MEDICAL POLICY – 2.03.01

In Vitro Chemoresistance and Chemosensitivity Assays

BCBSA Ref. Policy: 2.03.01

Effective Date: Oct. 1, 2019

Last Revised: Jan. 1, 2020

Replaces: N/A

RELATED MEDICAL POLICIES:

None

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POLICY CRITERIA | CODING | RELATED INFORMATION

EVIDENCE REVIEW | REFERENCES | HISTORY

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Introduction

Chemotherapy is the use of drugs to try to kill cancer cells. Assays (laboratory tests) have been

created to try to find out if a person’s cancer might respond to or will resist specific

chemotherapy drugs. Cells removed from the tumor during surgery or a biopsy are tested in a

lab to see if they react to different chemotherapy drugs. High quality research studies don’t yet

show whether these tests improve treatment results. For this reason chemoresistance and

chemosensitivity lab tests are considered unproven (investigational).

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

Assay Investigational In vitro chemosensitivity

assays

In vitro chemosensitivity assays are considered investigational,

including, but not limited to:

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Assay Investigational • The Histoculture Drug Response Assay

• A fluorescent cytoprint assay

• The ChemoFx assay

In vitro chemoresistance

assays

In vitro chemoresistance assays are considered investigational,

including, but not limited to:

• Extreme Drug Resistance assays

Coding

Code Description

CPT 0564T Oncology, chemotherapeutic drug cytotoxicity assay of cancer stem cells (cscs), from

cultured cscs and primary tumor cells, categorical drug response reported based on

percent of cytotoxicity observed, a minimum of 14 drugs or drug combinations (new

code effective 1/1/20)

81535 Oncology (gynecologic), live tumor cell culture and chemotherapeutic response by

DAPI stand and morphology, predictive algorithm reported as a drug response score;

first single drug or drug combination

(applies to ChemoFX®)

81536 Oncology (gynecologic), live tumor cell culture and chemotherapeutic response by

DAPI stain and morphology, predictive algorithm reported as a drug response score;

each additional single drug or drug combination (List separately in addition to code

for primary procedure))

(applies to ChemoFX®)

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

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Evidence Review

Description

In vitro chemoresistance and chemosensitivity assays have been developed to provide

information about the characteristics of an individual patient’s malignancy to predict potential

responsiveness of their cancer to specific drugs. Oncologists may sometimes use these assays to

select treatment regimens for a patient. Several assays have been developed that differ

concerning the processing of biologic samples and detection methods. However, all involve

similar principles and share protocol components including: (1) isolation of cells and

establishment in an in vitro medium (sometimes in soft agar); (2) incubation of the cells with

various drugs; (3) assessment of cell survival; and (4) interpretation of the result.

Background

A variety of chemoresistance and chemosensitivity assays have been clinically evaluated in

human trials. All assays use characteristics of cell physiology to distinguish between viable and

nonviable cells to quantify cell kill following exposure to a drug of interest. With few exceptions,

drug doses used in the assays vary highly depending on tumor type and drug class, but all

assays require drug exposures ranging from several-fold below physiologic relevance to several-

fold above physiologic relevance. Although a variety of assays examine chemoresistance or

chemosensitivity, only a few are commercially available. Available assays are outlined below.

Methods Using Differential Staining/Dye Exclusion

Differential Staining Cytotoxicity Assay

The Differential Staining Cytotoxicity assay relies on dye exclusion of live cells after mechanical

disaggregation of cells from surgical or biopsy specimens by centrifugation.1 Cells are then

established in culture and treated with the drugs of interest at 3 dose levels: the middle

(relevant) dose, which could be achieved in therapy; a 10-fold lower dose than the

physiologically relevant dose; and a 10-fold higher dose. Exposure time ranges from four to six

days; then cells are re-stained with fast green dye and counterstained with hematoxylin and

eosin. The fast green dye is taken up by dead cells, and hematoxylin and eosin differentiates

tumor cells from normal cells. The intact cell membrane of a live cell precludes staining with the

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green dye. Drug sensitivity is measured by the ratio of the number of live cells in the treated

samples to the number of live cells in the untreated controls.

