Notification



Notification Issue Date:



Medical Policy Bulletin


Title:Radioimmunotherapy with Ibritumomab Tiuxetan (ZevalinŽ) (Independence Administrators)

Policy #:08.00.08j

This policy is applicable to the Company’s commercial products only. Policies that are applicable to the Company’s Medicare Advantage products are accessible via a separate Medicare Advantage policy database.


The Company makes decisions on coverage based on Policy Bulletins, benefit plan documents, and the member’s medical history and condition. Benefits may vary based on contract, and individual member benefits must be verified. The Company determines medical necessity only if the benefit exists and no contract exclusions are applicable.

When services can be administered in various settings, the Company reserves the right to reimburse only those services that are furnished in the most appropriate and cost-effective setting that is appropriate to the member’s medical needs and condition. This decision is based on the member’s current medical condition and any required monitoring or additional services that may coincide with the delivery of this service.

This Medical Policy Bulletin document describes the status of medical technology at the time the document was developed. Since that time, new technology may have emerged or new medical literature may have been published. This Medical Policy Bulletin will be reviewed regularly and be updated as scientific and medical literature becomes available. For more information on how Medical Policy Bulletins are developed, go to the About This Site section of this Medical Policy Web site.



Policy

Coverage is subject to the terms, conditions, and limitations of the member's contract.

BLACK BOX WARNINGS

Refer to the specific manufacturer's prescribing information for any applicable Black Box Warnings.

MEDICALLY NECESSARY

A single course of radioimmunotherapy with ibritumomab tiuxetan (ZevalinŽ) is considered medically necessary and, therefore, covered for the following non-Hodgkin's lymphoma (NHL)--related indications:

FOLLICULAR LYMPHOMA
  • In the treatment of individuals with relapsed or refractory, CD20-positive, low-grade or follicular, B-cell NHL, including individuals with rituximab-refractory follicular NHL
  • In the treatment of individuals with previously untreated CD20-positive, B-cell follicular NHL who achieve a partial or complete response to first-line chemotherapy
  • In the initial treatment of low grade, CD20-positive, B-cell follicular NHL in individuals unable to tolerate standard chemotherapy (e.g., elderly or infirm individuals)
  • In the treatment of histologic transformation of follicular lymphoma (grade 1-2) to diffuse large B-cell lymphoma (DLBCL) in individuals who have received:
    • Minimal or no chemotherapy prior to histologic transformation to DLBCL and have partial response, no response, or progressive disease after chemoimmunotherapy, or
    • Multiple prior therapies including two or more lines of chemoimmunotherapy for indolent or transformed disease

MARGINAL ZONE LYMPHOMA
  • As a subsequent therapy for histologic transformation of marginal zone lymphoma to diffuse large B-cell lymphoma (DLBCL) in individuals who have received:
    • Minimal or no chemotherapy prior to histologic transformation to DLBCL and have partial response, no response, or progressive disease after chemoimmunotherapy, or
    • Multiple prior therapies including two or more lines of chemoimmunotherapy for indolent or transformed disease

PRIMARY CUTANEOUS DIFFUSE LARGE B-CELL LYMPHOMA
  • As a second-line or subsequent therapy for relapsed or refractory primary cutaneous diffuse large B-cell lymphoma (DLBCL), leg type


EXPERIMENTAL/INVESTIGATIONAL

The use of ibritumomab tiuxetan (ZevalinŽ) beyond a single course of treatment is considered experimental/investigational and, therefore, not covered because the safety and/or effectiveness of this regimen cannot be established by review of the available published literature.

All other uses of ibritumomab tiuxetan (ZevalinŽ) are considered experimental/investigational and, therefore, not covered unless the indication is supported as an accepted off-label use, as defined in the medical policy on off-label coverage for prescription drugs and biologics.

REQUIRED DOCUMENTATION

The individual's medical record must reflect the medical necessity for the care provided. These medical records may include, but are not limited to: records from the professional provider's office, hospital, nursing home, home health agencies, therapies, and test reports.

