Am J Clin
Treatment of cutaneous T cell lymphoma: current status and future
N, Talpur R, Duvic M.
Division of Internal Medicine, Department of Dermatology, University
of Texas, MD Anderson Cancer Center, 1515 Holcombe Boulevard,
Houston, TX 77030, USA.
The treatment of cutaneous T cell lymphoma (CTCL), which includes
mycosis fungoides and Sezary syndrome, has been in a state of
continual change over recent decades, as new therapies are
constantly emerging in the search for more effective treatments for
However, prognosis and survival of
patients with CTCL remains dependent upon overall clinical stage
(stage IA-IVB) at presentation, as well as response to therapy.
Past therapies have been limited by
toxicity or the lack of consistently durable responses, and few
treatments have been shown to actually alter survival, especially in
the late stages of disease.
Even aggressive chemotherapy has not
been shown to improve overall survival compared to conservative
sequential therapy in advanced disease, and adds the risk of
immunosuppressive complications. Over the last decade,
extracorporeal photopheresis -
(ECP) is a leukapheresis-based
immunomodulatory therapy that has been Food and Drug
Administration (FDA) approved for the treatment of cutaneous
T-cell lymphoma (CTCL) since 1988. ECP is performed in more that
150 locations worldwide. With the long-term follow-up data
currently available from multiple centers, it is clear that ECP
provides significant disease remission and prolongation of life in
patients with CTCL. In addition, ECP has been effective in the
prevention and reversal of solid organ transplant rejection and
graft-vs-host disease (GvHD). ECP use in the treatment of many
autoimmune diseases also is being explored. - emedicine
has been the only single treatment
that has been shown to improve survival in patients with Sezary
syndrome, although its true efficacy and place in combination
therapy remain unclear.
Much of the focus of current research
has been on combinations of skin-directed therapies and biological
response modifiers, which improve response rates. The results of
various trials over the years have also brought into favor the use
of post-remission maintenance therapy with topical corticosteroids,
topical mechlorethamine (nitrogen mustard), interferon-alpha, or
phototherapy to prevent disease relapse.
Recent novel developments in CTCL
oral bexarotene, a retinoid X
receptor-selective retinoid that has activity in all stages of CTCL,
and the topical gel formulation of
bexarotene, which plays a role in treating localized lesions.
US Food and Drug Administration
(FDA)-approved, oral systemic bexarotene has the advantage of a 48%
overall response rate at a dosage of 300 mg/m(2)/day, and avoids
immunosuppression and risk of central line and catheter-related
infectious complications that are associated with other systemic
therapies. Monitoring of triglycerides and use of concomitant
lipid-lowering agents and thyroid replacement is required in most
Also recently FDA-approved, denileukin
diftitox is the first of a novel class of fusion toxin proteins and
is selective for interleukin-2R (CD25+) T cells, targeting the
malignant T cell clones in CTCL. Denileukin diftitox is associated
with capillary leak syndrome in 20 to 30% of patients, which may be
ameliorated by hydration and corticosteroids.
Higher response rates are possible by
combining bexarotene with "statin" drugs and active CTCL
therapies. Studies are being conducted on combining bexarotene and
denileukin diftitox with other modalities.
Biological response modifier therapies
that are in current or future investigational trials include topical
tazarotene, pegylated interferon, interleukin-2, and interleukin-12.
At the forefront of systemic
chemotherapy development, pegylated liposomal doxorubicin,
gemcitabine, and pentostatin appear to have the greatest potential
for success in CTCL therapy. Bone marrow transplantation, which is
currently limited by the risk of graft-versus-host disease, offers
the greatest potential for disease cure. Further developments for
CTCL may include more selective immunomodulatory agents, vaccines,
and monoclonal antibodies.
PMID: 11978140 [PubMed