Medical Policy


Subject: Radioimmunotherapy and Somatostatin Receptor Targeted Radiotherapy
Document #: THER-RAD.00005 Publish Date:    02/28/2018
Status: Reviewed Last Review Date:    01/25/2018


This document addresses radioimmunotherapy which is a systemic therapy that involves a targeting monoclonal antibody that is combined to a radiation emitting radionuclide to treat certain types of cancer.  The United States (U.S.) Food and Drug Administration (FDA) has approved ibritumomab tiuxetan (ZevalinÒ, Spectrum Pharmaceuticals, Irvine, CA) as a radioimmunotherapy to treat certain types of CD20-positive (CD20+) non-Hodgkin’s Lymphoma (NHL).

Somatostatin receptor therapeutic targeted radiotherapy involves the combination of a somatostatin analogue with a radionuclide to treat certain types of cancer.

Note: Somatostatin analogues that are not radiolabeled have diagnostic and clinical indications that are outside the scope of this document.

Position Statement

Medically Necessary:

Ibritumomab tiuxetan (Zevalin)

A single course of ibritumomab tiuxetan is considered medically necessary for one of the following:

  1. Individuals with CD20+ relapsed or refractory, low-grade or follicular B-cell non-Hodgkin's lymphoma (NHL); or
  2. Individuals with previously untreated CD20+ follicular NHL who achieve a partial or complete response to first-line chemotherapy.

Investigational and Not Medically Necessary:

Ibritumomab tiuxetan (Zevalin)

  1. A single course of ibritumomab tiuxetan, or combinations with other forms of irradiation or chemotherapy, is considered investigational and not medically necessary when the criteria above are not met.
  2. A course of ibritumomab tiuxetan for an individual previously treated with ibritumomab tiuxetan is considered investigational and not medically necessary.
  3. As part of CD20+ lymphoma pre-transplant conditioning regimen ibritumomab tiuxetan is considered investigational and not medically necessary.

Other treatments

  1. The use of other yttrium-labeled humanized antibody therapies is considered investigational and not medically necessary.
  2. Somatostatin analogs (including octreotide, lanreotide and vapreotide) for use as therapeutic receptor targeted radionuclide therapy are considered investigational and not medically necessary for all indications.

Targeted cancer therapies block the growth and spread of cancer by interfering with specific molecules involved in tumor growth and progression (National Cancer Institute [NCI], 2014).  Monoclonal antibodies locate and bind to specified targets on the surface of a cell.  Radioimmunotherapy utilizes monoclonal antibodies to deliver radioactive substances to specific targets on a cancer cell to maximize radiation and cell death while minimizing the effects on normal cells.

Ibritumomab tiuxetan (Zevalin)

In 2002, the FDA granted accelerated approval to ibritumomab tiuxetan for the treatment of individuals with relapsed or refractory low-grade, follicular, or transformed B-cell NHL, including individuals with rituximab-refractory follicular NHL.  In 2009, the FDA expanded the labeled indications to include treatment of individuals with previously untreated follicular NHL who achieve a partial or complete response to first-line chemotherapy.  The single course administration of the ibritumomab tiuxetan therapeutic regimen includes rituximab and Yttrium-90 ibritumomab tiuxetan given in two steps.  The first step involves an infusion of rituximab.  The second step, administered 7 to 9 days after the first, consists of a second infusion of rituximab followed by Y-90 Zevalin.  Ibritumomab tiuxetan has been studied in two clinical settings, as consolidation therapy for lymphoma with a complete or partial response to first line therapy, and secondly as a pre-transplant conditioning regimen.

Ibritumomab tiuxetan as Consolidation Therapy

The FIT trial (first-line induction therapy) was a randomized study comparing treatment with and without ibritumomab tiuxetan consolidation therapy in 414 individuals with advanced stage CD20+ follicular lymphoma who achieved a complete response (CR) or partial response (PR) with first-line (induction) therapy.  Progression-free survival (PFS) at a median of 3.5 years was 36.5 months in the treatment cohort versus. 13.3 months in the control group (p<0.0001) (Morschhauser, 2008).  After a median follow-up of 7.3 years, the PFS benefit continued to favor the Zevalin cohort with an overall PFS of 41% compared to 22% for the control arm (hazard ratio [HR], 0.47; p<0.001) (Morschhauser, 2013).

