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    New therapies offer promise for cutaneous T-cell lymphoma

    Durham, N.C. — Some of the continuing challenges central to the management of cutaneous T-cell lymphoma (CTCL) include improving the survival and prognosis of patients, as well as helping to make proposed treatments more affordable and accessible, says Elise A. Olsen, M.D.

    "We do not yet have a cure for CTCL, and treatment is often lifelong to keep the disease under control or in remission. There are not very many treatments for CTCL that are FDA (Food and Drug Administration)-approved at this point, and off-label use is common. In addition, there are some newer therapies that show promise; however, reimbursement in general for treatment of these lymphomas is often lacking or challenging," says Dr. Olsen, professor of dermatology and oncology and director, Cutaneous Lymphoma Research and Treatment Center, Duke University Medical Center, Durham, N.C.

    CTCL subtypes

    The most common subtype of CTCL is mycosis fungoides (MF) and its leukemic counterpart, SÉzary syndrome (SS). Most patients who are diagnosed with MF or SS are over age 50, and many are dependent on Medicare alone to cover treatment, Dr. Olsen says.

    "Because Medicare does not fully cover outpatient medication for long-term use and because some insurance companies fail to reimburse for treatments that are not FDA-approved for that particular indication, many patients with CTCL have difficulty paying for cancer treatment," she says.

    This comes at a time when there are better treatment approaches compared to those of 30 years ago, Dr. Olsen says, adding that these improved therapies result in a more positive prognosis and much longer survival.

    "Today, we choose treatments based on stage of MF/SS and use immunomodulators as first-line therapy," Dr. Olsen says. "We often use combinations of therapies, either one systemic treatment such as interferon alfa or bexarotene, in combination with a skin-directed therapy such as ultraviolet light therapy or topical nitrogen mustard. For more aggressive disease with blood involvement, we may also use extracorporeal photopheresis, and sometimes we use more than one systemic therapy at a time."

    If these immunomodulatory treatments do not work, systemic chemotherapeutic agents could be used, such as one of the histone deacetylase inhibitors recently approved for CTCL or treatments approved for other types of lymphoma (pralatrexate) or one of the monoclonal antibodies (alemtuzumab or brenuximab vedotin). According to Dr. Olsen, these chemotherapies or monoclonal antibodies are best used for certain fixed periods of time. Then alternate chronic treatment with other agents will still need to be pursued.

    CTCL guidelines

    In the United States, the National Comprehensive Cancer Network (NCCN) put forth guidelines that essentially map out what the appropriate treatments are for CTCL. According to Dr. Olsen, these guidelines not only help clinicians choose a uniform treatment approach in CTCL patients; they also help medical insurance companies in their decisions to reimburse appropriate treatment regimens.

    "The therapies that we choose in our CTCL patients are stage-based," she says. "When approaching the CTCL patient, it is crucial to appropriately stage the patient first in order to determine if we are looking at someone who has primarily skin involvement or someone who has extracutaneous disease, as the treatment can be very different according to their stage."

    Even if a patient appears to only have skin involvement, Dr. Olsen says, the type of skin involvement will determine whether the patient has more aggressive disease that can progress toward extracutaneous involvement.

    "For example, patients with a few tumors have a worse prognosis compared to patients with extensive patch stage disease," she says.

    According to Dr. Olsen, deciding which physician is going to see and treat the patient is important to outcome as well. Dermatologists are usually the physicians who make the initial diagnosis, and they may follow and treat these patients throughout their course depending on the patients' initial stage and whether they develop aggressive disease.

    In contrast, oncologists will typically see patients for the first time later in the course of their illness when the disease is more aggressive and/or advanced, she says.

    "We have been working on more cross-talk and more collaboration between the specialties from the time of diagnosis, which has led us to consensus guidelines on staging and approach to therapy," Dr. Olsen says.

    CTCL collaboration

    The United States Cutaneous Lymphoma Consortium (USCLC) is a multidisciplinary nonprofit group of physicians from dermatology, oncology, radiation oncology and pathology who work cooperatively toward improving patient care. According to Dr. Olsen, the USCLC has initiated a national registry for CTCL and plans cooperative clinical trials that can assess the efficacy of agents that are not corporate-sponsored or that are FDA-approved for other indications.

    "The USCLC can also investigate the value of combinations of therapies that would be difficult for the pharmaceutical industry to sponsor. By publishing on the results of such therapies, it makes it much easier for patients to be reimbursed for treatment with them," Dr. Olsen says.

    Disclosures: Dr. Olsen has served as an investigator and has received grants from Esai, Yaupon/Ceptaris and Johnson & Johnson. She also is on the advisory board for Merck, though she is not compensated in that role.

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