm of ovary
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230.3–230.4
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Carcinoma in situ of digestive organs
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233.31–233.32
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Carcinoma in situ, female genital organs
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233.39
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Carcinoma in situ, other female genital organ
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236.2
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Neoplasm of uncertain behavior of ovary
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Medicare is establishing the following limited coverage for CPT/HCPCS code A9507:
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185
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Malignant neoplasm of prostate
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233.4
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Carcinoma in situ of prostate
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790.93
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Elevated prostate specific antigen [psa]
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Medicare is establishing the following limited coverage for CPT/HCPCS code A9542 and A9544:
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200.30–200.38
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Marginal zone lymphoma
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200.50–200.58
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Primary central nervous system lymphoma
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200.60–200.68
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Anaplastic large cell lymphoma
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200.70–200.78
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Large cell lymphoma
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200.80–200.88
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Lymphosarcoma and reticulosarcoma
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202.00–202.08
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Nodular lymphoma
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202.70–202.78
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Peripheral T cell lymphoma
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202.80–202.88
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Other lymphomas
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Medicare is establishing the following limited coverage for CPT/HCPCS code A9568:
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153.0–153.9
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Malignant neoplasm of colon
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154.0–154.3
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Malignant neoplasm of rectum, rectosigmoid junction and anus
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154.8
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Malignant neoplasm of other sites of rectum rectosigmoid junction and anus
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197.5
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Secondary malignant neoplasm of large intestine and rectum
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230.3–230.4
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Carcinoma in situ of digestive organs
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Note: Providers should continue to submit ICD-9-CM diagnosis codes without decimals on their claim forms and electronic claims.
Diagnoses That Support Medical Necessity
N/A
ICD-9-CM Codes That DO NOT Support Medical Necessity
N/A
Diagnoses That DO NOT Support Medical Necessity
All diagnoses not listed in the “ICD-9-CM Codes That Support Medical Necessity” section of this LCD.
Documentation Requirements
Documentation supporting medical necessity should be legible, maintained in the patient’s medical record and made available to Medicare upon request.
The patient’s medical record should support the reasonable and necessary indications for procedures done.
For A9507 (ProstaScint®):
Documentation should include a diagnosis of prostate cancer or post-prostatectomy with serological evidence of metastases or recurrence (elevated or rising PSA) and negative equivocal findings from other imaging studies.
Documentation should include a diagnosis of prostate cancer or post-prostatectomy with serological evidence of metastases or recurrence (elevated or rising PSA) and negative equivocal findings from other imaging studies.
Appendices
N/A
Utilization Guidelines
- A9507 (ProstaScint®) will be covered once in a lifetime only.
- Medicare will not cover both A4642 (OncoScint®) and A9568 (CEA-Scan® study), since these are duplicative.
Notice: This LCD imposes utilization guideline limitations. Despite Medicare’s allowing up to these maximums, each patient’s condition and response to treatment must medically warrant the number of services reported for payment. Medicare requires the medical necessity for each service reported to be clearly demonstrated in the patient’s medical record. Medicare expects that patients will not routinely require the maximum allowable number of services.
Sources of Information and Basis for Decision
J4 (CO, NM, OK, TX) MAC Integration
TrailBlazer adopted the Noridian Administrative Services, LLC LCD, “Radiopharmaceuticals: Monoclonal Antibodies, Diagnostic,” for the Jurisdiction 4 (J4) MAC transition.
Full disclosure of sources of information is found with original contractor LCDs.
Other Contractor Local Coverage Determinations
“Radiopharmaceuticals: Monoclonal Antibodies, Diagnostic,” Noridian Administrative Services, LLC LCD, (CO) L23872.