The National Comprehensive Cancer Network® (NCCN®) Clinical Practice Guidelines ® (2017) provide a category 1 recommendation for the use of radioimmunotherapy as second-line or subsequent therapy for follicular lymphoma and for progressive generalized extracutaneous disease in primary cutaneous B-cell lymphoma.  The latter is based on a retrospective pilot study with 9 individuals enrolled (Maza, 2008). No further studies have been published to validate these findings.

Pre-transplant conditioning regimen

High-dose chemotherapy and hematopoietic stem cell support is an established therapy for individuals with relapsed diffuse large cell lymphoma.  Conditioning regimens prior to the stem cell support typically include total body irradiation (TBI) and Zevalin has been investigated as an alternative.  Clinical studies have focused on both autologous and allogeneic stem cell support, different subtypes of B-cell lymphoma, different chemotherapy regimens and different doses of Zevalin.  Phase II trials have reported promising results (Berger, 2016; Bethge, 2010; Cabrero, 2017; Gopal, 2011; Khouri, 2012; Krishnan, 2012; Nadamanee, 2005), but there have been no randomized trials that have reported that a Zevalin-containing pre-transplant conditioning regimen is associated with improved outcomes.  In the only published randomized study, Shimoni and colleagues (2012) compared the PFS at 2 years in 43 individuals with aggressive NHL randomized to receive a conditioning regimen of BEAM with or without Zevalin followed by autologous stem cell support.  The PFS at 2 years was not significantly different between the 2 groups.  The study was halted early due to slow accrual rates and encouraged larger, long-term studies to determine the optimal conditioning regimens for aggressive NHL.

Given the gaps in the published data, specialty consensus opinion no longer recommends the use of radioimmunotherapy with ibritumomab tiuxetan (Zevalin) as a conditioning regimen for hematopoietic stem cell transplants to treat individuals with NHL.  Specifically, specialty consensus opinion emphasizes the importance of randomized studies to validate the safety and effectiveness of Zevalin in this setting.

There are ongoing phase III trials studying various combinations and sequencing of radioimmunotherapies with or without chemotherapy as a treatment of NHL.  The data from these randomized controlled trials will provide additional guidance for treatment recommendations.

Somatostatin radionuclide analogues

Targeted radiotherapy utilizing somatostatin analogues are currently being investigated for neuroendocrine tumors (e.g., pheochromocytoma, pituitary, carcinoid and medullary thyroid cancer).  Data from phase II trials have been reported in various malignancies, but the data for long-term effectiveness and safety from phase III randomized controlled trials are needed.  The NCCN (2017) clinical guidelines for neuroendocrine tumors do not mention radiolabled somatostatin analogues.  Kulke and colleagues (2011) reported that the Neuroendocrine Tumor (NET) Task Force of the National Cancer Institute GI Steering Committee convened a clinical trials planning meeting to identify key unmet needs, develop appropriate study end points, standardize clinical trial inclusion criteria, and formulate priorities for future NET studies.

The revised American College of Radiology (ACR) and the American Society for Radiation Oncology (ASTRO) guideline for unsealed radiopharmaceutical sources (Henkin, 2011) note radioimmunotherapy for NHL include ibritumomab tiuxetan.  The guidelines did not include any recommendations for radionuclide therapy combined with somatostatin analogues or any other targeting drug or antibody, to treat malignancies.


NHL, the most common hematologic cancer in the United States, is a collection of more than a dozen different cancers of the lymphatic system which generates the body's immune defenses.  NHL can be divided into two prognostic groups: indolent lymphomas and aggressive lymphomas.  Most of the indolent types are nodular (or follicular) in morphology.  Prior to the introduction of monoclonal antibody therapy, the most commonly used therapeutic options for indolent NHL were single-agent alkylating chemotherapy, combination chemotherapy with or without an alkylating agent, lymphoid or total-body irradiation, or a combination of these modalities, including protocols inducing sufficient cytotoxicity to require stem cell transplantation.  Indolent NHL has proven to be highly responsive to treatment with radiation in experimental studies, but the obstacles to external beam delivery in advanced-stage disease may explain its limited efficacy in individuals with relapsed indolent NHL.