The Company may conduct reviews and audits of services to our members, regardless of the participation status of the provider. All documentation is to be available to the Company upon request. Failure to produce the requested information may result in a denial for the service.
Guidelines

IBRITUMOMAB TIUXETAN (ZEVALINŽ) REGIMEN

On November 18, 2011, the FDA approved the removal of the Indium-111 imaging dose and dosimetry (bioscan) requirements as part of the ibritumomab tiuxetan (ZevalinŽ) treatment regimen. The simplified treatment protocol now consists of two doses of rituximab (RituxanŽ) followed by a single dose of ibritumomab tiuxetan (ZevalinŽ), with the following administration schedule:*

Day 1Administer Rituximab (RituxanŽ) 250 mg/m2 given intravenously (IV)
Day 7, 8, or 9Administer Rituximab (RituxanŽ) 250 mg/m2 IV infusion
  • If platelets ≥ 150,000/mm3: Within 4 hours after rituximab (RituxanŽ) infusion, administer 0.4 mCi/kg (14.8 MBq per kg) ibritumomab tiuxetan (ZevalinŽ) intravenous
  • If platelets ≥ 100,000 but ≤ 149,000/mm3 in relapsed or refractory individuals: Within 4 hours after rituximab (RituxanŽ) infusion, administer 0.3 mCi/kg (11.1 MBq per kg) ibritumomab tiuxetan (ZevalinŽ) intravenous
*Because the ibritumomab tiuxetan (ZevalinŽ) therapeutic regimen includes the use of rituximab (RituxanŽ), please see the full prescribing Information for rituximab (RituxanŽ) at http://www.rituxan.com/index.html.

Per the product labeling, the safety and effectiveness of ibritumomab tiuxetan (ZevalinŽ) in pediatric individuals have not been established.

PRECAUTIONS

The ibritumomab tiuxetan (ZevalinŽ) therapeutic regimen is intended as a single-course treatment. The safety and toxicity profile from multiple courses of the ibritumomab tiuxetan (ZevalinŽ) therapeutic regimen or of other forms of therapeutic irradiation preceding, following, or in combination with the ibritumomab tiuxetan (ZevalinŽ) therapeutic regimen have not been established.

Y-90 Ibritumomab tiuxetan (ZevalinŽ) is a radiopharmaceutical and should be used only by physicians and other professionals trained in and qualified for the safe use and handling of radionuclides.

BENEFIT APPLICATION

Subject to the terms and conditions of the applicable benefit contract, ibritumomab tiuxetan (ZevalinŽ) is covered under the medical benefits of the Company’s products when the medical necessity criteria listed in this medical policy are met.

US FOOD AND DRUG ADMINISTRATION (FDA) STATUS

The FDA approval of ibritumomab tiuxetan (ZevalinŽ) was issued on February 19, 2002. A supplemental approval for ibritumomab tiuxetan (ZevalinŽ) has since been issued by the FDA.

On November 18, 2011, the FDA approved the removal of the Indium-111 imaging dose and dosimetry (bioscan) requirements as part of the ibritumomab tiuxetan (ZevalinŽ) treatment regimen.

Description

Radioimmunotherapy is a treatment for cancer that combines monoclonal antibodies (genetically engineered antibodies that bind with target antigens on specific cells) with radioactive isotopes to destroy cancer cells. Ibritumomab tiuxetan (ZevalinŽ) is an IgG1 kappa monoclonal antibody that is directed against the CD20 antigen, which is found on the surface of normal and malignant B lymphocytes. Treatment with ibritumomab tiuxetan (ZevalinŽ) results in quick and sustained depletion of circulating B-cells. The resultant B lymphocyte elimination begins to reverse in 12 weeks, and normal B lymphocyte levels are achieved approximately nine months after treatment. The radioisotopes in ibritumomab tiuxetan (ZevalinŽ) are indium-111 (In-111) for imaging use and yttrium-90 (Y-90) for therapeutic use.