EVA/PCD Assay

The EVA/PCD assay (Rational Therapeutics) relies on ex vivo analysis of programmed cell death,

as measured by differential staining of cells after apoptotic and nonapoptotic cell death markers

in tumor samples exposed to chemotherapeutic agents. Tumor specimens obtained through

biopsy or surgical resection are disaggregated using DNase and collagenase IV to yield tumor

clusters of the desired size (50-100 cell spheroids). Because these cells are not proliferated, these

microaggregates are believed to approximate the human tumor microenvironment more closely.

These cellular aggregates are treated with the dilutions of the chemotherapeutic drugs of

interest and incubated for three days. After drug exposure is completed, a mixture of nigrosin B

and fast green dye with glutaraldehyde-fixed avian erythrocytes is added to the cellular

suspensions.2 The samples are then agitated and cytospin-centrifuged and, after air drying,

counterstained with hematoxylin and eosin. The end point of interest for this assay is cell death,

as assessed by observing the number of cells differentially stained due to changes in cellular

membrane integrity.3

Fluorometric Microculture Cytotoxicity Assay

The fluorometric microculture cytotoxicity assay is another cell viability assay that relies on the

measurement of fluorescence generated from cellular hydrolysis of fluorescein diacetate to

fluorescein in viable cells.4 Cells from tumor specimens are incubated with cytotoxic drugs; drug

resistance is associated with higher levels of fluorescence.

Methods Using Radioactive Precursors by Macromolecules in Viable Cells

Tritiated Thymine

Tritiated thymine incorporation measures uptake of tritiated thymidine by DNA of viable cells.

Using proteases and DNase to disaggregate the tissue, samples are seeded into single cell

suspension cultures on soft agar. They are then treated with the drug(s) of interest for four days.

After three days, tritiated thymidine is added. After 24 hours of additional incubation, cells are

lysed, and radioactivity is quantified and compared with a blank control consisting of cells that

were treated with sodium azide. Only cells that are viable and proliferating will take up the

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radioactive thymidine. Therefore, there is an inverse relationship between the update of

radioactivity and sensitivity of the cells to the agent(s) of interest.5

Extreme Drug Resistance Assay

The Oncotech Extreme Drug Resistance EDR® assay (Exiqon Diagnostics; no longer

commercially available) is methodologically similar to the thymidine incorporation assay, using

metabolic incorporation of tritiated thymidine to measure cell viability; however, single cell

suspensions are not required, so the assay is simpler to perform.6 Tritiated thymidine is added to

the cultures of tumor cells, and uptake is quantified after various incubation times. Only live

(resistant) cells will incorporate the compound. Therefore, the level of tritiated thymidine

incorporation is directly related to chemoresistance. The interpretation of the results is unique in

that resistance to the drugs is evaluated, as opposed to evaluation of responsiveness. Tumors

are considered to be highly resistant when thymidine incorporation is at least 1 standard

deviation above reference samples.

Methods Quantifying Cell Viability Using Colorimetric Assay

Histoculture Drug Resistance Assay

The Histoculture Drug Resistance Assay HDRA® (AntiCancer) evaluates cell growth after

chemotherapy treatment based on a colorimetric assay that relies on mitochondrial

dehydrogenases in living cells.7 Drug sensitivity is evaluated by quantification of cell growth in

the 3-dimensional collagen matrix. There is an inverse relation between the drug sensitivity of

the tumor and cell growth. Concentrations of drug and incubation times are not standardized

and vary depending on drug combination and tumor type.

Methods Using Chemoluminescent Precursors by Macromolecules in

Viable Cells

Adenosine Triphosphate Bioluminescence Assay

The adenosine triphosphate (ATP) bioluminescence assay relies on the measurement of ATP to

quantify the number of viable cells in a culture. Single cells or small aggregates are cultured and

then exposed to drugs. Following incubation with drug, the cells are lysed, and the cytoplasmic

components are solubilized under conditions that will not allow enzymatic metabolism of ATP.

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Luciferin and firefly luciferase are added to the cell lysis product. This catalyzes the conversion of

ATP to adenosine di- and monophosphate, and light is emitted proportionally to metabolic

activity. This is quantified with a luminometer. From the measurement of light, the number of

cells can be calculated. A decrease in ATP indicates drug sensitivity, whereas no loss of ATP

suggests the tumor is resistant to the agent of interest.