Targeted treatments are forms of cancer therapy that take advantage of the biological differences between cancerous and noncancerous cells by "targeting" faulty genes or proteins that contribute to cancer.  Many times these drugs are combined with chemotherapy, radiation, or biological therapy.  Interruption, interference, or inhibition of the target should yield a clinical response in a significant proportion of individuals whose tumors express the target but in few individuals whose tumors do not express the target.  As such, targeted therapy offers the twin hopes of maximizing efficacy while minimizing toxicity.

Adverse Events and Warnings:

Ibritumomab tiuxetan (Zevalin)

The product information label (2013) for ibritumomab tiuxetan includes the following Black Box Warnings and information:

Serious Infusion Reactions

Deaths have occurred within 24 hours of rituximab infusion, an essential component of the Zevalin therapeutic regimen.  These fatalities were associated with hypoxia, pulmonary infiltrates, acute respiratory distress syndrome, myocardial infarction, ventricular fibrillation, or cardiogenic shock.  Most (80%) fatalities occurred with the first rituximab infusion.  Discontinue rituximab and Y-90 Zevalin infusions in patients who develop severe infusion reactions.

Prolonged and Severe Cytopenias

Y-90 Zevalin administration results in severe and prolonged cytopenias in most patients.  Do not administer Y-90 Zevalin to patients with ≥25% lymphoma marrow involvement and/or impaired bone marrow reserve.  Cytopenias with delayed onset and prolonged duration, some complicated by hemorrhage and severe infection, are the most common severe adverse reactions of the Zevalin therapeutic regimen.  When used according to recommended doses, the incidences of severe thrombocytopenia and neutropenia are greater in patients with mild baseline thrombocytopenia (≥100,000 but ≤ 149,000/mm3) compared to those with normal pretreatment platelet counts.  Severe cytopenias persisting more than 12 weeks following administration can occur.  Monitor complete blood counts (CBC) and platelet counts following the Zevalin therapeutic regimen weekly until levels recover or as clinically indicated.

Severe Cutaneous and Mucocutaneous Reactions

Severe cutaneous and mucocutaneous reactions, some fatal, can occur with the Zevalin therapeutic regimen.  Discontinue rituximab and Y-90 Zevalin infusions in patients experiencing severe cutaneous or mucocutaneous reactions.  Erythema multiforme, Stevens-Johnson syndrome, toxic epidermal necrolysis, bullous dermatitis, and exfoliative dermatitis, some fatal, were reported in post-marketing experience.  The time to onset of these reactions was variable, ranging from a few days to 4 months after administration of the Zevalin therapeutic regimen.

Somatostatin radionuclide analogues

Somatostatin is a 14-amino-acid peptide hormone found on many cells of neuroendocrine origin.  It acts as a neurotransmitter in the central nervous system.  Hormonally, when it binds to cells, it inhibits the release of growth hormone, insulin, glucagon and gastrin.  Somatostatin receptors have been demonstrated on the surface of human tumor cells which includes the cells with amine precursor uptake and decarboxylation (APUD) properties such as pituitary tumors, endocrine pancreatic tumors, carcinoids, paragangliomas, small cell lung cancers, medullary thyroid carcinomas and pheochromocytomas.  Other non-APUD cells may also bear somatostatin receptors, such as activated lymphocytes, astrocytomas, and some breast carcinomas. 


Cytotoxic: Chemicals that are directly toxic to cells, preventing their reproduction or growth.

Line of therapy:

Malignant: Cancerous. Malignant cells can invade and destroy nearby tissue and spread to other parts of the body.

Monoclonal antibody: A form of biologic therapy that acts specifically against a particular antigen.

Neuroendocrine: Descriptive of cells that release a hormone into the circulating blood in response to a stimulus.

Non-Hodgkin's Lymphoma (NHL): A group of malignant solid tumors of lymphoid tissues.

Phenotype: The total characteristics displayed by the tumor.

Radioisotope: A radioactive form of an element or isotope.

Radionuclide: An unstable form of a chemical element that releases radiation as it breaks down and becomes more stable. Radionuclides may occur in nature or be made in a laboratory. In medicine, they are used in imaging tests and in treatment; also called radioisotope.

Radiotherapy: Systemic radiotherapy uses a radioactive substance, such as a radiolabeled monoclonal antibody, that travels in the blood to tissues throughout the body.

