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Home , Ibritumomab tiuxetan, Radioimmunotherapy, Tositumomab

MEDICAL POLICY – 8.01.533 in the Treatment of Non-Hodgkin

BCBSA Ref. Policy: 8.01.50 Effective Date: Nov. 1, 2020 RELATED MEDICAL POLICIES: Last Revised: Oct. 13, 2020 2.03.502 Monoclonal for the Treatment of B-Cell Malignancies Replaces: 8.01.524 and 8.01.50

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POLICY CRITERIA | DOCUMENTATION REQUIREMENTS | CODING RELATED INFORMATION | EVIDENCE REVIEW | REFERENCES | HISTORY

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Introduction

When the body detects something that can cause , like a virus or bacteria or a cell, the immune system sends out specific cells to try to destroy the invader. Antibodies connect to harmful molecules. The antibodies act as flags for other immune system cells to attack the harmful molecule. Monoclonal antibodies are made in a lab and are engineered to attach to very specific targets on cancer cells. On some monoclonal antibodies, tiny particles of radiation can be attached. When this radiation-enhanced monoclonal enters the body, it seeks out and links to its target to deliver the radiation. This treatment is known as radioimmunotherapy. This policy describes when radioimmunotherapy may be considered medically necessary.

Note: The Introduction section is for your general knowledge and is not to be taken as policy coverage criteria. The rest of the policy uses specific words and concepts familiar to medical professionals. It is intended for providers. A provider can be a person, such as a doctor, nurse, psychologist, or dentist. A provider also can be a place where medical care is given, like a hospital, clinic, or lab. This policy informs them about when a service may be covered.

Policy Coverage Criteria

Drug Medical Necessity Zevalin® (ibritumomab The use of Zevalin® () may be tiuxetan) considered medically necessary for: • The initial treatment of in patients who are unable to tolerate standard , e.g., elderly or frail patients • Consolidation after chemotherapy for previously untreated CD20-positive follicular non-Hodgkin lymphoma patients who achieve a partial or complete response to first line chemotherapy • A single course of ibritumomab tiuxetan (Zevalin®)for the treatment of relapsed or refractory CD20-positive low-grade , in patients ineligible for high-dose as first line or consolidation of relapse / refractory disease or follicular B-cell non-Hodgkin lymphoma, including patients with refractory non-Hodgkin lymphoma

Drug Investigational Zevalin® (ibritumomab The use of Zevalin® (ibritumomab tiuxetan) is considered tiuxetan) investigational for: • Use as part of a preparatory regimen before autologous or allogeneic hematopoietic stem-cell transplantation in patients with non-Hodgkin lymphoma

Note: Because of the hematologic effects associated with the use of these agents (ie, cytopenias), it is recommended that they not be used in patients with more than 25% bone- marrow involvement by lymphoma and/or in patients with impaired bone-marrow reserve (ie, a count less than 100,000/mm3 or a neutrophil count less than 1,500/mm3).

Documentation Requirements The patient’s medical records submitted for review for all conditions should document that medical necessity criteria are met. The record should include office visit notes that contain the relevant history and physical supporting any of the following:

Page | 2 of 13 ∞ Documentation Requirements • Initial treatment for patient with follicular lymphoma who is unable to tolerate standard chemotherapy (for example, an elderly or frail patient) • Patient has partially or completely responded to the initial chemotherapy for CD20-positive follicular non-Hodgkin lymphoma and needs additional treatment • To be used as a single course for a patient with relapsed or refractory CD20-positive low-grade or follicular B-cell non-Hodgkin lymphoma or mantle cell lymphoma ineligible for high-dose therapy, including patients with rituximab refractory disease

Coding

Code Description CPT 79403 therapy, radiolabeled by intravenous infusion

HCPCS A9542 Indium In-111 ibritumomab tiuxetan, diagnostic, per study dose, up to 5 millicuries

A9543 Yittrium Y-90 ibritumomab tiuxetan, therapeutic, per treatment dose, up to 40 millicuries (Zevalin)

Note: CPT codes, descriptions and materials are copyrighted by the American Medical Association (AMA). HCPCS codes, descriptions and materials are copyrighted by Centers for Medicare Services (CMS).

Related Information

N/A

Evidence Review

Page | 3 of 13 ∞ Description

Radioimmunotherapy (RIT) involves the administration of an antibody linked to a radioisotope, targeted to a specific cell type. Zevalin® (ibritumomab tiuxetan) is a radioimmunoconjugate that targets cell-surface CD20 found on normal B lymphocytes and more than 90% of B-cell non- Hodgkin (NHL).

Background

CD20-based radioimmunotherapy (RIT) for non-Hodgkin lymphoma (NHL) is similar to the anti- CD20 monoclonal antibody rituximab, which is widely used against B-cell malignancies; however, 90Y-ibritumomab tiuxetan uses a monoclonal anti-CD20 antibody to deliver beta- emitting -90.1

RIT offers several advantages over external beam irradiation in the treatment of NHL, a relatively radiosensitive disease.1 RIT is given intravenously and, therefore, normal tissues overlying the tumor are spared significant radiation exposure. RIT provides radiation to known, as well as unsuspected tumor cells and nearby normal cells, producing a ”bystander effect” because the radiation emitted from the isotopes is deposited over several cell diameters with poorly perfused or non--expressing nearby cells within a tumor mass suffering cytotoxic radiation effect.

B-cell and other NHLs can be subdivided into major subcategories as indolent and aggressive. Indolent B-cell lymphomas e.g., follicular lymphoma or small cell lymphocytic lymphoma (SLL) usually present with advanced stage disease (stage IV) and are not considered curable in that stage with current treatments, including chemotherapy or radiotherapy. The disease course is usually prolonged, with a median survival of 7 to 10 years, characterized by initial response to chemotherapy, multiple relapses, and increasing resistance to treatment. In addition, approximately 60% of patients may eventually transform to a more aggressive type of lymphoma. Diffuse large B-cell lymphoma (DLBCL) is the most common aggressive B-cell lymphoma. Although rituximab is widely used in the treatment of B-cell NHL, not all patients respond, and a certain number of patients eventually develop resistance to the drug, necessitating additional treatments after rituximab.