Ibritumomab tiuxetan (ZevalinŽ) was initially approved by the US Food and Drug Administration (FDA) as a biological product for the secondary treatment of relapsed or refractory, low-grade, follicular, or transformed B-cell non-Hodgkin's lymphoma (NHL), including rituximab-refractory follicular NHL. The FDA's approval was based on two clinical studies involving 197 individuals. One study included 54 individuals who had relapsed follicular NHL that was refractory to rituximab treatment. The overall response rate was 74 percent, and the median duration of response was 6.4 months. The second study compared treatment with ibritumomab tiuxetan (ZevalinŽ) to treatment with rituximab alone. Seventy-three of the 143 individuals enrolled in the study were treated with ibritumomab tiuxetan (ZevalinŽ). The overall response rate with ibritumomab tiuxetan (ZevalinŽ) was 80 percent; with rituximab it was 56 percent. The median duration of response was 13.9 months with ibritumomab tiuxetan (ZevalinŽ) and 11.8 months with rituximab.

In September 2009, the FDA granted supplemental approval for ibritumomab tiuxetan (ZevalinŽ) for a new indication: individuals with previously untreated follicular NHL who achieve a partial or complete response to first-line chemotherapy. It was based on a multi-center, randomized, open-label study of 414 individuals who had follicular NHL with a partial or complete response upon completion of first-line chemotherapy. Individuals were randomized to receive ibritumomab tiuxetan (ZevalinŽ) (n=208) or no further therapy (n=206). Individuals received one of the following first-line chemotherapy regimens: single-agent chlorambucil, fludarabine, or a fludarabine-containing regimen; a cyclophosphamide-containing combination chemotherapy (e.g., cyclophosphamide-hydroxydaunorubicin hydrochloride-oncovin-prednisone regimen [CHOP]); or a rituximab-containing combination chemotherapy. The main efficacy outcome measure was progression-free survival (PFS). PFS was significantly prolonged among individuals treated with ibritumomab tiuxetan (ZevalinŽ) (with a PFS median of 28 months) compared to those receiving no further treatment (with a PFS median of 18 months).

The National Comprehensive Cancer Network (NCCN) Drugs and Biologics Compendium recognizes ibritumomab tiuxetan (ZevalinŽ) in the treatment of follicular lymphoma, marginal zone lymphoma, and primary cutaneous diffuse large B-cell lymphoma (leg type).

Radioimmunotherapy with ibritumomab tiuxetan (ZevalinŽ) must be used with rituximab. Ibritumomab tiuxetan (ZevalinŽ) is intended as a single-course treatment; the toxicity of repeat doses of Y-90 ibritumomab tiuxetan (ZevalinŽ) has not been investigated.

On November 18, 2011, the FDA approved the removal of the Indium-111 imaging dose and dosimetry (bioscan) requirements as part of the ibritumomab tiuxetan (ZevalinŽ) treatment regimen. This simplified treatment protocol now consists of two doses of rituximab (RituxanŽ) followed by a single dose of ibritumomab tiuxetan (ZevalinŽ).

There may be additional indications contained in the Policy section of this document due to evaluation of criteria highlighted in the Company's off-label policy, and/or review of professional clinical guidelines.
References


Abou-Nassar KE, Stevenson KE, Antin JH, et al. (90)Y-ibritumomab tiuxetan followed by reduced-intensity conditioning and allo-SCT in patients with advanced follicular lymphoma. Bone Marrow Transplant. 2011;46(12):1503-1509.

American Hospital Formulary Service (AHFS). Drug Information 2012. Ibritumomab tiuxetan.[STAT!Ref Web site]. Available at: http://online.statref.com [via subscription only]. Accessed August 3, 2017.

Auger-Quittet S, Duny Y, Daures JP, et al. Outcomes after (90) Yttrium-ibritumomab tiuxetan-BEAM in diffuse large B-cell lymphoma: a meta-analysis. Cancer Med. 2014;3(4):927-938.

Bethge W, Lange T, Meisner C, et al. Radioimmunotherapy with yttrium-90-ibritumomab tiuxetan as part of a reduced-intensity conditioning regimen for allogeneic hematopoietic cell transplantation in patients with advanced non-Hodgkin lymphoma: results of a phase 2 study. Blood. 2010;116(10):1795-1802.

