Notification



Notification Issue Date:



Medicare Advantage Policy

Title:Islet Cell Transplantation
Policy #:MA11.007a

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


The Company makes decisions on coverage based on the Centers for Medicare and Medicaid Services (CMS) regulations and guidance, benefit plan documents and contracts, and the member’s medical history and condition. If CMS does not have a position addressing a service, the Company makes decisions based on Company Policy Bulletins. Benefits may vary based on contract, and individual member benefits must be verified. The Company determines medical necessity only if the benefit exists and no contract exclusions are applicable. Although the Medicare Advantage Policy Bulletin is consistent with Medicare’s regulations and guidance, the Company’s payment methodology may differ from Medicare.

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


This Policy Bulletin document describes the status of CMS coverage, medical terminology, and/or benefit plan documents and contracts at the time the document was developed. This Policy Bulletin will be reviewed regularly and be updated as Medicare changes their regulations and guidance, scientific and medical literature becomes available, and/or the benefit plan documents and/or contracts are changed.



Policy

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

MEDICALLY NECESSARY

Autologous islet cell transplantation is considered medically necessary and, therefore, covered as an adjunct to a total or near-total pancreatectomy in individuals with chronic pancreatitis.

EXPERIMENTAL/INVESTIGATIONAL

Autologous islet cell transplantation is considered experimental/investigational and, therefore, not covered for all other indications because the safety and/or effectiveness of this service cannot be established by review of the available published peer-reviewed literature.

Allogeneic islet cell transplantation is considered experimental/investigational and, therefore, not covered for all indications because the safety and/or effectiveness of this service cannot be established by review of the available published peer-reviewed literature.

REQUIRED DOCUMENTATION

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

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

This policy is consistent with Medicare's coverage determination. The Company's payment methodology may differ from Medicare.

BENEFIT APPLICATION

Subject to the terms and conditions of the applicable Evidence of Coverage, autologous islet cell transplantation as an adjunct to a total or near-total pancreatectomy in individuals with chronic pancreatitis is covered under the medical benefits of the Company’s Medicare Advantage products when the medical necessity criteria listed in this medical policy are met.

Subject to the terms and conditions of the applicable Evidence of Coverage, allogeneic islet cell transplantation is not eligible for payment under the medical benefits of the Company’s Medicare Advantage products because the service is considered experimental/investigational and, therefore, not covered. Services that are experimental/investigational are excluded for the Company's Medicare Advantage products. Therefore, they are not eligible for reimbursement consideration.

Pancreatic islet cell transplantation for individuals with type 1 diabetes who participate in a clinical trial sponsored by the National Institutes of Health (NIH) may be covered and reimbursed by the local Medicare Administrative Contractor (MAC).

Description

The pancreas is an organ located behind the lower part of the stomach. One of the major functions of the pancreas is the production of two hormones: insulin and glucagon. The production of these hormones takes place in endocrine cell clusters located on the pancreas called the islets of Langerhans. The islets of Langerhans make up approximately 1 percent to 2 percent of the total pancreas.

There are about one million islets in a healthy adult. Most islet cells are concentrated towards the tail end of the pancreas. Islets are mostly composed of two types of cells: alpha cells, which produce glucagon, a hormone that raises the level of glucose (sugar) in the blood, and beta cells, which produce insulin, a hormone that reduces the level of glucose in the blood by helping the body use glucose for energy.

Islet cell transplant tissue comes either from the patient (autologous transplant) or from a cadaveric donor (allogeneic transplant). Islet cell transplantation may benefit an individual who is without a functioning pancreas. Currently, only individuals with either chronic pancreatitis or type 1 diabetes mellitus have been the subject of clinical investigations.

CHRONIC PANCREATITIS

Chronic pancreatitis is a condition that destroys the pancreas and other tissues. Symptoms include severe abdominal pain, weight loss, fever, nausea, and vomiting. Individuals with chronic pancreatitis can experience intractable pain that can only be relieved with a total or near-total pancreatectomy. After a pancreatectomy, the individual will benefit from pain relief, but will become an insulin-dependent diabetic (surgically induced diabetes) due to the loss of insulin-producing islet cells.

Autologous islet transplantation is a technique to prevent the serious morbidity of surgically induced diabetes due to the removal of the individual's pancreas. Although the pancreatotomy and transplant can be performed on two different days, the transplant is generally performed during the pancreatectomy procedure. During the pancreatectomy, a suspension is created by mixing plasma and the isolated islet cells collected from the individual's own resected pancreatic specimen. This suspension is then injected into the portal vein of the liver, where the cells function as a free graft. There is no risk of rejection because, unlike allogeneic organ/tissue transplants, the individual's own islet cells are used in the procedure.