ChemoFX Assay

The ChemoFX (Helomics, previously called Precision Therapeutics) assay also relies on

quantifying ATP-based on chemoluminescence.8,9 Cells must be grown in a monolayer rather

than in a 3-dimensional matrix.

Summary of Evidence

For individuals who have cancer who are initiating chemotherapy who receive chemoresistance

assays, the evidence includes correlational observational studies. Relevant outcomes are overall

survival, disease-specific survival, test accuracy and validity, and quality of life. Some

retrospective and prospective correlational studies have suggested that chemoresistance assays

may be associated with chemotherapy response. However, prospective studies have not

consistently demonstrated that chemoresistance assay results are associated with survival.

Furthermore, no studies were identified that compared outcomes for patients managed using

assay-directed therapy with those managed using physician-directed therapy. Large,

randomized, prospective clinical studies comparing overall survival are needed. The evidence is

insufficient to determine the effects of the technology on health outcomes.

For individuals who have cancer who are initiating chemotherapy who receive chemosensitivity

assays, the evidence includes an RCT, non-randomized studies, and correlational observational

studies. The relevant outcomes are overall survival, disease-specific survival, test accuracy and

validity, and quality of life. The most direct evidence on the effectiveness of chemosensitivity

assays in the management of patients with cancer comes from several studies comparing

outcomes for patients managed using a chemosensitivity assay with those managed with

standard care, including a RCT. Although some improvements in tumor response were noted in

the randomized trial, there were no differences in survival outcomes. One small nonrandomized

study reported improved overall survival in patients receiving chemosensitivity-guided therapy

compared with patients receiving standard chemotherapy. A number of retrospective and

prospective studies of several different chemosensitivity assays have suggested that patients

whose tumors have higher chemosensitivity have better outcomes. Currently, additional studies

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to determine whether the clinical use of in vitro chemosensitivity testing leads to improvements

in overall survival are needed. The evidence is insufficient to determine the effects of the

technology on health outcomes.

Ongoing and Unpublished Clinical Trials

Some ongoing trials that might influence this policy are listed in Table 1.

Table 1. Summary of Key Trials

NCT No. Trial Name Planned

Enrollment

Completion

Date

Ongoing

NCT02580253 Adjuvant Chemotherapy Based on the Adenosine

Triphosphate Tumor Chemosensitivity Assay for

Hepatocellular Carcinoma After Liver Transplantation

300 Dec 2018

NCT03133273a Study of the Therapeutic Response and survival of Patients

with Metastatic Colorectal Cancer (Stage IV) and Treated

According to the Guidelines of a Chemosensitivity Test,

Oncogramme®

230 Jul 2020

NCT: national clinical trial.

a Denotes industry-sponsored or cosponsored trial.

Practice Guidelines and Position Statements

National Comprehensive Cancer Network

Epithelial Ovarian Cancer/ Fallopian Tube Cancer/ Primary Peritoneal Cancer

Current National Comprehensive Cancer Network (NCCN; v.1.2019) guidelines for the treatment

of epithelial ovarian cancer, fallopian tube cancer, and primary peritoneal cancer state that

“Chemosensitivity/resistance and/or other biomarker assays are being used in some NCCN

Member Institutions for decisions related to future chemotherapy in situations where there are

multiple equivalent chemotherapy options available. The current level of evidence is not

sufficient to supplant standard-of-care chemotherapy. (category 3)”54

https://www.clinicaltrials.gov/ct2/show/NCT02580253?term=NCT02580253&rank=1https://www.clinicaltrials.gov/ct2/show/NCT03133273?term=NCT03133273&rank=1

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Gastric Cancer

The NCCN (v.2.2019) guidelines for the treatment of gastric cancer55 do not discuss the use of

chemoresistance or chemosensitivity assays as part of cancer management.56

Breast Cancer

The NCCN (v.1.2019) guidelines for the treatment of breast cancer do not discuss the use of

chemoresistance or chemosensitivity assays as part of cancer management.57

Melanoma

The NCCN (v.2.2019) guidelines for the treatment of cutaneous melanoma do not discuss the

use of chemoresistance or chemosensitivity assays as part of cancer management.58

Non-Small Cell Lung Cancer

The NCCN (v.4.2019) guidelines for the treatment of non-small cell lung cancer do not discuss

the use of chemoresistance or chemosensitivity assays as part of cancer management.59

Uterine Neoplasms

The NCCN (v.3.2019) guidelines for the treatment of uterine neoplasms do not discuss the use

of chemoresistance or chemosensitivity assays as part of cancer management.60

American Society of Clinical Oncology

The updated American Society of Clinical Oncology (2011) clinical guidelines on the use of

chemotherapy sensitivity and resistance assays did not recommend use of chemotherapy

sensitivity and resistance assays unless in a clinical trial setting.61

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Medicare National Coverage

There is no national coverage determination.