Review articles published in 2010 and 2012 summarized various uses of RIT in NHL, include newly diagnosed disease, recurrent B-cell lymphoma, in combination with chemotherapy or other monoclonal antibodies, as preparative regimen for hematopoietic stem-cell transplant.2,3

Page | 4 of 13 ∞ Summary of Evidence

For individuals with relapsed or refractory low-grade or follicular B-cell non-Hodgkin lymphomas (NHL) who receive ibritumomab tiuxetan, the evidence includes a randomized controlled trial (RCT) and two single-arm studies. Relevant outcomes are overall survival (OS), disease-specific survival, change in disease status, morbid events, quality of life, and treatment- related mortality and morbidity. The RCT showed that ibritumomab tiuxetan resulted in a significantly higher overall response rate of 80% compared with 56% with rituximab alone. Single-arm trials have also demonstrated response rates of 74% to 89% in previously treated disease. The evidence is sufficient to determine that the technology results in a meaningful improvement in the net health outcome.

For individuals who receive initial treatment of follicular B-cell NHL who receive ibritumomab tiuxetan, the evidence includes 4 single-arm studies. Relevant outcomes are OS, disease-specific survival, change in disease status, morbid events, quality of life, and treatment-related mortality and morbidity. The 4 studies have reported high overall response rates ranging from 87% to 94%. However, the median progression-free survival was less than that observed with first-line chemotherapy regimens plus rituximab in other studies. Although RCTs are needed, the current evidence has suggested that ibritumomab may be of clinical value as an initial treatment of indolent NHL, particularly in older, frail patients and that it provides long remissions and results equivalent to multicycle rituximab and chemotherapy combinations. The evidence is sufficient to determine that the technology results in a meaningful improvement in the net health outcome.

For individuals with untreated follicular B-cell NHL who receive ibritumomab tiuxetan as consolidation treatment after remission, the evidence includes a pivotal RCT, a meta-analysis, and 3 single-arm studies. Relevant outcomes are OS, disease-specific survival, change in disease status, morbid events, quality of life, and treatment-related mortality and morbidity. The pivotal RCT demonstrated that consolidation with ibritumomab tiuxetan significantly prolonged median progression-free survival by 23.2 months regardless of partial or complete response after a median follow-up of 3.5 years. The number of patients who died was too small to permit a reliable comparison of survival. Results of the single-arm studies and meta-analysis were directionally consistent with the progression-free survival benefit. The evidence is sufficient to determine that the technology results in a meaningful improvement in the net health outcome.

For individuals with mantle cell lymphoma who are ineligible for high-dose therapy and who receive ibritumomab tiuxetan as part of their first or second-line therapy the evidence consists of several single-arm studies. Relevant outcomes are OS, disease-specific survival, change in disease status, morbid events, quality of life, and treatment-related mortality and morbidity. These studies show an increased CR rate from 41% to a 91% rate, median PFS of 3.3 years and

Page | 5 of 13 ∞ OS of 6.5 years with 30% having DFS at 8 years. The evidence is sufficient to determine that the technology results in a meaningful improvement in the net health outcome.

For individuals with diffuse large B-cell who receive ibritumomab tiuxetan as consolidation treatment after remission, the evidence includes several single-arm studies. Relevant outcomes are OS, disease-specific survival, change in disease status, morbid events, quality of life, and treatment-related mortality and morbidity. Several studies have focused on elderly patients ineligible for stem cell transplantation as post remission therapy. These studies have shown 5- year OS estimates ranging from 83% to 94%. However, whether ibritumomab tiuxetan adds survival benefit over current standard rituximab-containing chemotherapy regimens cannot be determined from these studies. Further, the small samples and lack of data for direct comparison with outcomes of alternative treatments in similar patients preclude firm conclusions. The evidence is insufficient to determine the effects of the technology on health outcomes; therefore, this is considered investigational.

For individuals with chemotherapy-sensitive, relapsed NHL who require hematopoietic cell transplantation and who receive ibritumomab tiuxetan as part of the conditioning regimen, the evidence includes small cohort studies or case series with heterogeneous patient populations and a meta-analysis. Relevant outcomes are OS, disease-specific survival, change in disease status, morbid events, quality of life, and treatment-related mortality and morbidity. Data are promising but evolving; preliminary data have suggested there may be a role for ibritumomab tiuxetan, particularly in patients unable to tolerate potentially curative high-dose chemotherapy and/or total body irradiation because of the risk of excessive treatment-related mortality and morbidity. However, currently, the available data do not support the superiority of conditioning regimens containing ibritumomab tiuxetan over alternative conditioning regimens before hematopoietic cell transplant. RCTs comparing the efficacy and safety of conditioning regimens containing ibritumomab tiuxetan are required. The evidence is insufficient to determine the effects of the technology on health outcomes; therefore, this is considered investigational.

Clinical Input Received from Physician Specialty Societies and Academic Medical Centers

While the various physician specialty societies and academic medical centers may collaborate with and make recommendations during this process, through the provision of appropriate reviewers, input received does not represent an endorsement or position statement by the physician specialty societies or academic medical centers, unless otherwise noted.

Page | 6 of 13 ∞ 2014 Input

In response to requests, input was received from two physician specialty societies, one academic medical center, and three Blue Distinction Centers for Transplant when this policy was under review in 2014. Reviewers unanimously agreed that and ibritumomab tiuxetan were investigational as part of a preparatory regimen before autologous or allogeneic hematopoietic cell transplantation in patients with non-Hodgkin lymphoma (NHL).