Bethge WA, von Harsdorf S, Bornhauser M, et al. Dose-escalated radioimmunotherapy as part of reduced intensity conditioning for allogeneic transplantation in patients with advanced high-grade non-Hodgkin lymphoma. Bone Marrow Transplant. 2012;47(11):1397-402.

Bouabdallah K, Furst S, Asselineau J, et al. 90Y-ibritumomab tiuxetan, fludarabine, busulfan and antithymocyte globulin reduced-intensity allogeneic transplant conditioning for patients with advanced and high-risk B-cell lymphomas. Ann Oncol. 2015;26(1):193-198.

Briones J, Novelli S, Garcia-Marco JA, et al. Autologous stem cell transplantation after conditioning with yttrium-90 ibritumomab tiuxetan plus BEAM in refractory non-Hodgkin diffuse large B-cell lymphoma: results of a prospective, multicenter, phase II clinical trial. Haematologica. 2014;99(3):505-510.

Centers for Medicare & Medicaid Services (CMS). Decision memo for radioimmunotherapy for non-Hodgkin's lymphoma (CAG-00163N). [CMS Web site]. 07/25/05. Available at: http://www.cms.gov/medicare-coverage-database/details/nca-decision-memo.aspx?NCAId=38&NcaName=Radioimmunotherapy+for+Non-Hodgkin%2527s+Lymphoma&DocID=CAG-00163N&id=38&bc=gAAAAAgAIAAA&. Accessed November 21, 2018.

Devizzi L, Guidetti A, Seregni E, et al. Long-Term Results of Autologous Hematopoietic Stem-Cell Transplantation After High-Dose 90Y-Ibritumomab Tiuxetan for Patients With Poor-Risk Non-Hodgkin Lymphoma Not Eligible for High-Dose BEAM. J Clin Oncol. 2013;31(23):2974-2976.

Devizzi L, Guidetti A, Tarella C, et al. High-dose yttrium-90-ibritumomab tiuxetan with tandem stem-cell reinfusion: an outpatient preparative regimen for autologous hematopoietic cell transplantation. J Clin Oncol. 2008;26(32):5175-5182.

Emmanouilides C. Radioimmunotherapy for non-Hodgkin lymphoma: historical perspective and current status. J Clin Exp Hematopathol. 2007;47(2):43-60.

Emmanouilides C. Review of Y-ibritumomab tiuxetan as first-line consolidation radio-immunotherapy for B-cell follicular non-Hodgkin's lymphoma. Cancer Manag Res. 2009;1:131-136.

Forstpointner R, Dreyling M. Rituximab maintenance versus radioimmunotherapy consolidation in follicular lymphoma: which, when, and for whom? Curr Hematol Malig Rep. 2011;6(4):207-215.

Gisselbrecht C, Vose J, Nademanee A, et al. Radioimmunotherapy for stem cell transplantation in non-Hodgkin’s lymphoma: in pursuit of a complete response. Oncologist. 2009;14(suppl 2):41-51.

Gopal AK, Guthrie KA, Rajendran J, et al. (9)(0)Y-Ibritumomab tiuxetan, fludarabine, and TBI-based nonmyeloablative allogeneic transplantation conditioning for patients with persistent high-risk B-cell lymphoma. Blood. 2011;118(4):1132-1139.

Gordon LI, Witzig T, Molina A, et al. Yttrium 90-labeled ibritumomab tiuxetan radioimmunotherapy produces high response rates and durable remissions in patients with previously treated B-cell lymphoma. Clin Lymphoma. 2004;5(2):98-101.

Han EJ, Lee SE, Kim SH, et al. Clinical outcomes of post-remission therapy using (90)yttrium ibritumomab tiuxetan (Zevalin(R)) for high-risk patients with diffuse large B-cell lymphoma. Ann Hematol. 2011;90(9):1075-1082.

Hohloch K, Lankeit HK, Zinzani PL, et al. Radioimmunotherapy for first-line and relapse treatment of aggressive B-cell non-Hodgkin lymphoma: an analysis of 215 patients registered in the international RIT-Network. Eur J Nucl Med Mol Imaging. 2014;41(8):1585-92.