Regulatory Status

Clinical laboratories may develop and validate tests in-house and market them as a laboratory

service; laboratory-developed tests must meet the general regulatory standards of the Clinical

Laboratory Improvement Amendments. Chemoresistance and chemosensitivity assays discussed

in this policy are available under the auspices of Clinical Laboratory Improvement Amendments.

Laboratories that offer laboratory-developed tests must be licensed by Clinical Laboratory

Improvement Amendments for high-complexity testing. To date, the U.S. Food and Drug

Administration has chosen not to require any regulatory review of this test.

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54. National Comprehensive Cancer Network. NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines): Ovarian Cancer

Including Fallopian Tube Cancer and Primary Peritoneal Cancer. Ver. 1.2019. Published March 8, 2019.

https://www.nccn.org/professionals/physician_gls/pdf/ovarian.pdf. Accessed September 2019.

55. National Comprehensive Cancer Network (NCCN). NCCN Clinical Practice Guidelines in Oncology: Gastric Cancer. Version

2.2018. https://www.nccn.org/professionals/physician_gls/pdf/gastric.pdf. Accessed September 2019.

56. National Comprehensive Cancer Network. NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines): Gastric Cancer.

Ver. 2.2019. Published June 3, 2019. https://www.nccn.org/professionals/physician_gls/pdf/gastric.pdf. Accessed

September 2019.

57. National Comprehensive Cancer Network. NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines): Breast Cancer. Ver.

1.2019. Published March 14, 2019. https://www.nccn.org/professionals/physician_gls/pdf/breast.pdf. Accessed September

2019.

58. National Comprehensive Cancer Network. NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines): Cutaneous

Melanoma. Ver. 2.2019. Published March 12, 2019.

https://www.nccn.org/professionals/physician_gls/pdf/cutaneous_melanoma.pdf. Accessed September 2019.

59. National Comprehensive Cancer Network. NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines): Non-Small Cell

Lung Cancer. Ver. 4.2019. Published April 29, 2019. https://www.nccn.org/professionals/physician_gls/pdf/nscl.pdf.

Accessed September 2019.

60. National Comprehensive Cancer Network. NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines): Uterine

Neoplasms. Ver. 3.2019. Published February 11, 2019. https://www.nccn.org/professionals/physician_gls/pdf/uterine.pdf.

Accessed September 2019.

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of chemotherapy sensitivity and resistance assays. J Clin Oncol. Aug 20 2011;29(24):3328- 3330. PMID 21788567.

History

Date Comments 05/05/97 Add to Medicine Section - New Policy.

https://www.nccn.org/professionals/physician_gls/pdf/ovarian.pdfhttps://www.nccn.org/professionals/physician_gls/pdf/gastric.pdfhttps://www.nccn.org/professionals/physician_gls/pdf/gastric.pdfhttps://www.nccn.org/professionals/physician_gls/pdf/breast.pdfhttps://www.nccn.org/professionals/physician_gls/pdf/nscl.pdfhttps://www.nccn.org/professionals/physician_gls/pdf/uterine.pdf

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Date Comments 08/17/99 Replace Policy - Updated; policy unchanged.

09/21/00 Replace Policy - Policy updated with reference to TEC Assessment; policy statement

unchanged.

03/11/03 Replace Policy - Policy reviewed; policy statement unchanged; 2002 updates and

references added.

01/01/04 Replace Policy - CPT code updates only.

05/11/04 Replace Policy - Policy reviewed; policy statement unchanged, updated references

provided.

01/11/05 Replace Policy - Policy reviewed; policy statement unchanged; references added.

11/11/05 Replace Policy - Policy reviewed; policy statement unchanged; references updated.

06/23/06 Update Scope and Disclaimer - No other changes.

10/10/06 Replace Policy - Policy reviewed with reference added; policy statement unchanged.