2010 Input

In response to requests, input was received from one specialty medical society and one academic medical center and while this policy was under review in 2010. Both reviewers agreed that tositumomab was medically necessary for relapsed or rituximab-refractory follicular lymphoma and that use of ibritumomab tiuxetan would be medically necessary for relapsed or refractory NHL, although one reviewer questioned the use of ibritumomab tiuxetan in lymphoma transformed to diffuse large B-cell lymphoma. Both reviewers indicated that there is a role for radioimmunotherapy in the initial treatment of indolent NHL, particularly in older, frail patients and that it provides long remissions and results equivalent to multicycle rituximab and chemotherapy combinations. Both reviewers indicated that radioimmunotherapy is medically necessary as consolidation therapy, and both agreed that there conditioning regimens are beneficial role before hematopoietic cell transplantation.

Practice Guidelines and Position Statements

National Comprehensive Cancer Network (NCCN)

NCCN practice guidelines (V 5.2019)51 make the following recommendations for radioimmunotherapy (RIT) in non-Hodgkin lymphoma (NHL):

• Follicular lymphoma (These guidelines apply to patients with histological grade 1 or 2 follicular lymphoma; grade 3 follicular lymphoma is commonly treated like diffuse large B- cell lymphoma.)

o As first-line therapy for elderly or infirm if other first-line are not tolerable (category 2B)

Page | 7 of 13 ∞ o As first-line consolidation after induction with chemotherapy or chemoimmunotherapy (category 2B)

• For histologic transformation of follicular lymphoma to diffuse large B-cell lymphoma, either after multiple prior therapies, or after minimal or no prior chemotherapy if initial treatment for transformed disease yields only partial response, no response, or progressive disease RIT (category 2B)

• Primary Cutaneous Diffuse Large B-Cell Lymphoma, leg type

o As secondary therapy for generalized (skin-only) disease (stage T3) that either has relapsed or only partially responded to initial therapy (category 2B).

National Comprehensive Cancer Network guidelines do not list RIT among its recommended primary or secondary treatments for any other type of B-cell NHL (e.g., de novo diffuse large B- cell or mantle cell lymphomas).51

Medicare National Coverage

There is no national coverage determination.

Regulatory Status

In 2002, ibritumomab tiuxetan (Zevalin®) was granted accelerated approval by the U.S. Food and Drug Administration (FDA) for the treatment of patients with relapsed or refractory low- grade, follicular or transformed B-cell NHL, including patients with rituximab-refractory follicular NHL. In March 2008, the indication for transformed B-cell NHL was removed.4 In 2009, FDA approved ibritumomab tiuxetan (Zevalin®) for consolidation therapy in previously untreated follicular NHL in patients who achieve a partial or complete response to first-line chemotherapy. Current FDA-approved indications are (1) relapsed or refractory, low-grade or follicular B-cell NHL and (2) previously untreated follicular NHL in patients who achieve a partial or complete response to first-line chemotherapy.5

In 2003, tositumomab (Bexxar®) was approved by FDA for rituximab-refractory follicular NHL. In February 2014, GlaxoSmithKline discontinued the manufacture and sale of tositumomab (Bexxar®).6

Page | 8 of 13 ∞ References

1. Emmanouilides C. Radioimmunotherapy for non-hodgkin lymphoma : historical perspective and current status. J Clin Exp Hematop. Nov 2007;47(2):43-60. PMID 18040144

2. Palanca-Wessels MC, Press OW. Improving the efficacy of radioimmunotherapy for non-Hodgkin lymphomas. Cancer. Feb 15 2010;116(4 Suppl):1126-1133. PMID 20127945

3. Stevens PL, Oluwole O, Reddy N. Advances and application of radioimmunotherapy in non-Hodgkin lymphoma. Am J Blood Res. 2012;2(2):86-97. PMID 22762027

4. Food and Drug Administration. Letter to Biogen Idec, Inc. March 25, 2008. https://www.accessdata.fda.gov/drugsatfda_docs/appletter/2008/125104s0033ltr.pdf. Accessed October, 2020.

5. , Inc. Zevalin® (ibritumomab tiuxetan) injection for intravenous use prescribing information, August 2013. http://www.zevalin.com/. Accessed October, 2020.

6. GlaxoSmithKline. Press release archive. GSK to discontinue manufacture and sale of the Bexxar® therapeutic regimen (tositumomab and iodine I-131 tositumomab) - August 2013.

7. 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. Aug 01 2002;20(15):3262-3269. PMID 12149300

8. 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. May 15 2002;20(10):2453-2463. PMID 12011122

9. 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. Sep 2004;5(2):98-101. PMID 15453924

10. Scholz CW, Pinto A, Linkesch W, et al. (90)Yttrium-ibritumomab-tiuxetan as first-line treatment for follicular lymphoma: 30 months of follow-up data from an international multicenter phase II . J Clin Oncol. Jan 20 2013;31(3):308-313. PMID 23233718

11. 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. Mar 2014;164(5):710-716. PMID 24344981

12. 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. Jan 20 2014;32(3):212-218. PMID 24297953

13. 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(suppl 2):17-29. PMID 19819921

14. Emmanouilides C. Review of Y-ibritumomab tiuxetan as first-line consolidation radio-immunotherapy for B-cell follicular non- Hodgkin's lymphoma. Cancer Manag Res. Oct 21 2009;1:131-136. PMID 21188131

15. Forstpointner R, Dreyling M. Rituximab maintenance versus radioimmunotherapy consolidation in follicular lymphoma: which, when, and for whom? Curr Hematol Malig Rep. Dec 2011;6(4):207-215. PMID 21909660

16. 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. Dec 2012;12(6):393-399. PMID 23158095

17. 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. Nov 10 2008;26(32):5156-5164. PMID 18854568