Refractory disease: Illness or disease that does not respond to treatment.


The following codes for treatments and procedures applicable to this document are included below for informational purposes.  Inclusion or exclusion of a procedure, diagnosis or device code(s) does not constitute or imply member coverage or provider reimbursement policy.  Please refer to the member’s contract benefits in effect at the time of service to determine coverage or non-coverage of these services as it applies to an individual member.

When services may be Medically Necessary when criteria are met:




Radiopharmaceutical therapy, radiolabeled monoclonal antibody by intravenous infusion






Yttrium Y-90 ibritumomab tiuxetan, therapeutic, per treatment dose, up to 40 millicuries [Zevalin therapeutic]



ICD-10 Diagnosis



Follicular lymphoma


Non-follicular lymphoma


Other specified and unspecified types of non-Hodgkin lymphoma


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

When services are Investigational and Not Medically Necessary:
For the procedure codes listed above, when criteria are not met, for all other diagnoses not listed; or when the code describes a procedure indicated in the Position Statement section as investigational and not medically necessary.


Peer Reviewed Publications:

  1. Andrade-Campos MM, Liévano P, Espinosa-Lara N, et al. Long-term complication in follicular lymphoma: assessing the risk of secondary neoplasm in 242 patients treated or not with 90-yttrium-ibritumomab-tiuxetan. Eur J Haematol. 2016; 97(6):576-582.
  2. Ansell SM, Ristow KM, Habermann TM, et al. Subsequent chemotherapy regimens are well tolerated after radioimmunotherapy with yttrium-90 ibritumomab tiuxetan for non-Hodgkin's lymphoma.  J Clin Oncol.  2002; 20(18):3885-3890.
  3. Auger-Quittet S, Duny Y, Daures JP, Quittet P. Outcomes after (90) Yttrium-ibritumomab tiuxetan-BEAM in diffuse large B-cell lymphoma: a meta-analysis. Cancer Med. 2014; 3(4):927-938.
  4. Berger MD, Branger G, Klaeser B, et al. Zevalin and BEAM (Z-BEAM) versus rituximab and BEAM (R-BEAM) conditioning chemotherapy prior to autologous stem cell transplantation in patients with mantle cell lymphoma. Hematol Oncol. 2016; 34(3):133-139.
  5. Bethge WA, 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.
  6. Brabander T, van der Zwan WA, Teunissen JJM, et al. Long-term efficacy, survival, and safety of [177Lu-DOTA0,Tyr3] octreotate in patients with gastroenteropancreatic and bronchial neuroendocrine tumors. Clin Cancer Res. 2017; 23(16):4617-4624.
  7. Cabrero M, Martin A, Briones J, et al. Phase II study of yttrium-90-ibritumomab tiuxetan as part of reduced-intensity conditioning (with melphalan, fludarabine ± thiotepa) for allogeneic transplantation in relapsed or refractory aggressive B cell lymphoma: A GELTAMO Trial. Biol Blood Marrow Transplant. 2017; 23(1):53-59.
  8. Epperla N, Pham AQ, Burnette BL, et al. Risk of histological transformation and therapy-related myelodysplasia/acute myeloid leukaemia in patients receiving radioimmunotherapy for follicular lymphoma. Br J Haematol. 2017; 178(3):427-433.
  9. Fruchart C, Tilly H, Morschhauser F, et al. Upfront consolidation combining Yttrium-90 ibritumomab tiuxetan and high-dose therapy with stem cell transplantation in poor-risk patients with diffuse large B cell lymphoma.  Blood Marrow Transplant. 2014; 20(12):1905-1911.
  10. Gopal AK, Guthrie KA, Rajendran J, et al. 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.
  11. Hertzberg M, Gandhi MK, Trotman J, et al. Early treatment intensification with R-ICE and 90Y-ibritumomab tiuxetan (Zevalin)-BEAM stem cell transplantation in patients with high-risk diffuse large B-cell lymphoma patients and positive interim PET after 4 cycles of R-CHOP-14. Haematologica. 2017; 102(2):356-363.
  12. Illidge TM, Mayes S, Pettengell R, et al. Fractionated 90Y-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.
  13. Illidge TM, McKenzie HS, Mayes S et al. Short duration immunochemotherapy followed by radioimmunotherapy consolidation is effective and well tolerated in relapsed follicular lymphoma: 5-year results from a UK National Cancer Research Institute Lymphoma Group study. Br J Haematol. 2016; 173(2):274-282.
  14. Karmali R, Kassar M, Venugopal P, et al. Safety and efficacy of combination therapy with fludarabine, mitoxantrone, and rituximab followed by yttrium-90 ibritumomab tiuxetan and maintenance rituximab as front-line therapy for patients with follicular or marginal zone lymphoma. Clin Lymphoma Myeloma Leuk. 2011; 11(6):467-474.
  15. 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.
  16. Krishnan A, Nademanee A, Fung HC, et al. Phase II trial of a transplantation regimen of yttrium-90 ibritumomab tiuxetan and high dose chemotherapy in patients with non-Hodgkin’s lymphoma. J Clin Oncol.  2008; 26(1):90-95.
  17. Krishnan A, Palmer JM, 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.
  18. Kulke MH, Siu LL, Tepper JE, et al. Future directions in the treatment of neuroendocrine tumors: consensus report of the National Cancer Institute Neuroendocrine Tumor clinical trials planning meeting. J Clin Oncol.  2011; 29(7):934-943.
  19. Maza SGellrich SAssaf C, et al. Yttrium-90 ibritumomab tiuxetan radioimmunotherapy in primary cutaneous B-cell lymphomas: first results of a prospective, monocentre study. Leuk Lymphoma. 2008; 49(9):1702-1709.
  20. Mei M, Wondergem MJ, Palmer JM, et al. Autologous transplantation for transformed non-Hodgkin lymphoma using an Yttrium-90 ibritumomab tiuxetan conditioning regimen. Biol Blood Marrow Transplant. 2014;20(12):2072-2075.
  21. Morschhauser F, Radford J, Van 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; 28(32):5156-5164.
  22. 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-Line Indolent trial. J Clin Oncol. 2013; 31(16):1977-1983.
  23. Nadamanee A, Forman S, Molina A, et al. A phase 1/2 trial of high-dose yttrium-90-ibritumomab tiuxetan in combination with high-dose etoposide and cyclophosphamide followed by autologous stem cell transplantation in patients with poor-risk or relapsed non-Hodgkin lymphoma. Blood. 2005, 106(8):2896-2902.
  24. 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.
  25. 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.
  26. 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.
  27. Shimoni A, Zwas ST, Oksman Y, et al. Yttrium-90-irbritumomab tiutexan (Zevalin) combined with high-dose BEAM chemotherapy and autologous stem cell transplantation for chemo-refractory aggressive non-Hodgkin’s lymphoma. Exp Hematol. 2007; 35(4):534-540. 
  28. Turaga KK, Kvols LK. Recent progress in the understanding, diagnosis, and treatment of gastroenteropancreatic neuroendocrine tumors. CA Cancer J Clin.  2011; 61(2):113-132.
  29. 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.
  30. 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.
  31. 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):679-686.

