chemo drug a-d

Chemotherapy: Drugs A-D Policy1

This section contains policy related to billing for injection services, listed in alphabetical order by generic drug name or drug type. For general billing policy information regarding injections services, refer to the Chemotherapy: An Overview section in this manual. Additional policy information for chemotherapy drug services can be found in the Chemotherapy: Drugs E-O and Chemotherapy: P-Z sections in this manual.

Ado-TrastuzumabAdo-trastuzumab emtansine is a Human Epidermal Growth

EmtansineFactor Receptor 2 (HER2)-targeted antibody-drug conjugate which contains the humanized anti-HER2 IgG1, trastuzumab, covalently linked to the microtubule inhibitory drug DM1 (a maytansine derivative) via the stable thioether linker MCC (4-[N- maleimidomethyl] cyclohexane-1-carboxylate). Emtansine refers to the MCC- DM1 complex. Upon binding to sub-domain IV of the HER2 receptor,
ado- trastuzumab emtansine undergoes receptor-mediated internalization and subsequent lysosomal degradation, resulting in intracellular release of DM1- containing cytotoxic catabolites. Binding of DM1 to tubulin disrupts microtubule networks in the cell, which results in cell cycle arrest and apoptotic cell death.

IndicationsFor the treatment of patients with HER2 positive metastatic breast cancerwho previously received trastuzumab and a taxane, separately or in combination. They should have either:

  • Received prior therapy for metastatic disease, or
  • Developed disease recurrence during or within six months of completing adjuvant therapy

AuthorizationAn approved Treatment Authorization Request (TAR) is required for reimbursement. Documentation must be submitted with the TAR to establish medical necessity.

DosageThe recommended dose of ado-trastuzumab emtansine is 3.6 mg/kg given as an intravenous infusion every three weeks (21-day cycle) until disease progression or unacceptable toxicity. Ado-trastuzumab emtansine should not be administered at doses greater than 3.6 mg/kg nor should it be substituted for or used with trastuzumab.

BillingHCPCS code J9354 (injection, ado-trastuzumab emtansine, 1 mg)

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Chemotherapy: Drugs A-D Policy1

AldesleukinAldesleukin is a lymphokine that stimulates growth of T-lymphocytes. Aldesleukin is used to treat metastatic renal cell carcinoma and metastatic malignant melanoma. It is a “biologic response modifier” that promotes anti-tumor activity mediated through the immune system.

Required CodesAldesleukin is reimbursable when billed in conjunction with ICD-10-CMdiagnosis codes C43.0 – C43.9 (malignant melanoma of skin),
C64.1 – C65.9 (malignant neoplasm of kidney and renal pelvis).

DosageAdult patients diagnosed with metastatic renal cell carcinoma or metastatic malignant melanoma may be treated with a dosage schedule consisting of two five-day treatment cycles separated by a rest period of nine days. Patients receive a dose of 600,000 IU/kg of aldesleukin administered every eight hours through a 15-minute intravenous infusion, for a total of 14 doses. Following the rest period, the schedule is repeated for another 14 doses, to a maximum of28 dosesper course.

BillingHCPCS code J9015 (injection, aldesleukin, per single use vial)

Aldesleukin may be billed in conjunction with CPT-4 code 96413(chemotherapy administration, intravenous infusion technique; up to one hour, single or initial substance/drug).

AprepitantAprepitant injection is a substance P/neurokinin-1 (NK-1) receptor antagonist anti-emetic drug for intravenous (IV) administration.

IndicationsAprepitant is used in combination with dexamethasone and a 5-HT3 receptor antagonist to prevent nausea and vomiting symptoms associated with initial and repeat courses of highly-emetic cancer chemotherapy (HEC) or moderately-emetic cancer chemotherapy (MEC).

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Age18 years and older

DosageSingle Dose Regimen for HEC:

  • 130 mg IV given as a single dose approximately 30 minutes before initiation of a chemotherapy cycle.

Multiple Dose Regimen for MEC:

  • 100 mg IV given approximately 30 minutes before initiation of a chemotherapy cycle on Day 1, followed by an 80 mg aprepitant oral capsule given once daily on Days 2 and 3.