Page | 9 of 13 ∞ 18. Press OW. Evidence mounts for the efficacy of radioimmunotherapy for B-cell lymphomas. J Clin Oncol. Nov 10 2008;26(32):5147-5150. PMID 18854559

19. 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. Jun 01 2013;31(16):1977-1983. PMID 23547079

20. 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. Nov 01 2008;14(21):7088-7094. PMID 18981007

21. 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 Group. Leuk Lymphoma. Jan 2014;55(1):51-55. PMID 23573825

22. Tomblyn M. Radioimmunotherapy for B-cell non-hodgkin lymphomas. Cancer Control. Jul 2012;19(3):196-203. PMID 22710895

23. 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. Apr 2008;19(4):769-773. PMID 18303033

24. 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. Aug 1 2010;16(15):3998-4004. PMID 20542986

25. 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. Jul 1 2007;110(1):54- 58. PMID 17387223

26. 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. Aug 2014;41(8):1585-1592. PMID 24722703

27. 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. Jan 8 2015;125(2):236-241. PMID 25395425

28. 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. Sep 2015;170(5):679-686. PMID 25974212

29. 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. Sep 1 2012;30(25):3119-3126. PMID 22851557

30. Kluin-Nelemans JC, Hoster E, Walewski J, et al. R-CHOP versus R-FC followed by maintenance with rituximab versus interferon- alfa: Outcome of the first randomized trial for elderly patients with mantle cell lymphoma. Blood 118, 2011 (abstr 439). http://www.bloodjournal.org/content/118/21/439?sso-checked=true. Accessed October, 2020.

31. Kluin-Nelemans HC, Hoster E, Hermine O, et al. Treatment of older patients with mantle-cell lymphoma. N Engl J Med. Aug 09 2012;367(6):520-531. PMID 22873532

32. 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(suppl 2):41-51. PMID 19819923

33. 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. Nov 10 2008;26(32):5175-5182. PMID 18854569

34. Vose JM, Bierman PJ, Enke C, et al. Phase I trial of iodine-131 tositumomab with high-dose chemotherapy and autologous stem-cell transplantation for relapsed non-Hodgkin's lymphoma. J Clin Oncol. Jan 20 2005;23(3):461-467. PMID 15534357

Page | 10 of 13 ∞ 35. 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. Aug 10 2013;31(23):2974-2976. PMID 23857974

36. 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. Oct 01 2012;118(19):4706-4714. PMID 22252613

37. Krishnan A, Palmer JM, Tsai NC, 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. Mar 2012;18(3):441-450. PMID 21801706

38. 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. Jun 2012;47(2):119-125. PMID 22783358

39. 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. Sep 2011;90(9):1075-1082. PMID 21336624

40. 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. Jun 2011;52(6):891-895. PMID 21571787

41. 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. Mar 2014;99(3):505-510. PMID 24162789

42. 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. May 8 2014;123(19):2953-2959. PMID 24652994

43. 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. Aug 2014;3(4):927-938. PMID 24740968

44. Shimoni A, Zwas ST, 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. Feb 2008;41(4):355-361. PMID 18026153

45. 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. Sep 09 2010;116(10):1795-1802. PMID 20530284

46. 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. Jul 28 2011;118(4):1132-1139. PMID 21508413

47. 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. Dec 2011;46(12):1503-1509. PMID 21258420

48. 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. Jun 28 2012;119(26):6373-6378. PMID 22586182

49. 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. Nov 2012;47(11):1397-1402. PMID 22504934

50. 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. Jan 2015;26(1):193-198. PMID 25361987

Page | 11 of 13 ∞ 51. National Comprehensive Cancer Network (NCCN). NCCN Clinical Practice Guidelines in Oncology: B-cell Lymphomas. Version 5.2019 Available at: https://www.nccn.org/professionals/physician_gls/pdf/b-cell.pdf. Accessed October, 2020.

52. Frederick Lansigan, et al. Multicenter, Open-Label, Phase II Study of and Rituximab followed by 90-Yttrium (Y) Ibritumomab Tiuxetan for Untreated Follicular Lymphoma (FOL-BRITe). Clinical cancer Res 2019 Oct 15;25(20):6073-6079

53. Wojciech Jurczak, et al. Consolidation with 90 Y ibritumomab tiuxetan radioimmunotherapy in mantle cell lymphoma patients ineligible for high-dose therapy: results of the phase II multicenter Polish Lymphoma Research Group Trial, after 8-year long follow-up. Leuk Lymphoma 2019 Nov;60(10):2689-2696.

History

Date Comments 10/14/13 New policy. Policy approved with medically necessary indications for non-Hodgkin lymphoma when utilized as outlines. Policy replaces 8.01.524 which is now deleted.

07/14/14 Annual Review. Policy updated with literature review on April 16, 2014. Clinical input reviewed. Rationale reorganized and references renumbered. References 4, 10, and 50 updated; references 5, 12-14, 24-25, 31-32, 35-36, 43 added. Policy statements reorganized and updated to reflect discontinuation of tositumomab and current FDA labeling of ibritumomab tiuxetan. Policy renumbered to 8.01.533.

07/14/15 Annual Review. Policy updated with literature search; no change to policy statement. References updated.

10/13/15 Annual Review. Policy updated with literature review; no change in policy statements.

12/01/16 Annual Review, approved November 8, 2016. No changes to policy statement.

10/01/17 Annual Review, approved September 5, 2017. Policy updated with literature review through June 2, 2017; references 9 and 19 added; no change in policy statements.

10/01/18 Annual Review, approved September 20, 2018. No changes to policy statement.

11/01/19 Annual Review, approved October 4, 2019. Policy updated to reflect current NCCN guidelines, no changes to policy statements.

11/01/20 Annual Review, approved October 13, 2020. Policy statement changed for Mantle Cell lymphoma patients that are ineligible for high-dose therapy. References updated, no other changes to policy statements.