Ibatici A, Pica GM, Nati S, et al. Safety and efficacy of (90) yttrium-ibritumomab-tiuxetan for untreated follicular lymphoma patients. An Italian cooperative study. Br J Haematol. 2014;164(5):710-716.

Illidge TM, Mayes S, Pettengell R, et al. Fractionated (9)(0)Y-ibritumomab tiuxetan radioimmunotherapy as an initial therapy of follicular lymphoma: an international phase II study in patients requiring treatment according to GELF/BNLI criteria. J Clin Oncol. 2014;32(3):212-218.

Jacobs SA, Swerdlow SH, Kant J, et al. Phase II trial of short-course CHOP-R followed by 90Y-ibritumomab Tiuxetan and extended rituximab in previously untreated follicular lymphoma. Clin Cancer Res. 2008;14(21):7088-7094.

Jo JC, Yoon DH, Kim S, et al. Yttrium-90 ibritumomab tiuxetan plus busulfan, cyclophosphamide, and etoposide (BuCyE) versus BuCyE alone as a conditioning regimen for non-Hodgkin lymphoma. Korean J Hematol. 2012;47(2):119-125.

Khouri IF, Saliba RM, Erwin WD, et al. Nonmyeloablative allogeneic transplantation with or without 90yttrium ibritumomab tiuxetan is potentially curative for relapsed follicular lymphoma: 12-year results. Blood. 2012;119(26):6373-6378.

Kirshnan A, Palmer J, Tsai N, et al. Matched-cohort analysis of autologous hematopoietic cell transplantation with radioimmunotherapy versus total body irradiation-based conditioning for poor-risk diffuse large cell lymphoma. Biol Blood Marrow Transplant. 2012;18(3):441-450.

Kluin-Nelemans HC, Hoster E, Hermine O, et al. Treatment of Older Patients with Mantle-Cell Lymphoma. NEJM. 2012;367(6):520-531.

Kolstad A, Laurell A, Jerkeman M, et al. Nordic MCL3 study: 90Y-ibritumomab-tiuxetan added to BEAM/C in non-CR patients before transplant in mantle cell lymphoma. Blood. 2014;123(19):2953-2959.

Morschhauser F, Dreyling M, Rohatiner A, et al. Rationale for consolidation to improve progression-free survival in patients with non-Hodgkin’s lymphoma: a review of the evidence. Oncologist. 2009;14(suppl 2):17-29.

Morschhauser F, Illidge T, Huglo D, et al. Efficacy and safety of yttrium-90 ibritumomab tiuxetan in patients with relapsed or refractory diffuse large B-cell lymphoma not appropriate for autologous stem-cell transplantation. Blood. 2007;110(1):54-58.

Morschhauser F, Radford J, Hoof A, et al. Phase III trial of consolidation therapy with yttrium-90-ibritumomab tiuxetan compared with no additional therapy after first remission in advanced follicular lymphoma. J Clin Oncol.2008;(26)32:5156-5164.

Morschhauser F, Radford J, Van Hoof A, et al. 90Yttrium-ibritumomab tiuxetan consolidation of first remission in advanced-stage follicular non-Hodgkin lymphoma: updated results after a median follow-up of 7.3 years from the International, Randomized, Phase III First-LineIndolent trial. J Clin Oncol. 2013;31(16):1977-1983.

National Comprehensive Cancer Network (NCCN). NCCN Clinical Practice Guidelines in Oncology - B-cell Lymphomas. v.5.2018. [NCCN Web site]. 10/2/2018. Available at: https://www.nccn.org/professionals/physician_gls/pdf/b-cell.pdf [via subscription only]. Accessed November 21, 2018.

National Comprehensive Cancer Network (NCCN). NCCN Drugs & Biologics CompendiumŽ. Ibritumomab tiuxetan. [NCCN Web site]. Available at:
http://www.nccn.org/professionals/drug_compendium/MatrixGenerator/Matrix.aspx?AID=126. Accessed November 21, 2018.