AuthorizationNo Treatment Authorization Request (TAR) is generally required for reimbursement, unless the claim exceeds the recommended maximum dose or frequency.

Required ICD-10-CM CodeZ51.11 (Encounter for anti-neoplastic chemotherapy)

BillingHCPCS code C9463 (injection, aprepitant, 1 mg)

One (1) unit of C9463 = 1 mg of aprepitant emulsion

Arsenic TrioxideThe mechanism of action of arsenic trioxide is not completely understood. Arsenic trioxide causes morphological changes and DNA fragmentation characteristic of apoptosis in NB4 human promyelocytic leukemia cells in vitro.

IndicationsFor the induction of remission and consolidation in patients 4 years of age and older with acute promyelocytic leukemia (APL) who are refractory to, or have relapsed from, retinoid and anthracycline chemotherapy, and whose APL is characterized by the presence of the t(15;17) translocation or PML/RAR alpha gene expression.

DosageRecommended induction treatment schedule:

Intravenously at a dose of 0.15 mg/kg daily until bone marrow remission. Total induction dose should not exceed 60 doses.

Recommended consolidation treatment schedule:

Intravenously at a dose of 0.15 mg/kg daily for 25 doses over a period of five weeks.

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Required CodesArsenic trioxide is reimbursable when billed with one of the following ICD-10-CM diagnosis codes:

  • C92.40
  • C92.41
  • C92.42

BillingHCPCS code J9017 (injection, arsenic trioxide, 1 mg)

AsparaginaseErwiniaAsparaginase Erwinia chrysanthemi contains an asparaginasespecific

Chrysanthemienzyme derived from Erwiniachrysanthemi. Asparaginase Erwinia chrysanthemi catalyzes the deamidation of asparagine to aspartic acid and ammonia, resulting in a reduction in circulating levels of asparagine. The mechanism of action of asparaginase Erwinia chrysanthemi is thought to be based on the inability of leukemic cells to synthesize asparagine due to lack of asparagine synthetase activity, resulting in cytotoxicity specific for leukemic cells that depend on an exogenous source of the amino acid asparagine for their protein metabolism and survival.

IndicationsFor the treatment of patients with acute lymphoblastic leukemia who have developed hypersensitivity to E. coli-derived asparaginase.

DosageTo substitute for a dose of pegaspargase:

The recommended dose is 25,000 International Units/m2 administered intramuscularly three times a week (Monday/Wednesday/Friday) for six doses for each planned dose of pegaspargase.

To substitute for a dose of native E. coli asparaginase:

The recommended dose is 25,000 International Units/m2 administered intramuscularly for each scheduled dose of native E. coli asparaginase within a treatment.

Maximum dose of 50,000 units unless there is documentation thatpatient‘s body surface area (BSA) is greater than 2.6 m2.

Required CodesAsparaginase Erwinia chrysanthemi is reimbursable when billed with one of the following ICD-10-CM diagnosis codes:

C91.00 or C91.02

BillingHCPCS code J9019 (injection asparaginase [erwinaze], 1,000 IU)

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AtezolizumabAtezolizumab is an Fc-engineered, humanized, monoclonal antibody that binds to PD-L1 and blocks interactions with the PD-1 and B7.1 receptors. Atezolizumab is a non-glycosylated IgG1 kappa immunoglobulin that has a calculated molecular mass of 145 kDa. PD-L1 may be expressed on tumor cells and/or tumor-infiltrating immune cells and can contribute to the inhibition of the anti-tumor immune response in the tumor microenvironment. Binding of PD-L1 to the PD-1 and B7.1 receptors found on T cells and antigen presenting cells suppresses cytotoxic T-cell activity, T-cell proliferation and cytokine production.

Atezolizumab is a monoclonal antibody that binds to PD-L1 and blocks its interactions with both PD-1 and B7.1 receptors. This releases the PD-L1/PD-1 mediated inhibition of the immune response, including activation of the anti-tumor immune response without inducing antibody-dependent cellular cytotoxicity.