Disclaimer: This medical policy is a guide in evaluating the medical necessity of a particular service or treatment. The Company adopts policies after careful review of published peer-reviewed scientific literature, national guidelines and local standards of practice. Since medical technology is constantly changing, the Company reserves the right to review and update policies as appropriate. Member contracts differ in their benefits. Always consult the member benefit booklet or contact a member service representative to determine coverage for a specific medical service or supply.

Page | 12 of 13 ∞ CPT codes, descriptions and materials are copyrighted by the American Medical Association (AMA). ©2020 Premera All Rights Reserved.

Scope: Medical policies are systematically developed guidelines that serve as a resource for Company staff when determining coverage for specific medical procedures, drugs or devices. Coverage for medical services is subject to the limits and conditions of the member benefit plan. Members and their providers should consult the member benefit booklet or contact a customer service representative to determine whether there are any benefit limitations applicable to this service or supply. This medical policy does not apply to Medicare Advantage.

Page | 13 of 13 ∞

Discrimination is Against the Law Oromoo (Cushite): Beeksisni kun odeeffannoo barbaachisaa qaba. Beeksisti kun sagantaa Premera Blue Cross complies with applicable Federal civil rights laws and yookan karaa Premera Blue Cross tiin tajaajila keessan ilaalchisee does not discriminate on the basis of race, color, national origin, age, odeeffannoo barbaachisaa qabaachuu danda’a. Guyyaawwan murteessaa disability, or sex. Premera does not exclude people or treat them differently ta’an beeksisa kana keessatti ilaalaa. Tarii kaffaltiidhaan deeggaramuuf because of race, color, national origin, age, disability or sex. yookan tajaajila fayyaa keessaniif guyyaa dhumaa irratti wanti raawwattan jiraachuu danda’a. Kaffaltii irraa bilisa haala ta’een afaan keessaniin Premera: odeeffannoo argachuu fi deeggarsa argachuuf mirga ni qabaattu. • Provides free aids and services to people with disabilities to communicate Lakkoofsa bilbilaa 800-722-1471 (TTY: 800-842-5357) tii bilbilaa. effectively with us, such as: • Qualified sign language interpreters Français (French): • Written information in other formats (large print, audio, accessible Cet avis a d'importantes informations. Cet avis peut avoir d'importantes electronic formats, other formats) informations sur votre demande ou la couverture par l'intermédiaire de • Provides free language services to people whose primary language is not Premera Blue Cross. Le présent avis peut contenir des dates clés. Vous English, such as: devrez peut-être prendre des mesures par certains délais pour maintenir votre couverture de santé ou d'aide avec les coûts. Vous avez le droit • Qualified interpreters d'obtenir cette information et de l’aide dans votre langue à aucun coût. • Information written in other languages Appelez le 800-722-1471 (TTY: 800-842-5357).

If you need these services, contact the Civil Rights Coordinator. Kreyòl ayisyen (Creole):

Avi sila a gen Enfòmasyon Enpòtan ladann. Avi sila a kapab genyen If you believe that Premera has failed to provide these services or enfòmasyon enpòtan konsènan aplikasyon w lan oswa konsènan kouvèti discriminated in another way on the basis of race, color, national origin, age, asirans lan atravè Premera Blue Cross. Kapab genyen dat ki enpòtan nan disability, or sex, you can file a grievance with: avi sila a. Ou ka gen pou pran kèk aksyon avan sèten dat limit pou ka Civil Rights Coordinator - Complaints and Appeals kenbe kouvèti asirans sante w la oswa pou yo ka ede w avèk depans yo. PO Box 91102, Seattle, WA 98111 Se dwa w pou resevwa enfòmasyon sa a ak asistans nan lang ou pale a, Toll free 855-332-4535, Fax 425-918-5592, TTY 800-842-5357 san ou pa gen pou peye pou sa. Rele nan 800-722-1471 Email [email protected] (TTY: 800-842-5357).

You can file a grievance in person or by mail, fax, or email. If you need help Deutsche (German): filing a grievance, the Civil Rights Coordinator is available to help you. Diese Benachrichtigung enthält wichtige Informationen. Diese

Benachrichtigung enthält unter Umständen wichtige Informationen You can also file a civil rights complaint with the U.S. Department of Health bezüglich Ihres Antrags auf Krankenversicherungsschutz durch Premera and Human Services, Office for Civil Rights, electronically through the Blue Cross. Suchen Sie nach eventuellen wichtigen Terminen in dieser Office for Civil Rights Complaint Portal, available at Benachrichtigung. Sie könnten bis zu bestimmten Stichtagen handeln https://ocrportal.hhs.gov/ocr/portal/lobby.jsf, or by mail or phone at: müssen, um Ihren Krankenversicherungsschutz oder Hilfe mit den Kosten U.S. Department of Health and Human Services zu behalten. Sie haben das Recht, kostenlose Hilfe und Informationen in 200 Independence Avenue SW, Room 509F, HHH Building Ihrer Sprache zu erhalten. Rufen Sie an unter 800-722-1471 Washington, D.C. 20201, 1-800-368-1019, 800-537-7697 (TDD) (TTY: 800-842-5357). Complaint forms are available at http://www.hhs.gov/ocr/office/file/index.html. Hmoob (Hmong):