Although the published literature regarding autologous islet cell transplantation is limited, this procedure has been shown to significantly decrease the occurrence of surgically induced diabetes after a total or near-total pancreatectomy. Additionally, autologous islet cell transplantation has not been associated with serious morbidity.

Conversely, the level of evidence in the literature is insufficient to demonstrate the efficacy of autologous islet cell transplantation performed for any other indication.

TYPE 1 DIABETES MELLITUS

Type 1 diabetes mellitus results from cellular autoimmune destruction of the beta cells in the islets of Langerhans in the pancreas. Islet cell autoantibodies (ICAs) are theorized to cause the individual to reject his own islet cells, leading to an absolute insulin deficiency. ICAs have been detected in many type I diabetic individuals.

Allogeneic islet cell transplantation has been proposed as a treatment for type 1 diabetes in order to restore normoglycemia. By restoring normoglycemia, it is hoped that an islet cell transplant will reduce or eliminate the long-term complications of diabetes, such as retinopathy, neuropathy, nephropathy, and cardiovascular disease. Islet cell transplantation is a potential alternative to whole-organ pancreas transplantation.

Individuals with type 1 diabetes do not have viable beta cells for autologous transplantation and, therefore, cannot receive an autologous transplant. Allogeneic (donor) islet cell transplantation has had little success clinically. In addition to the immune system rejecting foreign tissue, the presence of ICAs is another confounding factor because ICAs add an additional rejection complication for allogeneic islet cells in individuals with type 1 diabetes mellitus.

While the techniques for allogeneic islet cell transplantation are evolving, the impact on net health outcomes is uncertain. Longer follow-up is needed to evaluate the long-term safety of allogeneic islet cell transplantation and its impact on complications of diabetes mellitus.

Allogeneic islet cells are subject to regulation by the US Food and Drug Administration (FDA), which classifies allogeneic islet cell transplantation as somatic cell therapy; therefore, allogeneic islet cells require premarket approval. Additionally, allogeneic islet transplantation must be conducted under FDA investigational new drug (IND) regulations.
References

Aguayo-Mazzucato C, Bonner-Weir S. Stem cell therapy for type 1 diabetes mellitus. Nat Rev Endocrinol. 2010;6(3):139-48.

Alejandro R, Barton FB, Hering BJ, et al. 2008 Update from the Collaborative Islet Transplant Registry. Transplantation. 2008; 86(12):1783-8.

Badet L, Benhamou PY, Wojtusciszyn A, et al; GRAGIL Group. Expectations and strategies regarding islet transplantation: metabolic data from the GRAGIL 2 trial. Transplantation. 2007;84(1):89-96.

Barton FB, Rickels MR, Alejandro R, et al. Improvement in outcomes of clinical islet transplantation: 1999-2010. Diabetes Care. 2012; 35(7):1436-45.

Bramis K, Gordon-Weeks AN, Friend PJ, et al. Systematic review of total pancreatectomy and islet autotransplantation for chronic pancreatitis. Br J Surg. 2012;99(6):761-6.

Caiazzo R, Vantyghem MC, Raverdi V, et al. Impact of Procedure-Related Complications on Long-Term Islet Transplantation Outcome. Transplantation. 2015;99(5):979-84.

Centers for Medicare and Medicaid. National Coverage Determination (NCD) for ISLET CELL Transplantation in the Context of a Clinical Trial (260.3.1). [CMS Web site]. 2004. Available at: https://www.cms.gov/medicare-coverage-database/details/ncd-details.aspx?NCDId=286&ncdver=1&CoverageSelection=Both&ArticleType=All&PolicyType=Final&s=All&KeyWord=islet+cell&KeyWordLookUp=Title&KeyWordSearchType=And&bc=gAAAABAAAAAA&. Accessed October 1, 2019.

Chinnakotla S, Radosevich DM, Dunn TB, et al. Long-term outcomes of total pancreatectomy and islet auto transplantation for hereditary/genetic pancreatitis. J Am Coll Surg. 2014; 218(4):530-43.

Close N, Alejandro R, Hering B, Appel M; CITR Investigators. Second annual analysis of the collaborative islet transplant registry. Transplant Proc. 2007;39(1):179-182.

