Coverage Policy Manual
Policy #: 2003007
Category: Medicine
Initiated: June 2003
Last Review: August 2018
  Photochemotherapy, Extracorporeal (Photopheresis) as a Treatment of Cutaneous T-Cell Lymphoma

Description:
Extracorporeal photopheresis (ECP) is a leukapheresis-based immunomodulatory procedure that involves the following steps:
 
  1. Patient blood is collected into a centrifuge system that separates the leukocyte-rich portion (buffy coat) from the rest of the blood.
  2. The photosensitizer agent 8-methoxypsoralen (8-MOP) is added to the lymphocyte fraction, which is then exposed to ultraviolet (UV) A (320-400 nm wavelength) light at a dose of 1-2 J per square cm.
  3. The light-sensitized lymphocytes are reinfused into the patient.
 
ECP has been investigated for the treatment of patients with a variety of autoimmune diseases, graft-versus-host disease (GVHD), T-cell lymphoma (TCL), treatment for and prevention of organ rejection after solid-organ transplant and other miscellaneous conditions.
 
This policy addresses ECP for the treatment of cutaneous T-cell lymphoma only.
 
Cutaneous T-Cell Lymphoma (CTCL)
 
According to the National Cancer Institute (NCI), CTCL is a neoplasia of malignant T lymphocytes that initially present as skin involvement. CTCL is extremely rare, with an estimated incidence of approximately 0.4 per 100,000 annually but, because most are low-grade malignancies with long survival, the overall prevalence is much higher. Two CTCL variants, mycosis fungoides and the Sezary syndrome, account for approximately 60% and 5% of new cases of CTCL, respectively.
 
CTCL is included in the Revised European-American Lymphoma classification as a group of low-grade T-cell lymphomas, which should be distinguished from other T-cell lymphomas that involve the skin, such as anaplastic large-cell lymphoma, peripheral T-cell lymphoma, adult T-cell leukemia/lymphoma (usually with systemic involvement), or subcutaneous panniculitic T-cell lymphoma. In addition, a number of benign or very indolent conditions can be confused with mycosis fungoides, further complicating diagnosis. See the Policy Guidelines for the current staging classification of CTCL using the tumor, node, metastasis (TNM) classification system.
 
Mycosis fungoides typically progress from an eczematous patch/plaque stage, covering less than 10% of the body surface (T1), to a plaque stage, covering 10% or more of the body surface (T2), and finally to tumors (T3) that frequently undergo necrotic ulceration. Sezary syndrome is an advanced form of mycosis fungoides with generalized erythroderma (T4) and peripheral blood involvement (B1) at presentation. Cytologic transformation from a low-grade lymphoma to a high-grade lymphoma sometimes occurs during the course of these diseases and is associated with a poor prognosis. A common cause of death during the tumor phase is sepsis from Pseudomonas aeruginosa or Staphylococcus aureus caused by chronic skin infection with staphylococcus species and subsequent systemic infections.
 
The natural history of mycosis fungoides is typically indolent. Symptoms may present for long periods, an average of 2 to 10 years, as waxing and waning cutaneous eruptions prior to biopsy confirmation. The prognosis of patients with mycosis fungoides/Sezary syndrome is based on the extent of disease at presentation and its stage. Lymphadenopathy and involvement of peripheral blood and viscera increase in likelihood with worsening cutaneous involvement and define poor prognostic groups. The median survival following diagnosis varies according to stage. Patients with stage IA disease have a median survival of 20 or more years, with the majority of deaths for this group typically unrelated to mycosis fungoides. In contrast, more than 50% of patients with stage III through stage IV disease die of their disease, with a median survival of less than 5 years.
 
Appropriate therapy of CTCL depends on a variety of factors, including stage, the patient's overall health, and the presence of symptoms. In general, therapies can be categorized into topical and systemic treatments that include ECP. In contrast to more conventional lymphomas, CTCL, possibly excepting ones in the earliest stages, is not curable. Thus, systemic cytotoxic chemotherapy is avoided except for advanced-stage cases. Partial or complete remission is achievable, although the majority of patients require lifelong treatment and monitoring.
 
ECP for the treatment of other disorders are addressed in the following separate policies:
 
Policy #2002026 Photochemotherapy, Extracorporeal (Photopheresis) as a Treatment of Autoimmune Disease
Policy #2002004  Photochemotherapy, Extracorporeal (Photopheresis) as a Treatment of Graft-versus-Host Disease
Policy #2003008  Photochemotherapy, Extracorporeal (Photopheresis) as a Treatment to Prevent Rejection Following Solid-Organ Transplant.
 
 

Policy/
Coverage:
Meets Primary Coverage Criteria Or Is Covered For Contracts Without Primary Coverage Criteria
 
Photochemotherapy, extracorporeal meets primary coverage criteria for effectiveness and is covered for the treatment of cutaneous T-cell lymphoma.

Rationale:
The initial report on the use of ECP as therapy for cutaneous T-cell lymphoma (CTCL) was published by Edelson and colleagues (Edelson, 1987). Twenty-seven of 37 (73%) patients with otherwise resistant CTCL responded to the treatment, with an average 64% decrease in cutaneous involvement after 22 + 10 weeks (mean + SD). The responding group included 8 of 10 (80%) patients with lymph-node involvement, 24 of 29 (83%) with exfoliative erythroderma and 20 of 28 (71%) whose disease was resistant to standard chemotherapy. Side effects that often occur with standard chemotherapy, such as bone marrow suppression, gastrointestinal erosions, and hair loss, did not occur. These results showed that ECP is safe and effective in advanced, resistant CTCL. Subsequent results from numerous small, nonrandomized studies have been generally consistent with the initial conclusion that ECP treatment can produce clinical improvement and may prolong survival in a substantial proportion of patients with advanced-stage CTCL (Frieman, 2006; Keehn, 2007; Knobler, 2004; Scarisbrick, 2006; Whittaker, 2007).
 