Tsab ntawv tshaj xo no muaj cov ntshiab lus tseem ceeb. Tej zaum Getting Help in Other Languages tsab ntawv tshaj xo no muaj cov ntsiab lus tseem ceeb txog koj daim ntawv thov kev pab los yog koj qhov kev pab cuam los ntawm Premera Blue This Notice has Important Information. This notice may have important Cross. Tej zaum muaj cov hnub tseem ceeb uas sau rau hauv daim ntawv information about your application or coverage through Premera Blue no. Tej zaum koj kuj yuav tau ua qee yam uas peb kom koj ua tsis pub Cross. There may be key dates in this notice. You may need to take action dhau cov caij nyoog uas teev tseg rau hauv daim ntawv no mas koj thiaj by certain deadlines to keep your health coverage or help with costs. You yuav tau txais kev pab cuam kho mob los yog kev pab them tej nqi kho mob have the right to get this information and help in your language at no cost. ntawd. Koj muaj cai kom lawv muab cov ntshiab lus no uas tau muab sau Call 800-722-1471 (TTY: 800-842-5357). ua koj hom lus pub dawb rau koj. Hu rau 800-722-1471 (TTY: 800-842-5357). አማሪኛ (Amharic): ይህ ማስታወቂያ አስፈላጊ መረጃ ይዟል። ይህ ማስታወቂያ ስለ ማመልከቻዎ ወይም የ Premera Blue Iloko (Ilocano): Cross ሽፋን አስፈላጊ መረጃ ሊኖረው ይችላል። በዚህ ማስታወቂያ ውስጥ ቁልፍ ቀኖች ሊኖሩ ይችላሉ። Daytoy a Pakdaar ket naglaon iti Napateg nga Impormasion. Daytoy a የጤናን ሽፋንዎን ለመጠበቅና በአከፋፈል እርዳታ ለማግኘት በተውሰኑ የጊዜ ገደቦች እርምጃ መውሰድ pakdaar mabalin nga adda ket naglaon iti napateg nga impormasion

ይገባዎት ይሆናል። ይህን መረጃ እንዲያገኙ እና ያለምንም ክፍያ በቋንቋዎ እርዳታ እንዲያገኙ መብት maipanggep iti apliksayonyo wenno coverage babaen iti Premera Blue አለዎት።በስልክ ቁጥር 800-722-1471 (TTY: 800-842-5357) ይደውሉ። Cross. Daytoy ket mabalin dagiti importante a petsa iti daytoy a pakdaar. Mabalin nga adda rumbeng nga aramidenyo nga addang sakbay dagiti Arabic): partikular a naituding nga aldaw tapno mapagtalinaedyo ti coverage ti) العربية salun-atyo wenno tulong kadagiti gastos. Adda karbenganyo a mangala iti يحوي ھذا اإلشعار معلومات ھامة . قد يحوي ھذا اإلشعار معلومات مھمة بخصوص طلبك أو daytoy nga impormasion ken tulong iti bukodyo a pagsasao nga awan ti التغطية التي تريد الحصول عليھا من خالل Premera Blue Cross. قد تكون ھناك تواريخ مھمة .(bayadanyo. Tumawag iti numero nga 800-722-1471 (TTY: 800-842-5357 في ھذا اإلشعار . وقد تحتاج التخاذ إجراء في تواريخ معينة للحفاظ على تغطيتك الصحية أو للمساعدة في دفع التكاليف . يحق لك الحصول على ھذه المعلومات والمساعدة بلغتك دون تكبد أية تكلفة . اتصل :(Italiano (Italian بـ(TTY: 800-842-5357) 800-722-1471 Questo avviso contiene informazioni importanti. Questo avviso può contenere 中文 (Chinese): informazioni importanti sulla tua domanda o copertura attraverso Premera 本通知有重要的訊息。 本通知可能有關於您透過 Premera Blue Cross 提交的 Blue Cross. Potrebbero esserci date chiave in questo avviso. Potrebbe 申請或保險的重要訊息。本通知內可能有重要日期。您可能需要在截止日期 essere necessario un tuo intervento entro una scadenza determinata per 之前採取行動，以保留您的健康保險或者費用補貼。您有權利免費以您的母 consentirti di mantenere la tua copertura o sovvenzione. Hai il diritto di ottenere queste informazioni e assistenza nella tua lingua gratuitamente. 語得到本訊息和幫助。請撥電話 。 800-722-1471 (TTY: 800-842-5357) Chiama 800-722-1471 (TTY: 800-842-5357).

037338 (07-2016) 日本語 (Japanese): Română (Romanian): この通知には重要な情報が含まれています。この通知には、 Premera Blue Prezenta notificare conține informații importante. Această notificare Cross の申請または補償範囲に関する重要な情報が含まれている場合があ poate conține informații importante privind cererea sau acoperirea asigurării ります。この通知に記載されている可能性がある重要な日付をご確認くだ dumneavoastre de sănătate prin Premera Blue Cross. Pot exista date cheie în aceast notificare. Este posibil s fie nevoie s ac iona i pân la anumite さい。健康保険や有料サポートを維持するには、特定の期日までに行動を ă ă ă ț ț ă termene limită pentru a vă menține acoperirea asigurării de sănătate sau 取らなければならない場合があります。ご希望の言語による情報とサポー asistența privitoare la costuri. Aveți dreptul de a obține gratuit aceste トが無料で提供されます。800-722-1471 (TTY: 800-842-5357)までお電話 informații și ajutor în limba dumneavoastră. Sunați la 800-722-1471 ください。 (TTY: 800-842-5357).

