Extracorporeal Photochemotherapy/Photopheresis
DESCRIPTION
Extracorporeal photopheresis (ECP) is a procedure in which a sizable percentage (usually 10% to 15%) of an individual's white cells are removed from the body by leukapheresis and suspended in a sample of the individual's plasma. The process begins with either the individual ingesting a photosensitizing agent or by direct addition of the photosensitizing agent to the leukapheresis product. The white cells are then exposed to ultraviolet light in a specific, relatively narrow range of wavelengths. The final process involves washing the cells to remove the photosensitizing agent and then the cells are reinfused into the individual.
ECP has been a valuable addition to the treatment of cutaneous T-cell lymphoma (CTCL) because it offers reasonable response rates (40%-60%). ECP also has very few side effects without the immunosuppression that can accompany other systemic treatments for this disease. Researchers have explored the possibility that ECP may be useful in the treatment of individuals with various other T-cell mediated diseases (e.g., graft versus host disease [GVHD], scleroderma, multiple sclerosis, and rheumatoid arthritis). GVHD can be categorized into acute, occurring within the first 100 days after infusion of allogeneic cells, or chronic disease, which develops some time after 100 days.
POLICY
Extracorporeal photochemotherapy / photopheresis for the treatment of early stage I/ II (T1and T2) and late stage III/ IV (T3 and T4) cutaneous T-cell lymphoma (CTCL) is considered medically necessary if the medical appropriateness criteria are met. (See Medical Appropriateness below.)
Extracorporeal photochemotherapy / photopheresis for the treatment of graft versus host disease (GVHD) is considered medically necessary if the medical appropriateness criteria are met. (See Medical Appropriateness below.)
Extracorporeal photochemotherapy/photopheresis for the treatment of other conditions/diseases, including, but not limited to, the following: systemic lupus erythematosus, multiple sclerosis, rheumatoid arthritis, pemphigus vulgaris, scleroderma, acute / chronic GVHD that is either previously untreated or is responding to established therapies, and acute / chronic allograft rejection among cardiac, lung and renal transplant recipients is considered investigational.
MEDICAL APPROPRIATENESS
Extracorporeal photochemotherapy / photopheresis is considered medically appropriate if ANY ONE of the following criteria are met:
An individual has early stage I/II (T1 and T2) cutaneous T-cell lymphoma and ALL of the following criteria are met:
The disease is progressive
The disease is refractory to established nonsystemic therapies
An individual has late stage III (T3) cutaneous T-cell lymphoma (CTCL) and ALL the following are met:
The disease is refractory
At least two standard therapies have been attempted and failed (e.g., psoralen + ultraviolet A radiation [PUVA], total-skin electron-beam radiation therapy [TSEBRT], interferon, nitrogen mustard, or a combination of these therapies)
ECP may be used after total skin electron beam radiation therapy (TSEBRT) for reduction of relapse and improved overall survival
Absence of ECP as monotherapy for late stage III (T3)
An individual has late stage IV( T4) CTCL and ALL of the following are met:
The disease is refractory
At least two standard therapies have been attempted and failed (e.g., psoralen + ultraviolet A radiation [PUVA], total-skin electron-beam radiation therapy [TSEBRT], interferon, nitrogen mustard, or a combination of these therapies)
Has general erythroderma for which ECP is a first line treatment
An individual has GVHD and ALL of the following are met:
The disease is chronic
The disease is refractory to established medical therapy (e.g., alternating regimen of cyclosporine and prednisone, or corticosteroid monotherapy, or cytotoxic immunosuppressive drugs [e.g., procarbazine, cyclophosphamide, and azathioprine])
ADDITIONAL INFORMATION
ECP is delivered on 2 consecutive days every four weeks for 6 to 8 months to assess for a response. If an individual is responsive, ECP continues for up to more than one year and less than three years (12 to 36 ECP 2-day cycles). Individuals are weaned off of ECP by increasing the intervals between ECP cycles. When the interval reaches 8 weeks for three consecutive cycles the treatment is usually stopped with only a small risk of relapse.
Other treatment options should be considered for those individuals that do not show a response to ECP by 6 to 8 months.
Cutaneous T-cell lymphoma (CTCL) is a broad term that includes all malignancies of the T lymphocyte where the skin is the primary organ of involvement. Mycosis fungoides, the most common variant, behaves as a low grade non-Hodgkin's lymphoma (NHL) with median survivals in excess of 8 years in most early stage individuals whereas Sézary syndrome, the second most common variant, behaves as an intermediate grade NHL with a median survival of 30 months.
A form of the Tumor, Node, and Malignancy (TNM) classification system is used to stage cutaneous T-cell lymphoma (CTCL). The staging classes includes: T0 for lesions clinically and/ or histopathologically suggestive of CTCL, T1 (stage 1) for limited plaques, papules or eczematous patches covering less than 10% of skin surface, T2 (stage 2) is generalized plaques, papules, or erythematous patches covering 10% or more of skin surface, T3 (stage 3) classifies cutaneous tumors and T4 (stage 4) is for generalized erythroderma.
Other treatments for CTCL are TSEBRT, PUVA, topical mechlorethamine (i.e., nitrogen mustard), interferon alfa alone or in combination with topical therapy, systemic chemotherapy (single agent or combination) often combined with treatment directed at the skin, fludarabine, and retinoids.
Well-designed studies in peer reviewed literature regarding extracorporeal photochemotherapy / photopheresis for conditions listed in the policy statement as investigational are lacking. Therefore, the effects of the technology on health outcomes and whether net health outcome is improved are not known.