Palanca-Wessels M, Press OW. Improving the efficacy of radioimmunotherapy for non-Hodgkin lymphomas. Cancer. 2010;116(4 Suppl):1126-1133.

Persky DO, Miller TP, Unger JM, et al. Ibritumomab consolidation after 3 cycles of CHOP plus radiotherapy in high-risk limited-stage aggressive B-cell lymphoma: SWOG S0313. Blood. 2015;125(2):236-241.

Press OW. Evidence mounts for the efficacy of radioimmunotherapy for B-cell lymphomas. J Clin Oncol. 2008;26(32):5147-5150.

Provencio M, Cruz Mora MA, Gomez-Codina J, et al. Consolidation treatment with Yttrium-90 ibritumomab tiuxetan after new induction regimen in patients with intermediate- and high-risk follicular lymphoma according to the follicular lymphoma international prognostic index: a multicenter, prospective phase II trial of the Spanish Lymphoma Oncology Group. Leuk Lymphoma. 2014;55(1):51-55.

Ria R, Musto P, Reale A, et al. 90Y-ibritumomab tiuxetan as consolidation therapy after autologous stem cell transplantation in aggressive non-Hodgkin lymphoma. J Nucl Med. 2011;52(6):891-895.

Rose AC, Shenoy PJ, Garrett G, et al. A Systematic Literature Review and Meta-Analysis of Radioimmunotherapy Consolidation for Patients With Untreated Follicular Lymphoma. Clin Lymphoma Myeloma Leuk. 2012;12(6):393-399.

Scholz CW, Pinto A, Linkesch W, et al. 90Yttrium-Ibritumomab-Tiuxetan as First-Line Treatment for Follicular Lymphoma: 30 Months of Follow-Up Data From an International Multicenter Phase II Clinical Trial. J Clin Oncol. 2013;31(3):308-313.

Shimoni A, Avivi I, Rowe JM, et al. A randomized study comparing yttrium-90 ibritumomab tiuxetan (Zevalin) and high-dose BEAM chemotherapy versus BEAM alone as the conditioning regimen before autologous stem cell transplantation in patients with aggressive lymphoma. Cancer. 2012;118(19):4706-4714.

Shimoni A, Zwas S, Oksman Y, et al. Ibritumomab tiuxetan (Zevalin) combined with reduced-intensity conditioning and allogeneic stem-cell transplantation (SCT) in patients with chemorefractory non-Hodgkin’s lymphoma. Bone Marrow Transplant. 2008;41(4):355-361.

Smith MR, Li H, Gordon L, et al. Phase II Study of Rituximab Plus Cyclophosphamide, Doxorubicin, Vincristine, and Prednisone Immunochemotherapy Followed by Yttrium-90-Ibritumomab Tiuxetan in Untreated Mantle-Cell Lymphoma: Eastern Cooperative Oncology Group Study E1499. J Clin Oncol. 2012;30(25):3119-3126.

Stevens PL, Oluwole O, Reddy N. Advances and application of radioimmunotherapy in non-Hodgkin lymphoma. Am J Blood Res. 2012;2(2):86-97.

Tomblyn M. Radioimmunotherapy for B-cell non-hodgkin lymphomas. Cancer Control. 2012;19(3):196-203.

US Food and Drug Administration (FDA). ZevalinŽ (ibritumomab tiuxetan) prescribing information. [FDA Web site]. Revised August 2013. Available at: http://zevalin.com/downloads/Zevalin_Package_Insert.pdf. Accessed November 21, 2018.

US Food and Drug Administration (FDA). Center for Drug Evaluation and Research. ZevalinŽ. Approval letter. [FDA Web site]. 02/19/2002. Available at: https://www.accessdata.fda.gov/drugsatfda_docs/appletter/2002/ibriide021902L.htm. Accessed November 21, 2018.

US Food and Drug Administration (FDA). Center for Drug Evaluation and Research. ZevalinŽ (ibritumomab tiuxetan). Supplemental approval letter. [FDA Web site]. 09/03/09. Available at: http://www.accessdata.fda.gov/drugsatfda_docs/appletter/2009/125019s0156ltr.pdf. Accessed November 21, 2018.