한국어 (Korean): Pусский (Russian): 본 통지서에는 중요한 정보가 들어 있습니다 . 즉 이 통지서는 귀하의 신청에 Настоящее уведомление содержит важную информацию. Это 관하여 그리고 Premera Blue Cross 를 통한 커버리지에 관한 정보를 уведомление может содержать важную информацию о вашем Premera Blue Cross. 포함하고 있을 수 있습니다 . 본 통지서에는 핵심이 되는 날짜들이 있을 수 заявлении или страховом покрытии через В настоящем уведомлении могут быть указаны ключевые даты. Вам, 있습니다. 귀하는 귀하의 건강 커버리지를 계속 유지하거나 비용을 절감하기 возможно, потребуется принять меры к определенным предельным 위해서 일정한 마감일까지 조치를 취해야 할 필요가 있을 수 있습니다 . срокам для сохранения страхового покрытия или помощи с расходами. 귀하는 이러한 정보와 도움을 귀하의 언어로 비용 부담없이 얻을 수 있는 Вы имеете право на бесплатное получение этой информации и 권리가 있습니다 . 800-722-1471 (TTY: 800-842-5357) 로 전화하십시오 . помощь на вашем языке. Звоните по телефону 800-722-1471 (TTY: 800-842-5357). ລາວ (Lao): Fa’asamoa (Samoan): ້ ້ ້ ້ ແຈ້ງການນີ ມີ ຂໍ ມູ ນສໍ າຄັ ນ. ແຈ້ງການນີ ອາດຈະມີ ຂໍ ມູ ນສໍ າຄັ ນກ່ ຽວກັບຄໍ າຮ້ອງສະ Atonu ua iai i lenei fa’asilasilaga ni fa’amatalaga e sili ona taua e tatau ໝັ ກ ຫືຼ ຄວາມຄຸ້ ມຄອງປະກັນໄພຂອງທ່ານຜ່ານ Premera Blue Cross. ອາດຈະມີ ona e malamalama i ai. O lenei fa’asilasilaga o se fesoasoani e fa’amatala ວັນທີ ສໍ າຄັ ນໃນແຈ້ງການນີ້ . ທ່ານອາດຈະຈໍ າເປັ ນຕ້ອງດໍ າເນີ ນການຕາມກໍ ານົ ດ atili i ai i le tulaga o le polokalame, Premera Blue Cross, ua e tau fia maua ເວລາສະເພາະເພື່ ອຮັກສາຄວາມຄຸ້ ມຄອງປະກັນສຸ ຂະພາບ ຫືຼ ຄວາມຊ່ວຍເຫືຼ ອເລື່ ອງ atu i ai. Fa’amolemole, ia e iloilo fa’alelei i aso fa’apitoa olo’o iai i lenei fa’asilasilaga taua. Masalo o le’a iai ni feau e tatau ona e faia ao le’i aulia le ້ ້ ຄ່ າໃຊ້ຈ່າຍຂອງທ່ານໄວ້ . ທ່ານມີ ສິ ດໄດ້ ຮັບຂໍ ມູ ນນີ ແລະ ຄວາມຊ່ວຍເຫືຼ ອເປັ ນພາສາ aso ua ta’ua i lenei fa’asilasilaga ina ia e iai pea ma maua fesoasoani mai ai ຂອງທ່ານໂດຍບໍ່ ເສຍຄ່ າ. ໃຫ້ໂທຫາ 800-722-1471 (TTY: 800-842-5357). i le polokalame a le Malo olo’o e iai i ai. Olo’o iai iate oe le aia tatau e maua atu i lenei fa’asilasilaga ma lenei fa’matalaga i legagana e te malamalama i 徶羶ែខមរ (Khmer): ai aunoa ma se togiga tupe. Vili atu i le telefoni 800-722-1471 (TTY: 800-842-5357). េសចកតជី ូនដណំ ឹងេនះ掶នព័ត៌掶ន架៉ ងស޶នំ។ ់ េសចកតីជូនដំណឹងេនះរបែហល ᾶ掶នព័ត៌掶ន架៉ ងសំ޶ន់អពំ ីទរមង់ ែបបបទ ឬζរ殶៉ បរង់ របសអ់ នក㾶មរយៈ Español (Spanish): Premera Blue Cross ។ របែហលᾶ掶ន ζលបរ េចិ ឆទសំ޶ន់េ俅កន ុងេសចកតជី ូន Este Aviso contiene información importante. Es posible que este aviso contenga información importante acerca de su solicitud o cobertura a ដណំ ងេនះ។ឹ អនករបែហលᾶរតវζរបេញូ ច ញសមត徶ពថ ដលក់ ណតំៃថ ់ ងᾶកច厶់ ស់ través de Premera Blue Cross. Es posible que haya fechas clave en este 侶侶 េដើមបីនងរកឹ 羶ទកζរ䮶侶ុ 殶៉ បរង់ សខ徶ពរបសុ ់អនក ឬរ厶កជ់ ំនួយេចញៃថល។ aviso. Es posible que deba tomar alguna medida antes de determinadas អនក掶នសទិ ធទទិ ួលព័ត掶នេ៌ នះ និងជំនួយេ俅កន ុង徶羶របស់អនកេ⮶យមនអសិ fechas para mantener su cobertura médica o ayuda con los costos. Usted លយេឡុ ើយ។ សូ មទូរស័ពទ 800-722-1471 (TTY: 800-842-5357)។ tiene derecho a recibir esta información y ayuda en su idioma sin costo alguno. Llame al 800-722-1471 (TTY: 800-842-5357).