Government Agency, Medical Society and Other Authoritative Publications:

  1. Gordon LI, Molina A, Witzig T, et al.  Durable response after ibritumomab tiuxetan radioimmunotherapy for CD20+ B-cell lymphoma: long-term follow-up of a phase I/II study. American Society of Hematology.  Blood.  2004; 103(12):4429-4431.
  2. Henkin RE, Del Rowe JD, Grigsby PW, et al.  ACR-ASTRO Practice guideline for the performance of therapy with unsealed radiopharmaceutical sources.  Clin Nucl Med.  2011; 36(8):e72-e80.
  3. Ibritumomab tiuxetan Monograph. Lexicomp® Online, American Hospital Formulary Service® (AHFS®) Online, Hudson, Ohio, Lexi-Comp., Inc. Last revised July 2, 2012. Accessed on September 29, 2017.
  4. Ibritumomab tiuxetan. NCCN Drugs & Biologics Compendium (NCCN®) © 2017 National Comprehensive Cancer Network, Inc. Available at: Accessed on September 29, 2017.
  5. NCCN Clinical Practice Guidelines in Oncology® (NCCN). © 2017 National Comprehensive Cancer Network, Inc.  Available at: Accessed on: September 29, 2017.
  1. Zevalin [Product Information], Irvine, CA. Spectrum Pharmaceuticals, Inc.  August 30, 2013. Available at: Available at: Accessed on September 29, 2017.
  2. Zevalin (ibritumomab tiuxetan). In: DrugPoints System (electronic version). Truven Health Analytics, Greenwood Village, CO. Updated November 16, 2016. Available at:  Accessed on September 29, 2017.
Websites for Additional Information
  1. American Cancer Society. Available at: Accessed on September 29, 2017.
  2. Leukemia and Lymphoma Society. Ibritumomab Tiuxetan. Available at: Accessed on September 29, 2017.
  3. National Cancer Institute (NCI).  Available at: Accessed on September 29, 2017.
  4. National Cancer Institute.  Targeted cancer therapies: questions and answers. Reviewed April 25, 2014. Available at: Accessed on September 29, 2017.