Collaborative Islet Transplant Registry (CITR). CITR Annual Report. [CITR Web site]. 12/08/2016. Available at: http://www.citregistry.org/. Accessed June 15, 2018.

de Vos P, Spasojevic M, Faas MM. Treatment of diabetes with encapsulated islets. Adv Exp Med Biol. 2010;670:38-53.

Dong M, Parsaik AK, Erwin PJ, et al. Systematic review and meta-analysis: islet autotransplantation after pancreatectomy for minimizing diabetes. Clin Endocrinol (Oxf). 2011;75(6):771-9.

ECRI Institute. Indications and Contraindications for Islet Cell Transplantation for Treating Type 1 Diabetes. Plymouth Meeting (PA): ECRI Institute; May 27, 2015. (ECRI Custom Rapid Responses). Also available at: http://www.ecri.org. Accessed October 1, 2019.

Ekser B, Cooper DK. Overcoming the barriers to xenotransplantation: prospects for the future. Expert Rev Clin Immunol. 2010;6(2):219-30.

Fiorina P, Secchi A. Pancreatic islet cell transplant for treatment of diabetes. Endocrinol Metab Clin North Am. 2007; 36(4):999-1013.

Frank A, Deng S, Huang X, et al. Transplantation for type I diabetes: comparison of vascularized whole-organ pancreas with isolated pancreatic islets. Ann Surg. 2004;240(4):631-643.

Froud T, Ricordi C, Baidal DA, et al. Islet transplantation in type 1 diabetes mellitus using cultured islets and steroid-free immunosuppression: Miami experience. Am J Transplant. 2005;5(8):2037-2046.

Health Quality Ontario. Pancreas islet transplantation for patients with type 1 diabetes mellitus: a clinical evidence review. Ont Health Technol Assess Ser. 2015;15(16):1-84.

Lablanche S, Vantyghem MC, Kessler L, et al. Islet transplantation versus insulin therapy in patients with type 1 diabetes with severe hypoglycaemia or poorly controlled glycaemia after kidney transplantation (TRIMECO): a multicentre, randomised controlled trial. Lancet Diabetes Endocrinol. 2018 6(7):527-537.

National Institute for Health and Clinical Excellence (NICE). Allogenic pancreatic islet cell transplantation for type 1 diabetes mellitus [IPG257]. April 2008. Available at: http://www.nice.org.uk/Guidance/IPG257. Accessed October 1, 2019.

National Institute for Health and Clinical Excellence (NICE). Autologous pancreatic islet cell transplantation for improved glycemic control after pancreatectomy [IPG274]. September 2008. Available at: http://www.nice.org.uk/Guidance/IPG274. Accessed October 1, 2019.

O'Connell PJ, Holmes-Walker DJ, Goodman D, et al. Multicenter Australian trial of islet transplantation: improving accessibility and outcomes. Am J Transplant. 2013;13(7):1850-8.

Pavlakis M, Khwaja K. Pancreas and islet cell transplantation in diabetes. Curr Opin Endocrinol Diabetes Obes. 2007;14(2):146-150.

Piper M, Seidenfeld J, Aronson N. Islet transplantation in patients with type 1 diabetes mellitus. Evid Rep Technol Assess (Summ). 2004;(98):1-6.

Posselt AM, Szot GL, Frassetto LA, et al. Islet transplantation in type 1 diabetic patients using calcineurin inhibitor-free immunosuppressive protocols based on T-cell adhesion or costimulation blockade. Transplantation. 2010;90(12):1595-1601.

Ramesh A, Chhabra P, Brayman KL. Pancreatic islet transplantation in type 1 diabetes mellitus: an update on recent developments. Curr Diabetes Rev. 2013;9(4):294-311.

Rickels MR, Kong SM, Fuller C, et al. Improvement in insulin sensitivity after human islet transplantation for type 1 diabetes. J Clin Endocrinol Metab. 2013;98(11):E1780-1785.

Robertson RP, Lanz KJ, Sutherland DE, Kendall DM. Prevention of diabetes for up to 13 years by autoislet transplantation after pancreatectomy for chronic pancreatitis. Diabetes. 2001;50(1):47-50.

Shapiro AM, Ricordi C, Hering BJ, et al. International trial of the Edmonton protocol for islet transplantation. N Engl J Med. 2006;355(13):1318-1330.

