Extracorporeal Photopheresis
DESCRIPTION
Extracorporeal photopheresis (ECP), also known as extracorporeal photochemotherapy, 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.
Researchers are also exploring the possibility that ECP may be utilized in the treatment for and prevention of organ rejection after solid-organ transplant. Studies mainly focus on cardiac transplantation, which little information available regarding liver and kidney transplantation. A regimen of immunosuppressive therapy is standard of care for the treatment of solid-organ rejection. Therefore, refractory rejection is defined as rejection that fails to respond adequately to a standard regimen of immunosuppressive therapy. Recurrent allograft rejection is defined as having at least 2 rejection episodes that recurred after standard immunosuppressive therapy.
POLICY
Extracorporeal 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 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 photopheresis for the treatment of cardiac allograft rejection is considered medically necessary if the medical appropriateness criteria are met. (See Medical Appropriateness below.)
Extracorporeal photopheresis for the treatment or prevention of other conditions/diseases, including, but not limited to, the following is considered investigational:
Systemic lupus erythematosus
Multiple sclerosis
Rheumatoid arthritis
Pemphigus vulgaris
Scleroderma
Acute / chronic GVHD that is either previously untreated or is responding to established therapies
Rejection of solid-organ transplantation (e.g., lung, liver, pancreas, kidney).
Any device utilized for this procedure must have FDA approval specific to the indication, otherwise it will be considered investigational.
MEDICAL APPROPRIATENESS
Extracorporeal photopheresis is considered medically appropriate if ANY ONE of the following criteria are met:
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
Late stage III (T3) cutaneous T-cell lymphoma (CTCL) and ALL the following criteria 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)
Late stage IV( T4) cutaneous T-cell lymphoma (CTCL) and ALL of the following criteria 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
Graft-versus-host disease (GVHD) and ALL of the following criteria 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])
Cardiac allograft rejection and ANY ONE of the following criteria are met:
The rejection is recurrent
The rejection is refractory to standard immunosuppressive drug treatment
IMPORTANT REMINDER
We develop Medical Policies to provide guidance to Members and Providers. This Medical Policy relates only to the services or supplies described in it. The existence of a Medical Policy is not an authorization, certification, explanation of benefits or a contract for the service (or supply) that is referenced in the Medical Policy. For a determination of the benefits that a Member is entitled to receive under his or her health plan, the Member's health plan must be reviewed. If there is a conflict between the Medical Policy and a health plan, the express terms of the health plan will govern.
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 total-skin electron-beam radiation therapy (TSEBRT), psoralen + ultraviolet A radiation (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 photopheresis (ECP) 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. ECP as treatment for and prevention of organ rejection and after solid-organ transplant lends itself well to randomized, controlled trials comparing immunosuppressive therapy alone to immunosuppressive therapy with ECP.
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. (3:2010). Extracorporeal photopheresis as treatment for and prevention or organ rejection after solid-organ transplant (8.01.51). Retrieved February 15, 2011 from BlueWeb. (25 articles and/or guidelines reviewed)
BlueCross BlueShield Association. Medical Policy Reference Manual. (12:2009). Extracorporeal photopheresis as a treatment of graft-versus-host disease, autoimmune disease, and cutaneous T-cell lymphoma (8.01.36). Retrieved February 15, 2011 from BlueWeb. (26 articles and/or guidelines reviewed)
Complete Guide to Medicare Coverage Issues [Computer software]. (2010, April). Extracorporeal photopheresis (NCD 110.4, p. 2-52). Ingenix.
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; last update search August 2010). Extracorporeal photopheresis for the treatment of cutaneous T-cell lymphoma. Retrieved August 5, 2010 from www.Hayesinc.com/subscribers. (38 articles and/or guidelines reviewed)
Hivelin, M., Siemionow, M., Grimbert, P., & Lantieri, L. (2009). Extracorporeal photopheresis: From solid organs to face transplantation. Transplant Immunology, 21 (3), 117-128. Abstract retrieved February 15, 2011 from PubMed database.
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)
Marques, M. B., & Tuncer, H. H. (2006). Photopheresis in solid organ transplant rejection. Journal of Clinical Apheresis, 21 (1), 72-77. Abstract retrieved February 15, 2011 from PubMed database.
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)
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)
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: 7/9/2011
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