IndicationsAtezolizumab is indicated for the treatment of patients 18 years of age or olderwith:

  • Locally advanced or metastatic urothelial carcinoma who:

–Have disease progression during or following
platinum-containing chemotherapy

–Have disease progression within 12 months of neoadjuvant or adjuvant treatment with plantinum-containing chemotherapy.

  • Metastatic non-small cell lung cancer who have disease progression during or following platinum-containing chemotherapy. Patients with EGFR or ALK genomic tumor aberrations should have disease progression on FDA-approved therapy for these aberrations prior to receiving Atezolizumab.

AuthorizationAn approved Treatment Authorization Request (TAR) is required for reimbursement. Documentation must indicate that the patient has one of the following diagnoses:

  • Locally advanced or metastatic urothelial carcinoma
  • Metastatic non-small cell lung cancer

DosageAdminister 1,200 mg as an intravenous infusion over 60 minutes every three weeks. Dilute prior to intravenous infusion.

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Required CodesFor the treatment of bladder cancer, use ICD-10-CM diagnosis codes: C67.0, C67.1, C67.2, C67.3, C67.4, C67.5, C67.6, C67.7, C67.8 and C67.9.

For the treatment of lung cancer, use ICD-10-CM diagnosis codes: C34.00, C34.01, C34.02, C34.10, C34.11, C34.12, C34.30, C34.31, C34.32,C34.80, C34.81, C34.82, C34.90, C34.91 and C34.92.

BillingHCPCS code J9022 (injection, atezolizumab, 10 mg)

AvelumabAvelumab is aprogrammed death ligand-1 (PD-L1) blocking antibody, which is a human IgG1 lambda monoclonal antibody. PD-L1 may be expressed on tumor cells and tumor-infiltrating immune cells and can contribute to the inhibition of the anti-tumor immune response in the tumor microenvironment. Binding of PD-L1 to the PD-1 and B7.1 receptors found on T cells and antigen presenting cells suppresses cytotoxic T-cell activity, T-cell proliferation and cytokine production. Avelumab binds PD-L1and blocks the interaction between PD-L1 and its receptors PD-1 and B7.1. This interaction releases the inhibitory effects of PD-L1 on the immune response resulting in the restoration of immune responses, including anti-tumor immune responses. Avelumab has also been shown to induce antibody-dependent
cell-mediated cytotoxicity (ADCC) in vitro. The blocking of PD-L1 activity results in decreased tumor growth.

IndicationsAvelumab is indicated for the treatment of patients 12 years of age and older with metastatic Merkel cell carcinoma.

AuthorizationAn approved TAR is required for reimbursement.

DosageAdminister 10 mg/kg as an intravenous infusion over 60 minutes every two weeks.

Premedicate with acetaminophen and an antihistamine for the first four infusions and subsequently as needed.

Required CodesICD-10-CM diagnosis code C7B.1

BillingHCPCS code J9023 (injection, avelumab, 10 mg)

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Axicabtagene ciloleucelAxicabtagene ciloleucel suspension is a CD19-directed genetically modified autologous T-cell immunotherapy for intravenous (IV) infusion.

IndicationsAxicabtagene ciloleucel is indicated for the treatment of adults with relapsed or refractory large B-cell lymphoma after two or more lines of systemic therapy, including the following:

  • Diffuse large B-cell lymphoma (DLBCL) not otherwise specified,
  • Primary mediastinal large B-cell lymphoma,
  • High grade B-cell lymphoma, or
  • DLBCL arising from Follicular lymphoma.

Axicabtagene ciloleucel is not indicated for the treatment of patients with primary central nervous system lymphoma.

Age18 years and older

DosageA single infusion bag contains a suspension of chimeric antigen receptor (CAR)-positive T cells of 2 x 106 CAR-positive viable T cells per kg body weight, with a maximum of 2 x 108 CAR-positive viable
T cells in approximately 68 mL.

Required CodesAxicabtagene ciloleucel is reimbursable when billed with one of the following ICD-10-CM diagnosis codes:

  • C83.30 – C83.39
  • C85.20 – C85.29

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Authorization:An approved Treatment Authorization Request (TAR) is required for reimbursement.