Sutherland DE, Radosevich DM, Bellin MD, et al. Total pancreatectomy and islet autotransplantation for chronic pancreatitis. J Am Coll Surg. 2012;214(4):409-424.

Thompson DM, Meloche M, Ao Z, et al. Reduced progression of diabetic microvascular complications with islet cell transplantation compared with intensive medical therapy. Transplantation. 2011;91(3):373-378.

University Hospital Grenoble. Trial Comparing Metabolic Efficiency of Islet Graft to Intensive Insulin Therapy for Type 1 Diabetes's Treatment (TRIMECO) (NCT01148680).Available at: http://clinicaltrials.gov/ct2/show/NCT01148680. Accessed October 1, 2019.

US Food and Drug Administration (FDA). Center for Biologics Evaluation and Research. Guidance for Industry. Considerations for allogeneic pancreatic islet cell products. [FDA Web site]. September 2009. Available at: https://www.fda.gov/downloads/BiologicsBloodVaccines/GuidanceComplianceRegulatoryInformation/Guidances/CellularandGeneTherapy/UCM182441.pdf. Accessed October 1, 2019.

van der Windt DJ, Bottino R, Kumar G, et al. Clinical islet xenotransplantation: how close are we? Diabetes. 2012;61(12):3046-55.

Vantyghem MC, Raverdy V, Balavoine AS, et al. Continuous glucose monitoring after islet transplantation in type 1 diabetes: an excellent graft function (beta-score greater than 7) Is required to abrogate hyperglycemia, whereas a minimal function is necessary to suppress severe hypoglycemia (beta-score greater than 3). J Clin Endocrinol Metab. 2012; 97(11):E2078-83.

Wahoff DC, Papalois BE, Najarian JS, et al. Autologous islet transplantation to prevent diabetes after pancreatic resection. Ann Surg. 1995;222(4):562-579.

Webb MA, Illouz SC, Pollard CA, et al. Islet auto transplantation following total pancreatectomy: a long-term assessment of graft function. Pancreas. 2008; 37(3):282-7.

Wilson GC, Sutton JM, Abbott DE, et al. Long-term outcomes after total pancreatectomy and islet cell autotransplantation: is it a durable operation? Ann Surg. 2014;260(4):659-665; discussion 665-657.

Wu Q, Zhang M, Qin Y, et al. Systematic review and meta-analysis of islet autotransplantation after total pancreatectomy in chronic pancreatitis patients [Review]. Endocr J. 2015;62(3):227-234.


Coding

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

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

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

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

CPT Procedure Code Number(s)

0584T, 0585T, 0586T, 48160


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

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


ICD - 10 Procedure Code Number(s)

N/A


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

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


ICD -10 Diagnosis Code Number(s)

K86.0 Alcohol-induced chronic pancreatitis

K86.1 Other chronic pancreatitis

Z90.410 Acquired total absence of pancreas

Z90.411 Acquired partial absence of pancreas




HCPCS Level II Code Number(s)

MEDICALLY NECESSARY

G0341 Percutaneous islet cell transplant, includes portal vein catheterization and infusion

G0342 Laparoscopy for islet cell transplant, includes portal vein catheterization and infusion

G0343 Laparotomy for islet cell transplant, includes portal vein catheterization and infusion

EXPERIMENTAL/INVESTIGATIONAL

S2102 Islet cell tissue transplant from pancreas; allogeneic



Revenue Code Number(s)

N/A

Coding and Billing Requirements






Policy History

MA11.007a
01/01/2020Inclusion of a policy in a Code Update memo does not imply that a full review of
the policy was completed at this time.

This policy has been identified for the CPT code update, effective 01/01/2020.

The following CPT codes have been added to this policy: 0584T (Medically Necessary), 0585T (Medically Necessary), 0586T (Medically Necessary)

MA11.007
11/06/2019This policy has been reviewed and reissued to communicate the Company’s continuing position on Islet Cell Transplantation.
07/18/2018As of 07/18/2018, this policy has been reviewed and reissued to communicate the Company’s continuing position on islet cell transplantation.
06/21/2017This policy has been reissued in accordance with the Company's annual review process.
03/02/2016The policy has been reviewed and reissued to communicate the Company’s continuing position on Islet Cell Transplantation.
01/07/2015The policy has been reviewed and reissued to communicate the Company’s continuing position on Islet Cell Transplantation.
01/01/2015This is a new policy.




Version Effective Date: 01/01/2020
Version Issued Date: 01/02/2020
Version Reissued Date: N/A