Wiseman GA, White CA, Sparks RB, et al. Biodistribution and dosimetry results from a phase III prospectively randomized controlled trial of Zevalin radioimmunotherapy for low-grade, follicular, or transformed B-cell non-Hodgkin's lymphoma. Crit Rev Oncol Hematol. 2001;39(1-2):181-194.

Wiseman GA, White CA, Stabin M, et al. Phase I/II 90Y-Zevalin (yttrium-90 ibritumomab tiuxetan, IDEC-Y2B8) radioimmunotherapy dosimetry results in relapsed or refractory non-Hodgkin's lymphoma. Eur J Nucl Med. 2000;27(7):766-777.

Witzig TE, Flinn IW, Gordon LI, et al. Treatment with ibritumomab tiuxetan radioimmunotherapy in patients with rituximab-refractory follicular non-Hodgkin’s lymphoma. J Clin Oncol. 2002;20(15):3262-3269.

Witzig TE, Gordon LI, Cabanillas F, et al. Randomized controlled trial of Yttrium-90-labeled ibritumomab tiuxetan radioimmunotherapy versus rituximab immunotherapy for patients with relapsed or refractory low-grade, follicular, or transformed B-cell non-Hodgkin’s lymphoma. J Clin Oncol. 2002;20(10):2453-2463.

Witzig TE, Hong F, Micallef IN, et al. A phase II trial of RCHOP followed by radioimmunotherapy for early stage (stages I/II) diffuse large B-cell non-Hodgkin lymphoma: ECOG3402. Br J Haematol. 2015;170(5):679-86.

Zinzani PL, Rossi G, Franceschetti S, et al. Phase II trial of short-course R-CHOP followed by 90Y-ibritumomab tiuxetan in previously untreated high-risk elderly diffuse large B-cell lymphoma patients. Clin Cancer Res. 2010;16(15):3998-4004.

Zinzani PL, Tani M, Fanti S, et al. A phase II trial of CHOP chemotherapy followed by yttrium 90 ibritumomab tiuxetan (Zevalin) for previously untreated elderly diffuse large B-cell lymphoma patients. Ann Oncol. 2008;19(4):769-773.





Coding

Inclusion of a code in this table does not imply reimbursement. Eligibility, benefits, limitations, exclusions, precertification/referral requirements, provider contracts, and Company policies apply.

The codes listed below are updated on a regular basis, in accordance with nationally accepted coding guidelines. Therefore, this policy applies to any and all future applicable coding changes, revisions, or updates.

In order to ensure optimal reimbursement, all health care services, devices, and pharmaceuticals should be reported using the billing codes and modifiers that most accurately represent the services rendered, unless otherwise directed by the Company.

The Coding Table lists any CPT, ICD-9, ICD-10, and HCPCS billing codes related only to the specific policy in which they appear.

CPT Procedure Code Number(s)

79403


Professional and outpatient claims with a date of service on or before September 30, 2015, must be billed using ICD-9 codes. Professional and outpatient claims with a date of service on or after October 1, 2015, must be billed using ICD-10 codes.

Facility/Institutional inpatient claims with a date of discharge on or before September 30, 2015, must be billed with ICD-9 codes. Facility/Institutional inpatient claims with a date of discharge on or after October 1, 2015, must be billed with ICD-10 codes.


ICD - 10 Procedure Code Number(s)

N/A


Professional and outpatient claims with a date of service on or before September 30, 2015, must be billed using ICD-9 codes. Professional and outpatient claims with a date of service on or after October 1, 2015, must be billed using ICD-10 codes.

Facility/Institutional inpatient claims with a date of discharge on or before September 30, 2015, must be billed with ICD-9 codes. Facility/Institutional inpatient claims with a date of discharge on or after October 1, 2015, must be billed with ICD-10 codes.