Ibritumomab Tiuxetan
Non-Hodgkin's Lymphoma (NHL)

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.

Document History
Status Date Action
Reviewed 01/25/2018 Medical Policy & Technology Assessment Committee (MPTAC) review.
Reviewed 01/17/2018 Hematology/Oncology Subcommittee review.



MPTAC review.



Hematology/Oncology Subcommittee review. Updated header language from “Current Effective Date” to “Publish Date.” Updated References and Websites sections.



MPTAC review.



Hematology/Oncology Subcommittee review.  Updated Rationale, References and Websites sections.



MPTAC review



Hematology/Oncology Subcommittee review.  Updated Rationale, References and Website sections. Changed document number from RAD.00031 to THER-RAD.00005. Removed ICD-9 codes from Coding section.



MPTAC review.



Hematology/Oncology Subcommittee review. Removed information regarding the discontinued Bexxar (tositumomab agent). Updated Rationale, Background, References and Website sections.  Updated Coding section to remove HCPCS codes A9544, A9545, G3001 (Bexxar) and A9542 (Zevalin diagnostic no longer part of Zevalin regimen).



MPTAC review.



Hematology/Oncology Subcommittee review. Removed medically necessary indication for Zevalin when used as part of pre-stem cell transplant conditioning regimen.  Added investigational and not medically necessary indication for Zevalin when used as part of pre-stem cell transplant conditioning regimen. Added a note into the Description section about the discontinuation of Bexxar. Updated Rationale, Background, References and Websites sections.



MPTAC review.



Hematology/Oncology Subcommittee review. Clarified CD20 positivity for all medically necessary indications. Clarified investigational and not medically necessary statements. Updated Rationale, Background, References and Websites.



MPTAC review.



Hematology/Oncology Subcommittee review. Added medically necessary indication for pre-autologous transplant conditioning regimen for ibritumomab tiuxetan and tositumomab. Updated Description/Scope, Rationale, Background, References and Websites.



MPTAC review.



Hematology/Oncology Subcommittee review. Rationale and References updated.



MPTAC review.



Hematology/Oncology Subcommittee review. Medically necessary criteria revised to include new FDA approved indications for Zevalin. Rationale and references updated.



Medical Policy & Technology Assessment Committee (MPTAC) review.



Hematology/Oncology Subcommittee review. Background and references updated.



MPTAC review.



Hematology/Oncology Subcommittee review. Transformed B cell NHL removed from ibritumomab tiuxetan (Zevalin®) medically necessary criteria. Rationale and references updated.



MPTAC review. References updated. The phrase “investigational/not medically necessary” was clarified to read “investigational and not medically necessary.” This change was approved at the November 29, 2007 MPTAC meeting.



MPTAC review. References updated.  Coding updated; removed HCPCS A9522, A9523, A9533, A9534 deleted 12/31/2005.



MPTAC review. References updated.



Updated Coding section with 01/01/2006 CPT/HCPCS changes



MPTAC review.  Revision based on Pre-merger Anthem and Pre-merger WellPoint Harmonization. Updated coding: Removed HCPCS code S8002 and S8003 (deleted 01/01/2003)

Pre-Merger Organizations

Last Review Date

Document Number


Anthem, Inc.



Radioimmunotherapy and Somatostatin Receptor Targeted Radiotherapy

WellPoint Health Networks, Inc.


Pharmacology Toolkit

Ibritumomab, Tiuxetan, ZevalinÒ



Pharmacology Toolkit

Tositumomab, Bexxar