2008 Update
Review of peer reviewed medical literature through July 2008 provided no information which would change the above coverage policy.
 
2012 Update
A search of the MEDLINE database conducted through July 2012 did not reveal any new information that would prompt a change in the coverage statement.
 
2013 Update
A search of the MEDLINE database through July 2013 did not reveal any new literature that would prompt a change in the coverage statement.
 
2014 Update
A literature search conducted through July 2014 did not reveal any new information that would prompt a change in the coverage statement. The key identified literature is summarized below.
 
The initial report on the use of ECP as therapy for cutaneous T cell lymphoma (CTCL) was published by Edelson et al in 1987 (Edelson, 1987). Twenty-seven (73%) of 37 patients with otherwise resistant CTCL responded, with a mean 64% decrease in cutaneous involvement after a mean (SD) of 22 (10) weeks. Responders included 8 (80%) of 10 patients with lymph node involvement, 24 (83%) of 29 with exfoliative erythroderma, and 20 (71%) of 28 whose disease was resistant to standard chemotherapy. Adverse effects of standard chemotherapy, such as bone marrow suppression, gastrointestinal erosions, and hair loss, did not occur. In 2012, Knobler et al reanalyzed these data using current response criteria and reported no change in overall response rate (Knobler, 2012). Response was defined as 90% or greater (near CR) or 50% or greater (PR) improvement in skin score for 4 weeks; in the original study, response was defined as 25% or greater improvement for 4 weeks. With 7 years of follow-up, median OS was 9 years from diagnosis and 7 years from the start of ECP. (Mean age at study entry was 57 years [range, 24-80]). These results showed that ECP is safe and effective in advanced, resistant CTCL.
 
Practice Guidelines and Position Statements
National Comprehensive Cancer Network 2014 guidelines for the treatment of CTCL recommend the use of ECP alone or in combination with other agents (retinoids, interferon alfa, denileukin diftitox) as first-line systemic therapy for advanced (stages III/IV) disease, as well as for patients with either earlier stage mycosis fungoides with Sézary syndrome involvement or disease that has failed multiple courses of topical skin-directed treatments. For patients with mycosis fungoides or Sézary syndrome, “photopheresis may be more appropriate as systemic therapy in patients with some blood involvement (B1 [<1000/mm3 Sézary cells or <20% atypical T-cells on peripheral smears] or B2 [leukemic]).” The guidelines do not address the use of ECP for peripheral T cell lymphoma (NCCN, 2014).
 
2015 Update
A literature search conducted through May 2015 did not reveal any new information that would prompt a change in the coverage statement.  
  
2018 Update
Annual policy review completed with a literature search using the MEDLINE database through July 2018. No new literature was identified that would prompt a change in the coverage statement.  
  

CPT/HCPCS:
36522Photopheresis, extracorporeal

References: Edelson R, Berger C, Gasparro F et al.(1987) Treatment of cutaneous T-cell lymphoma by extracorporeal photochemotherapy. Preliminary results. N Engl J Med 1987; 316(6):297-303.

Edelson R, Berger C, Gasparro F et al.(1987) Treatment of cutaneous T-cell lymphoma by extracorporeal photochemotherapy. Preliminary results. N Engl J Med 1987; 316(6):297-303.

Fraser-Andrews E, Seed P, Whittaker S, et al.(1998) Extracorporeal photopheresis in Sézary syndrome: no significant effect in the survival of 44 patients with a peripheral blood T cell clone. Arch Derm 1998; 134:1001-05.

Freiman A, Sasseville D.(2006) Treatment of mycosis fungoides: overview. J Cut Med Surg 2006; 10(5):228-33.

Heald P, Rook A, Perez M, et al.(1992) Treatment of erythrodermic cutaneous T cell Lymphoma with extracorporeal photochemotherapy. J Am Acad Derm 1992; 27:427-433.

Keehn CA, Belongie IP, Shistik G et al.(2007) The diagnosis, staging, and treatment options for mycosis fungoides. Cancer Control 2007; 14(2):102-11.

Knobler E.(2004) Current management strategies for cutaneous T-cell lymphoma. Clin Dermatol 2004; 22(3):197-208.

Knobler R, Duvic M, Querfeld C et al.(2012) Long-term follow-up and survival of cutaneous T-cell lymphoma patients treated with extracorporeal photopheresis. Photodermatol Photoimmunol Photomed 2012; 28(5):250-7.

Lim HW, Edelson Rl.(1995) Photopheresis for the treatment of cutaneous T-cell lymphoma. Hematol Oncol Clin N Am 1995; 9:1117-26.

Scarisbrick JJ.(2006) . Staging and management of cutaneous T-cell lymphoma. Clin Exp Dermatol 2006; 31(2):181-6.

Whittaker SJ, Foss FM.(2007) Efficacy and tolerability of currently available therapies for the mycosis fungoides and Sezary syndrome variants of cutaneous T-cell lymphoma. Cancer Treat Rev 2007; 33(2):146-60.

Zackheim HS.(1999) Cutaneous T cell Lymphoma: Update of treatment. Derm 1999; 199:102-5.


Group specific policy will supersede this policy when applicable. This policy does not apply to the Wal-Mart Associates Group Health Plan participants or to the Tyson Group Health Plan participants.
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