ICD -10 Diagnosis Code Number(s)

See Attachment A


HCPCS Level II Code Number(s)

A9543 Yttrium Y-90 ibritumomab tiuxetan, therapeutic, per treatment dose, up to 40 millicuries


Revenue Code Number(s)

N/A

Coding and Billing Requirements


Cross References

Attachment A: Radioimmunotherapy with Ibritumomab Tiuxetan (ZevalinŽ) (Independence Administrators)
Description: ICD-10 Codes




Policy History

Revisions from 08.00.08j:
03/04/2019The medical necessity criteria regarding a single course of radioimmunotherapy with ibritumomab tiuxetan (ZevalinŽ) has been revised for the following indications:
  • Follicular Lymphoma
  • Marginal Zone Lymphoma
  • Primary Cutaneous Diffuse Large B-Cell Lymphoma

The following ICD-10 Diagnosis codes were added to Attachment A of this policy: C83.30, C83.31, C83.32, C83.33, C83.34, C83.35, C83.36, C83.37, C83.38, C83.39, C88.4

Revisions from 08.00.08i:
02/14/2018The following indications were removed from the Description and Policy sections of this policy because the National Comprehensive Cancer Network (NCCN) no longer recommends the use of Ibritumomab Tiuxetan (ZevalinŽ) for the treatment of these conditions:
  • Gastric MALT Lymphoma
  • Nongastric MALT Lymphoma
  • Splenic Marginal Zone Lymphoma
  • Nodal Marginal Zone Lymphoma

The following policy statement regarding Follicular Lymphoma was revised as follows:
    FROM:
    • As a first-line therapy alone in elderly or infirm individuals in the setting of comorbidities where tolerability of combination chemotherapy is a concern for stage I or II disease or for individuals with indications for treatment with stage II bulky, stage III, or stage IV disease
    TO:
    • As a first-line therapy alone in elderly or infirm individuals in the setting of comorbidities where tolerability of combination chemotherapy is a concern for stage I (bulky), contiguous stage II (bulky), non-contiguous stage II disease, or for individuals with indications for treatment with stage III or IV disease

The Guidelines addressing Ibritumomab Tiuxetan (ZevalinŽ) Regimen were revised as follows:
    FROM:
      Rituximab (RituxanŽ) 250 mg/m2 IV with ibritumomab tiuxetan ZevalinŽ administered IV within 4 hours of the second rituximab (RituxanŽ) IV administration
    TO:
      Administer Rituximab (RituxanŽ) 250 mg/m2 IV infusion
      • If platelets ≥ 150,000/mm3: Within 4 hours after rituximab (RituxanŽ) infusion, administer 0.4 mCi/kg (14.8 MBq per kg) ibritumomab tiuxetan (ZevalinŽ) intravenous
      • If platelets ≥ 100,000 but ≤ 149,000/mm3 in relapsed or refractory individuals: Within 4 hours after rituximab (RituxanŽ) infusion, administer 0.3 mCi/kg (11.1 MBq per kg) ibritumomab tiuxetan (ZevalinŽ) intravenous

Coding
The following ICD-10 Diagnosis codes have been removed from Attachment A of this policy:
    C83.00, C83.01, C83.02, C83.03, C83.04, C83.05, C83.06, C83.07, C83.08, C83.09, C83.80, C83.81, C83.82, C83.83, C83.84, C83.85, C83.86, C83.87, C83.88, C83.89, C85.10, C85.11, C85.12, C85.13, C85.14, C85.15, C85.16, C85.17, C85.18, C85.19, C85.20, C85.21, C85.22, C85.23, C85.24, C85.25, C85.26, C85.27, C85.28, C85.29, C85.80, C85.81, C85.82, C85.83, C85.84, C85.85, C85.86, C85.87, C85.88, C85.89, C85.90, C85.91, C85.92, C85.93, C85.94, C85.95, C85.96, C85.97, C85.98, C85.99, C88.4, Z85.79


Effective 10/05/2017 this policy has been updated to the new policy template format.


Version Effective Date: 03/04/2019
Version Issued Date: 03/04/2019
Version Reissued Date: N/A

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Independence Blue Cross is an independent licensee of the Blue Cross and Blue Shield Association, serving the health insurance needs of Philadelphia and southeastern Pennsylvania.