SOURCES
Arulogun, S., Prince, H., Gambell, P., Lade, S., Ryan, G., Eaton, E., et al. (2008). Extracorporeal photopheresis for the treatment of Sezary syndrome using a novel treatment protocol. Journal of American Academy of Dermatology, 59 (4), 589 - 595. (Level 4 Evidence)
BlueCross BlueShield Association. Medical Policy Reference Manual. (12:2008). Extracorporeal Photopheresis as a treatment of graft vs. host disease, autoimmune disease, and cutaneous T-cell lymphoma (8.01.36). Retrieved May 20, 2009 from BlueWeb.
Burg, G., Kempf, W., Cozzio, A., Feit, J., Willemze, R., Jaffe E, et al. (2005). WHO-EORTC classification for cutaneous lymphomas. Journal of Cutaneous Pathology, 32(10), 647 - 74. (Level 5 Evidence)
Complete Guide to Medicare Coverage Issues [Computer software]. (2009, April). Extracorporeal photopheresis (NCD 110.4, p. 2-51 - 2-52). The Ingenix Complete Guide to Medicare Coverage Issues.
Di Renzo, M., Sbano, P., De Alo, G., Pasqui, A., Rubegni, P., Ghezzi, A., et al. (2008). Extracorporeal photopheresis affects co-stimulatory molecule expression and interleukin-10 production by dendritic cells in graft-versus-host-disease patients. Clinical and Experimental Immunology, 15 (3), 407 - 413. (Level 4 Evidence)
Flowers, M., Apperley, J., van Besien, K., Elmaagacli, A., Grigg, A., Reddy, V., et al. (2008). A multicenter prospective phase 2 randomized study of extracorporeal photopheresis for treatment of chronic graft-versus-host disease. Blood,112 (7), 2667 - 2674. (Level 2 Evidence)
Hayes. Medical Technology Directory. (2006, August). Extracorporeal photopheresis for the treatment of cutaneous T-cell lymphoma. Retrieved May 26, 2009 from www.Hayesinc.com/subscribers. (38 articles and/or guidelines reviewed)
Keehn, C., Belongie, I., Shistik, G., Fenske, N., & Glass, L. (2007). The diagnosis, staging, and treatment options for mycosis fungoides. Cancer control, 14 (2), 102 - 111. (Level 5 Evidence)
Knobler, R., French, L., Kim, Y., Bisaccia, E., Graninger, W., Nahavandi, H., et al. (2006). A randomized, double-blind, placebo-controlled trial of photopheresis in systemic sclerosis. Journal of American Academy of Dermatology, 54 (5), 793 - 799. (Level 2 Evidence)
National Cancer Institute (2008, May). Mycosis fungoides and the Sézary syndrome. Retrieved May 27, 2009 from http://www.cancer.gov/cancertopics/pdq/treatment/mycosisfungoides/HealthProfessional.
National Comprehensive Cancer Network. (April, 2009). NCCN Clinical practice guidelines in Oncology Non-Hodgkin’s Lymphoma. Retrieved July 10, 2009 from http://www.nccn.org/professionals/physician_gls/PDF/nhl.pdf.
Nihtyanova, S., & Denton, C. (2008). Current approaches to the management of early active diffuse scleroderma skin disease. Rheumatic Diseases Clinics of North America, 34 (1), 161 - 179. (Level 5 Evidence)
Scarisbrick, J., Taylor, P., Holtick, U., Makar, Y., Douglas, K., Berlin, G., et al. (2008). U.K. consensus statement on the use of extracorporeal photopheresis for treatment of cutaneous T-cell lymphoma and chronic graft-versus-host disease. British Journal of Dermatology, 158 (4), 659 - 678. (Level 2 Evidence)
The American Cancer Society. (2008, November). Making Treatment Decisions, Light Therapy. Retrieved May 27, 2009 from http://www.cancer.org/docroot/ETO/content/ETO_5_3X_Light_Therapy.asp?sitearea=ETO .
The Technology Evaluation Center. (2001, November). Extracorporeal photophoresis for graft versus host disease or autoimmune disease. (Vol. 16, No. 9). Chicago: BlueCross BlueShield Association. (45 articles and/or guidelines reviewed)
The Technology Evaluation Center. (2001, November). Extracorporeal photophoresis for the treatment of autoimmune disease. (Vol. 16, No. 10). Chicago: BlueCross BlueShield Association. (63 articles and/or guidelines reviewed)
U. S. Food and Drug Administration. (2008, October). Center for Drug Evaluation and Research. Supplemental biologics license approval BL103767/5094. Retrieved June 4, 2009 from. http://www.accessdata.fda.gov/drugsatfda_docs/appletter/2008/103767s5094ltr.pdf.
Urbani, L., Mazzoni, A., Colombatto, P., Biancofiore, G., Bindi, L., Tascini, C., et al. (2008). Potential applications of extracorporeal photopheresis in liver transplantation. Transplantation Proceedings, 40 (4), 1175 - 1178. (Level 4 Evidence)
Whittaker, S., Marsden, J., Spittle, M., & Jones, R. (2003). Joint British Association of Dermatologists and U. K. Cutaneous lymphoma group guidelines for the management of primary cutaneous T-cell lymphomas. The British Journal of Dermatology, 149 (6), 1095 – 1107. (Level 5 Evidence)
Xia, C., Campbell, K., & Clare-Salzier, M. (2009). Extracorporeal photopheresis-induced immune tolerance: a focus on modulation of antigen-presenting cells and induction of regulatory T cells by apoptotic cells. Current Opinion in Organ Transplantation, (E pub ahead of print). (Level 5 Evidence)
ORIGINAL EFFECTIVE DATE: 3/1/2001
MOST RECENT REVIEW DATE: 10/10/2009
ID_BT
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