12/11/07 Delete Policy - No longer reviewed; policy deleted.

12/14/10 Re-instate Policy - The policy has been reinstated to facilitate current request and

support non-payment; additional code added 89240.

07/12/11 Replace Policy - Policy updated with literature search. References 18, 30, 33, and 36

added. No change to policy statements. ICD-10 codes added to policy.

05/22/12 Replace policy. Policy updated with literature search. No new references added. Policy

statements unchanged.

09/17/12 Update Coding Section – ICD-10 codes are now effective 10/01/2014.

07/26/13 Replace policy. Policy updated with literature search through March 2013. References

2, 3, 21, and 40 added. No change to policy statements.

06/19/14 Annual Review. Background and rationale sections reorganized. Policy updated with

literature review through March 6, 2014. References 6-8, 40-42, 45, 47, 48 added;

others renumbered/removed. Policy statements unchanged.

07/14/15 Archive Policy. This is old technology which has been replaced by genetic testing.

There are few requests.

11/10/15 Re-instituting this policy due to more utilization and high cost of the test. Policy

updated with literature review through March 12, 2015. References 4, 41-42, and 50

added. “ChemoFx” and “CorrectChemo” added to the list of investigational

chemosensitivity assays; policy statements otherwise unchanged.

01/19/16 Coding update. New CPT codes 81535 and 81536, effective 01/01/16, added to policy.

10/01/16 Annual Review, approved September 13, 2016. Policy updated with literature search

through June 2016; reference added. Policy statements unchanged.

11/01/17 Annual Review, approved October 19, 2017. Policy updated with literature search

Page | 14 of 14 ∞

Date Comments through June 20, 2017; reference 35 and 49 added. Policy statements unchanged.

10/01/18 Annual Review, approved September 20, 2018. Policy updated with literature search

through May 2018; reference 9 added. CorrectChemo assay removed from the second

policy statement; intent of statements unchanged. Removed CPT code 89240.

10/01/19 Annual Review, approved September 5, 2019. Policy updated with literature search

through May 2019; no references added. Policy statements unchanged.

01/01/20 Coding updated, added CPT code 0564T (new code effective 1/1/20).

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.

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.

Discrimination is Against the Law

Premera Blue Cross complies with applicable Federal civil rights laws and does not discriminate on the basis of race, color, national origin, age, disability, or sex. Premera does not exclude people or treat them differently because of race, color, national origin, age, disability or sex.

Premera: • Provides free aids and services to people with disabilities to communicate

effectively with us, such as: • Qualified sign language interpreters • Written information in other formats (large print, audio, accessible

electronic formats, other formats) • Provides free language services to people whose primary language is not

English, such as: • Qualified interpreters• Information written in other languages

If you need these services, contact the Civil Rights Coordinator.

If you believe that Premera has failed to provide these services or discriminated in another way on the basis of race, color, national origin, age, disability, or sex, you can file a grievance with: Civil Rights Coordinator - Complaints and Appeals PO Box 91102, Seattle, WA 98111 Toll free 855-332-4535, Fax 425-918-5592, TTY 800-842-5357 Email AppealsDepartmentInquiries@Premera.com

You can file a grievance in person or by mail, fax, or email. If you need help filing a grievance, the Civil Rights Coordinator is available to help you.

You can also file a civil rights complaint with the U.S. Department of Health and Human Services, Office for Civil Rights, electronically through the Office for Civil Rights Complaint Portal, available at https://ocrportal.hhs.gov/ocr/portal/lobby.jsf, or by mail or phone at: U.S. Department of Health and Human Services 200 Independence Avenue SW, Room 509F, HHH Building Washington, D.C. 20201, 1-800-368-1019, 800-537-7697 (TDD) Complaint forms are available at http://www.hhs.gov/ocr/office/file/index.html.

Getting Help in Other Languages

This Notice has Important Information. This notice may have important information about your application or coverage through Premera Blue Cross. There may be key dates in this notice. You may need to take action by certain deadlines to keep your health coverage or help with costs. You have the right to get this information and help in your language at no cost. Call 800-722-1471 (TTY: 800-842-5357).