The TAR must include clinical documentation that demonstrates all of the following:

  • the service is medically necessary to treat an adult with relapsed or refractory large B-cell Lymphoma after two or more lines of systemic therapy;
  • a clinician’s written order and treatment plan for the service has been requested;
  • the provider facility is certified by the YescartaTM REMS (Risk Evaluation and Management Strategy) Program for Axicabtagene ciloleucel administration; and
  • the provider facility is accredited by the Foundation for the Accreditation of Cellular Therapy (FACT) for Immune Effector Cell Therapy (IECT).

Billing:HCPCS code Q2041 (Axicabtagene ciloleucel, up to 200 million autologus anti-CD19 CAR T cells, including leukapheresis and dose preparation procedures, per infusion)

One (1) unit of Q2041 = a single infusion of up to 200 million autologous anti-CD19 CAR-positive viable T cells

AzacitidineAzacitidine is a pyrimidine nucleoside analog of cytidine and is believed to exert its antineoplastic effects by causing hypomethylation of DNA and direct cytotoxicity on abnormal hematopoietic cells in the bone marrow.

IndicationsAzaciditine is indicated for treatment of patients with:

  • Refractory anemia
  • Refractory anemia with ringed sideroblasts (if accompanied by neutropenia or thrombocytopenia or requiring transfusions)
  • Refractory anemia with excess blasts or excess blasts in transformation
  • Chronic myelomonocytic leukemia
  • Acute myeloid leukemia

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DosageThe recommended starting dosage of azacitidine is 75 mg/m2, given subcutaneously or intravenously once a day for seven days. This is usually repeated every four weeks for at least four cycles, and then continued as long as the patient continues to improve. The dosage may be increased to a maximum of 100 mg/m2 if there is no initial response to treatment.

BillingHCPCS code J9025 (injection, azacitidine, 1 mg)

Azacitidine is reimbursable for either intravenous or subcutaneous administration. Azacitidine may be billed either as an I.V. push or I.V. infusion over 40 minutes.

Note:Refer to the Chemotherapy: An Overview section of this manual for both subcutaneous injection and I.V. infusion administration billing codes.

BelinostatBelinostat is a histone deacetylase inhibitor and catalyzes the removal of acetyl groups from the lysine residues of histones and some
non-histone proteins. In vitro, belinostat caused the accumulation of acetylated histones and other proteins, inducing cell cycle arrest and/or apoptosis of some transformed cells with preferential cytotoxicity towards tumor cells compared to normal cells.

IndicationsFor the treatment of patients 18 years of age and older with relapsed or refractory peripheral T-cell lymphoma.

AuthorizationAn approved Treatment Authorization Request (TAR) is required for reimbursement.

DosageThe recommended dose is 1,000 mg/m2 once daily on days 1 through 5 of a 21-day cycle.

BillingHCPCS code J9032 (injection, belinostat, 10mg)

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Bendamustine HClBendeka or bendamustine is a bifunctional mechlorethamine

(Bendeka™)derivative containing a purine-like benzimidazole ring, which is an alkylating drug. Mechlorethamine and its derivatives form electrophilic alkyl groups. These groups form covalent bonds with electron-rich necleophilic moieties, resulting in interstrand DNA crosslinks. The bifunctional covalent linkage can lead to cell death via several pathways. Bendamustine is active against both quiescent and dividing cells.

IndicationBendeka is indicated for the treatment of patients 18 years of age or older with chronic lymphocytic leukemia (CLL). Bendeka is also indicated for the treatment of patients with indolent B-cell non-Hodgkin lymphoma (NHL) that has progressed during or within six months of treatment with rituximab or a rituximab-containing regimen.

AuthorizationAn approved TAR is required for reimbursement. The TAR must state that the treatment is for a patient with CLL or indolent B-cell NHL that has progressed during or within six months of treatment with rituximab or a rituximab-containing regimen.