ਪ ੰ ਜਾਬੀ (Punjabi): Tagalog (Tagalog): ਇਸ ਨ ੋ ਿਟਸ ਿਵਚ ਖਾਸ ਜਾਣਕਾਰੀ ਹੈ. ਇਸ ਨ ੋ ਿਟਸ ਿਵਚ Premera Blue Cross ਵਲ ƒ ਤੁਹਾਡੀ Ang Paunawa na ito ay naglalaman ng mahalagang impormasyon. Ang paunawa na ito ay maaaring naglalaman ng mahalagang impormasyon ਕਵਰਜੇ ਅਤ ੇ ਅਰਜੀ ਬਾਰ ੇ ਮਹ ੱ ਤਵਪਰਨੂ ਜਾਣਕਾਰੀ ਹ ੋ ਸਕਦੀ ਹ ੈ . ਇਸ ਨ ੋ ਿਜਸ ਜਵਚ ਖਾਸ ਤਾਰੀਖਾ . tungkol sa iyong aplikasyon o pagsakop sa pamamagitan ng Premera Blue ਹੋ ਸਕਦੀਆਂ ਹਨ ਜੇਕਰ ਤਸੀੁ ਜਸਹਤ ਕਵਰਜੇ ਿਰੱ ਖਣੀ ਹਵੋ ੇ ਜਾ ਓਸ ਦੀ ਲਾਗਤ ਜਿਵੱ ਚ ਮਦਦ ਦੇ Cross. Maaaring may mga mahalagang petsa dito sa paunawa. Maaring ਇਛ ੱ ੁਕ ਹ ੋ ਤ拓 ਤਹਾਨ ੁ ੰ ੂ ਅ ੰ ਤਮ ਤਾਰੀਖ਼ ਤ ƒ ਪਿਹਲ拓 ਕੁੱ ਝ ਖਾਸ ਕਦਮ ਚੱ ਕਣ ੁ ਦੀ ਲੋੜ ਹ ੋ ਸਕਦੀ ਹ ੈ ,ਤੁਹਾਨੰ ੂ mangailangan ka na magsagawa ng hakbang sa ilang mga itinakdang ਮਫ਼ਤੁ ਿਵੱ ਚ ਤ ੇ ਆਪਣੀ ਭਾਸ਼ਾ ਿਵ ੱ ਚ ਜਾਣਕਾਰੀ ਅਤ ੇ ਮਦਦ ਪਾਪਤ㘰 ਕਰਨ ਦਾ ਅਿਧਕਾਰ ਹੈ ,ਕਾਲ panahon upang mapanatili ang iyong pagsakop sa kalusugan o tulong na 800-722-1471 (TTY: 800-842-5357). walang gastos. May karapatan ka na makakuha ng ganitong impormasyon at tulong sa iyong wika ng walang gastos. Tumawag sa 800-722-1471 .(Farsi): (TTY: 800-842-5357) فارسی اين اعالميه حاوی اطالعات مھم ميباشد .اين اعالميه ممکن است حاوی اطالعات مھم درباره فرم :(ไทย (Thai تقاضا و يا پ وشش بيمه ای شما از طريق Premera Blue Cross باشد . به تاريخ ھای مھم در ั ประกาศนมข้ี ี ้อมลส ู ําคญ ั ประกาศนอาจม ้ี ีข ้อมลท ู ่ีส ําคญเก ั ่ียวกบการการสม ัครหร ั ือขอบเขตประกน اين اعالميه توجه نماييد .شما ممکن است برای حقظ پوشش بيمه تان يا کمک در پرداخت ھزينه . สขภาพของคุณผ ุาน ่ Premera Blue Cross และอาจมีก ําหนดการในประกาศนี ้ คณอาจจะต ุ ้อง ھای درمانی تان، به تاريخ ھای مشخصی برای انجام کارھای خاصی احتياج داشته باشيد شما حق اين را داريد که اين اطالعات و ک مک را به زبان خود به طور رايگان دريافت نماييد . برای کسب ี่ ดําเน ินการภายในกาหนดระยะเวลาท ํ ่ีแนนอนเพ ่ ่ือจะร ักษาการประกนส ัขภาพของค ุณหร ุ ือการช ่วยเหล ือท اطالعات با شماره 1471-722-800 (کاربران TTY تماس باشماره 5357-842-800) تماس มคี่้่าใชจาย คณม ุีิิ่ี้ัู้สทธทจะไดรบขอมลและความชวยเหล ่ ื้ีอนในภาษาของคณโดยไม ุ่มค ี่้่าใชจาย โทร برقرار نماييد . 800-722-1471 (TTY: 800-842-5357) Polskie (Polish): To og oszenie mo e zawiera wa ne informacje. To og oszenie mo e ł ż ć ż ł ż Український (Ukrainian): zawiera wa ne informacje odno nie Pa stwa wniosku lub zakresu ć ż ś ń Це повідомлення містить важливу інформацію. Це повідомлення świadczeń poprzez Premera Blue Cross. Prosimy zwrócic uwagę na може містити важливу інформацію про Ваше звернення щодо kluczowe daty, które mogą być zawarte w tym ogłoszeniu aby nie страхувального покриття через Premera Blue Cross. Зверніть увагу на przekroczyć terminów w przypadku utrzymania polisy ubezpieczeniowej lub ключові дати, які можуть бути вказані у цьому повідомленні. Існує pomocy zwi zanej z kosztami. Macie Pa stwo prawo do bezp atnej ą ń ł імовірність того, що Вам треба буде здійснити певні кроки у конкретні informacji we własnym języku. Zadzwońcie pod 800-722-1471 кінцеві строки для того, щоб зберегти Ваше медичне страхування або (TTY: 800-842-5357). отримати фінансову допомогу. У Вас є право на отримання цієї

інформації та допомоги безкоштовно на Вашій рідній мові. Дзвоніть за Português (Portuguese): номером телефону 800-722-1471 (TTY: 800-842-5357). Este aviso contém informações importantes. Este aviso poderá conter informações importantes a respeito de sua aplicação ou cobertura por meio Tiếng Việt (Vietnamese): do Premera Blue Cross. Poderão existir datas importantes neste aviso. Thông báo này cung cấp thông tin quan trọng. Thông báo này có thông Talvez seja necessário que você tome providências dentro de tin quan trọng về đơn xin tham gia hoặc hợp đồng bảo hiểm của quý vị qua determinados prazos para manter sua cobertura de saúde ou ajuda de chương trình Premera Blue Cross. Xin xem ngày quan trọng trong thông custos. Você tem o direito de obter esta informação e ajuda em seu idioma báo này. Quý vị có thể phải thực hiện theo thông báo đúng trong thời hạn e sem custos. Ligue para 800-722-1471 (TTY: 800-842-5357). để duy trì bảo hiểm sức khỏe hoặc được trợ giúp thêm về chi phí. Quý vị có quyền được biết thông tin này và được trợ giúp bằng ngôn ngữ của mình miễn phí. Xin gọi số 800-722-1471 (TTY: 800-842-5357).