አማሪኛ (Amharic): ይህ ማስታወቂያ አስፈላጊ መረጃ ይዟል። ይህ ማስታወቂያ ስለ ማመልከቻዎ ወይም የ Premera Blue Cross ሽፋን አስፈላጊ መረጃ ሊኖረው ይችላል። በዚህ ማስታወቂያ ውስጥ ቁልፍ ቀኖች ሊኖሩ ይችላሉ። የጤናን ሽፋንዎን ለመጠበቅና በአከፋፈል እርዳታ ለማግኘት በተውሰኑ የጊዜ ገደቦች እርምጃ መውሰድ ይገባዎት ይሆናል። ይህን መረጃ እንዲያገኙ እና ያለምንም ክፍያ በቋንቋዎ እርዳታ እንዲያገኙ መብት አለዎት።በስልክ ቁጥር 800-722-1471 (TTY: 800-842-5357) ይደውሉ።

( ةالعربي :(. امةھ ماتولعم اإلشعار ھذا يحوي

خالل من ھاعلي صولحلا تريد لتيا التغطيةلل أو ةصحيلاكطيتتغ لىع اظلحفل نةعيم يخراوت في إجراء خاذتال تحتاج وقد .اإلشعار ھذا في

تكلفة أية بدتك دون بلغتك مساعدةوال تاوملالمع ھذه على ولحصال لك يحق .800-722-1471 (TTY: 800-842-5357)

أو طلبك وصخصب مةمھ ماتوعلم عارشإلا ھذا ويحي قدةمھم يخراوت ھناك تكون قد .Premera Blue Cross

اعدةمس تصلايفكالتال دفع فيبـ

.

Arabic

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Italian

中文 (Chinese):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

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

語得到本訊息和幫助。請撥電話 800-722-1471 (TTY: 800-842-5357)。

037338 (07-2016)

https://www.hhs.gov/ocr/office/file/index.htmlhttps://ocrportal.hhs.gov/ocr/portal/lobby.jsfmailto:AppealsDepartmentInquiries@Premera.com

日本語 (Japanese):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 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

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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

トが無料で提供されます。800-722-1471 (TTY: 800-842-5357)までお電話ください。

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ລາວ (Lao): ແຈ້ງການນີ້ ນສໍ າຄັນ. ແຈ້ງການນີ້ອາດຈະມີ ນສໍ າຄັນກ່ຽວກັບຄໍ າຮ້ອງສະ ກ ຫຼື ຄວາມຄຸ້ມຄອງປະກັນໄພຂອງທ່ານຜ່ານ Premera Blue Cross. ອາດຈະມີ ນທີ າຄັນໃນແຈ້ງການນີ້. ທ່ານອາດຈະຈໍ າເປັ ນຕ້ອງດໍ າເນີ ນການຕາມກໍ ານົດ ເວລາສະເພາະເພື່ອຮັກສາຄວາມຄຸ້ມຄອງປະກັນສຸຂະພາບ ຫຼື ຄວາມຊ່ວຍເຫຼື ອເລື່ອງ າໃຊ້ າຍຂອງທ່ານໄວ້ . ທ່ານມີ ດໄດ້ ບຂໍ້ ນນີ້ ແລະ ຄວາມຊ່ວຍເຫຼື ອເປັ ນພາສາ ຂອງທ່ານໂດຍບ່ໍ ເສຍຄ່າ. ໃຫ້ໂທຫາ 800-722-1471 (TTY: 800-842-5357).