DosageFor CLL:

  • 100 mg/m2 infused intravenously over 10 minutes on days one and two of a 28-day cycle, for up to six cycles.
  • Dose modifications:

–For hematologic toxicity: for Grade 3 or greater toxicity, reduce dose to 50 mg/m2 on days one and two. If Grade 3 or greater toxicity recurs, reduce the dose to 25 mg/m2 on days one and two.

–For non-hematologic toxicity: for clinically significant Grade 3 or greater toxicity, reduce the dose to 50 mg/m2 on days one and two of each cycle.

For NHL:

  • 120 mg/m2 infused intravenously over 10 minutes on days one and two of a 21-day cycle, for up to eight cycles.
  • Dose modifications

–For hematologic toxicity: for Grade 4 toxicity, reduce the dose to 90 mg/m2 on days one and two of each cycle. If Grade 4 toxicity recurs, reduce the dose to 60 mg/m2 on days one and two of each cycle.

–For non-hemtologic toxicity: for Grade 3 or greater toxicity, reduce the dose to 90 mg/m2 on days one and two of each cycle. If Grade 3 or greater toxicity recurs, reduce the dose to 60 mg/m2 on days one and two of each cycle.

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General Dosing Considerations:

  • Delay treatment for Grade 4 hematologic toxicity or clinically significant Grade 2 or greater non-hemtologic toxicity.

Required CodesICD-10-CM diagnosis codes C82.90 – C82.99, C83.00 – C83.09, C85.80, C85.90 and C91.11

BillingHCPCS code J9034 (injection, bendamustine HCl [Bendeka], 1mg)

Bendamustine HClTreanda or bendamustine HCl is a bifunctional mechlorethamine

(Treanda®)derivative containing a purine-like benzimidazole ring.

Mechlorethamine and its derivatives form electrophilic alkyl groups. These groups form covalent bonds with electron-rich nucleophilic moieties, resulting in interstrand DNA crosslinks. The bifunctional covalent linkage can lead to cell death via several pathways. Bendamustine is active against both quiescent and dividing cells. The exact mechanism of action of bendamustine remains unknown.

IndicationsFor the treatment of patients with:

  • Chronic lymphocytic leukemia or
  • Indolent B-cell non-Hodgkin lymphoma that has progressed during or within six months of treatment with rituximab or a rituximab-containing regimen

Required CodesClaims must be billed in conjunction with one of the following
ICD-10-CM diagnosis codes:

C82.00 – C82.99 / C84.00 – C84.99 / C91.12
C83.00 – C83.19 / C85.10 – C85.99 / C91.40 – C91.42
C83.30 – C83.39 / C86.0 – C86.6 / C96.0
C83.50 – C83.59 / C88.4 / C96.20 – C96.29
C83.80 – C83.99 / C91.10 / C96.A

BillingHCPCS code J9033 (injection, bendamustine HCl [Treanda], 1 mg)

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BevacizumabPolicy for intravitreal bevacizumub (HCPCS code J9035) is located in the Ophthalmology section of the appropriate Part 2 manual.

Bevacizumab is a vascular endothelial growth factor-specific angiogenesis inhibitor and is reimbursable for the treatment of:

  • Metastatic breast cancer, with paclitaxel for treatment of patients who have not received chemotherapy for metastatic HER2-negative breast cancer
  • Unresectable, locally advanced, recurrent or metastatic
    non-squamous, non-small cell lung cancer, with carboplatin and paclitaxel for first line treatment
  • Metastatic colorectal cancer, with intravenous five
    fluorouacil-based chemotherapy for first- or second-line treatment
  • Glioblastoma multiforme, as a single agent for patients with progressive disease following prior therapy
  • Metastatic renal cell carcinoma with interferon alpha
  • Cervical cancer, in combination with paclitaxel and cisplatin or paclitaxel and topotecan in persistent, recurrent, or metastatic disease
  • Platinum-resistant recurrent epithelial ovarian, fallopian tube or primary peritoneal cancer, in combination with paclitaxel, pegylated liposomal doxorubicin or topotecan

DosageThe recommended dosage for bevacizumab varies depending upon the disease being treated.