ູຂໍ້

່

ສໍ ັ

ຈ

ໝ

ສິ

ັ

່

ວ

ຄ

ມ

ມູຮັ

ູມີ ມຂໍ້

ភាសាែខមរ ( ): ឹ

រងរបស់

Premera Blue Cross ។ របែហលជាមាន កាលបរ ិ ឆ ំខានេនៅកងេសចក

េសចកតជី ូ

ជាមានព័ ៌ ៉ ងសំ ់អពី ់ ៉ ប់

នដំ ងេនះមានព័ ី

តមានយា ខាន ំ ទរមងែបបបទ ឬការរា

ណ ត៌មានយ៉ា ំ ់ តងសខាន។ េសចក

េចទស ់ ន ុ ត

ណងេនះ។ អ វការបេញញសមតភាព ដលកណតៃថ ចបាស

កតាមរយៈ

ដំ ឹ នករបែហលជារតូ ច ថ ់ ំ ់ ងជាក់ ់

នដ

ន

ី ន

ូ

អ

ូ

ជ

ជ

ំណឹងេនះរបែហល

នានា េដើ ីនងរកសាទុ ៉ បរងស់ ុ ់ ក ឬរបាក់ ំ

អ

មប ឹ កការធានារា ខភាពរបស ជ

ធនកមានសិ ទទលព័ មានេនះ និ ំ យេនៅកុងភាសារបសទិ ួ ត៌ ងជ ននួ

ន

់ កេដាយម

អ

នអ

យេចញៃថល។ ួ

នអស

ន

ិ

លុ ើ ូ ូយេឡយ។ សមទ ទ រស័ព 800-722-1471 (TTY: 800-842-5357)។

Khmer

ਕਵਰਜ ਅਤ ਅਰਜੀ ਬਾਰ ਮਹ ਤਵਪਰਨ ਜਾਣਕਾਰੀ ਹ ਸਕਦੀ ਹ . ਇਸ ਨ ਿਜਸ ਜਵਚ ਖਾਸ

ਤਾਰੀਖਾ ਹ ਸਕਦੀਆ ਹਨ. ਜੇਕਰ ਤਸੀ ਜਸਹਤ ਕਵਰਜ ਿਰਖਣੀ ਹਵ ਜਾ ਓਸ ਦੀ ਲਾਗਤ ਜਿਵਚ ਮਦਦ ਦ ੇਇਛ ੁਕ ਹ ਤਾਂ ਤਹਾਨ ਅ ਤਮ ਤਾਰੀਖ਼ ਤ ਪਿਹਲਾਂ ਕੁ ਝ ਖਾਸ ਕਦਮ ਚ ਕਣ ਦੀ ਲੜ ਹ ਸਕਦੀ ਹ ,ਤਹੁਾਨ ਮਫ਼ਤ ਿਵਚ ਤ ਆਪਣੀ ਭਾਸ਼ਾ ਿਵ ਚ ਜਾਣਕਾਰੀ ਅਤ ਮਦਦ ਪਾਪਤ ਕਰਨ ਦਾ ਅਿਧਕਾਰ ਹ ,ਕਾਲ 800-722-1471 (TTY: 800-842-5357).

ਪ ਜਾਬੀ (Punjabi): ਇਸ ਨ ਿਟਸ ਿਵਚ ਖਾਸ ਜਾਣਕਾਰੀ ਹ. ਇਸ ਨ ਿਟਸ ਿਵਚ Premera Blue Cross ਵਲ ਤੁਹਾਡੀ

ੰ

ੰ

ੇ ੇ ੇ ੱ ੂ ੋ ੈ ੋੋ ਂ ੁ ੇ ੱ ੋ ੇ ੱੱ ੁ ੱ ੂੁ ੱ ੇ ੱ ੇ ੍ਰ ੈ

ੋ ੰ ੂ ੱ ੁ ੋ ੋ ੈ ੰ

ੋ ੈ ੋ

(Farsi): فارسی فرم بارهدر ھمم اطالعات حاوی است ممکن يهمالعا اين. ميباشد ھمم اطالعات یوحا يهمالعا اين

در ھمم ھای خيتار به باشد.پ رایبستاکنممماش زينهھ اختدپر در مککيا تان بيمهوشش حقظ

Premera Blue Cross طريق از ماش مهبيوشش يا و تقاضا ای پ. يدماين جهتو يهمالعا اين

حق شما. يدشاب داشته اجتياح صیاخ کارھای امانج برای صیمشخ ایھ خيتار به تان، انیمدر ھای کسب برای .نماييد دريافت گانيرا ورط به ودخ زبان به را کمک و اطالعات اين که داريد را اين

استم ) 5357-842-800 مارهباش ماست TTY انکاربر(800-722-1471 مارهش با اطالعات .اييدنم برقرار

้

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zawierać ważne informacje odnośnie Państwa wniosku lub zakresu świadczeń poprzez Premera Blue Cross. Prosimy zwrócic uwagę na kluczowe daty, które mogą być zawarte w tym ogłoszeniu aby nie przekroczyć terminów w przypadku utrzymania polisy ubezpieczeniowej lub pomocy związanej z kosztami. Macie Państwo prawo do bezpłatnej informacji we własnym języku. Zadzwońcie pod 800-722-1471 (TTY: 800-842-5357).

Português (Portuguese): Este aviso contém informações importantes. Este aviso poderá conter informações importantes a respeito de sua aplicação ou cobertura por meio do Premera Blue Cross. Poderão existir datas importantes neste aviso. Talvez seja necessário que você tome providências dentro de determinados prazos para manter sua cobertura de saúde ou ajuda de custos. Você tem o direito de obter e sta informação e ajuda em seu idioma e sem custos. Ligue para 800-722-1471 (TTY: 800-842-5357).

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Pусский (Russian): Настоящее уведомление содержит важную информацию. Это уведомление может содержать важную информацию о вашем заявлении или страховом покрытии через Premera Blue Cross. В настоящем уведомлении могут быть указаны ключевые даты. Вам, возможно, потребуется принять меры к определенным предельным срокам для сохранения страхового покрытия или помощи с расходами. Вы имеете право на бесплатное получение этой информации и помощь на вашем языке. Звоните по телефону 800-722-1471 (TTY: 800-842-5357).

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Español ( ): Este Aviso contiene información importante. Es posible que este aviso contenga información importante acerca de su solicitud o cobertura a través de Premera Blue Cross. Es posible que haya fechas clave en este

tiene derecho a recibir esta información y ayuda en su idioma sin costo

aviso. Es posible que deba tomar alguna medida antes de determinadas fechas para mantener su cobertura médica o ayuda con los costos. Usted

alguno. Llame al 800-722-1471 (TTY: 800-842-5357).

Spanish

Tagalog (Tagalog): Ang Paunawa na ito ay naglalaman ng mahalagang impormasyon. Ang paunawa na ito ay maaaring naglalaman ng mahalagang impormasyon tungkol sa iyong aplikasyon o pagsakop sa pamamagitan ng Premera Blue Cross. Maaaring may mga mahalagang petsa dito sa paunawa. Maaring mangailangan ka na magsagawa ng hakbang sa ilang mga itinakdang panahon upang mapanatili ang iyong pagsakop sa kalusugan o tulong na walang gastos. May karapatan ka na makakuha ng ganitong impormasyon at tulong sa iyong wika ng walang gastos. Tumawag sa 800-722-1471 (TTY: 800-842-5357).

ไทย (Thai): ประกาศนมขอมลสาคญ ประกาศนอาจมขอมลทสาคญเกยวกบการการสมครหรอขอบเขตประกน สขภาพของคณผาน Premera Blue Cross และอาจมกาหนดการในประกาศน คณอาจจะตอง ดาเนนการภายในกาหนดระยะเวลาทแนนอนเพอจะรกษาการประกนสขภาพของคณหรอการชวยเหลอท มคาใชจาย คณมสทธทจะไดรบขอมลและความชวยเหลอนในภาษาของคณโดยไม่มคาใชจาย โทร 800-722-1471 (TTY: 800-842-5357)

้ี ี ้ ู ํ ั ้ี ี ้ ู ่ี ํ ั ่ี ั ั ื ัุ ุ ่ ี ํ ี ุ ้ํ ิ ํ ่ี ่ ่ื ั ั ุ ุ ื ่ ื ่ีี ่ ้ ่ ุ ี ิ ิ ่ี ้ ั ้ ู ่ ื ้ี ุ ี ่ ้ ่

Український (Ukrainian): Це повідомлення містить важливу інформацію. Це повідомлення може містити важливу інформацію про Ваше звернення щодо страхувального покриття через Premera Blue Cross. Зверніть увагу на ключові дати, які можуть бути вказані у цьому повідомленні. Існує імовірність того, що Вам треба буде здійснити певні кроки у конкретні кінцеві строки для того, щоб зберегти Ваше медичне страхування або отримати фінансову допомогу. У Вас є право на отримання цієї інформації та допомоги безкоштовно на Вашій рідній мові. Дзвоніть за номером телефону 800-722-1471 (TTY: 800-842-5357).

Tiếng Việt (Vietnamese): Thông báo này cung cấp thông tin quan trọng. Thông báo này có thông tin quan trọng về đơn xin tham gia hoặc hợp đồng bảo hiểm của quý vị qua chương trình Premera Blue Cross. Xin xem ngày quan trọng trong thông báo này. Quý vị có thể phải thực hiện theo thông báo đúng trong thời hạn 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).