Understanding TreatmentOptions in
Cutaneous Lymphoma
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15
Cutaneous T-Cell Lymphomas
2
Antibodies
Monoclonal antibodies are themost common biologic agents used for
lymphoma therapy.The immune system uses antibodies to recognize and
destroy foreign invaders such as bacteria and viruses. Scientists cannowproduce
“monoclonal antibodies” in the laboratory that recognize certain kinds of
cancer cells.Once in the blood,monoclonal antibodies travel throughout the
body and attach themselves to their specific target.Antibodies are thought
towork by stopping or slowing the growth of cancer cells, or bymaking it
easier for the person’s immune system todestroy the tumor cell.Healthy cells
can also be affected by the antibody, but the body can usually replace these
cells after the treatment with biologic therapy has stopped.However, patients
taking a biologic treatmentmay be susceptible to infection.Alemtuzumab
(Campath®) is amonoclonal antibody that targets theCD52 antigen on the
cell surface of cancerous lymphocytes.Alemtuzumab can be given as a low-dose
regimen that can reducemalignantT cellswithout affectinghealthyT cells.
39-43
Mogamulizumab, a bioengineered, humanizedmonoclonal antibody against
CCR4, is a newer antibody treatment being tested inCTCL.
44
Monoclonal antibodies can also bemadewith a chemotherapy drug, radioactive
particle, or toxin attached to it.These antibodies bring the drug, radioactive
particle, or toxin to its target on themalignant cell.One example of this is
brentuximab vedotin (Adcetris®), amonoclonal antibody that targets theCD30
antigen on cancer cells.
45
This antibody is attached to a drug (monomethyl
auristatinE) that can kill the cancer cell after the antibody attaches to it.
Common side effects experienced by patients receiving brentuximabwere
fatigue, fever, diarrhea, andnausea.This drug is being tested inprimary
cutaneousCD30-positiveCTCLs.
46
Denileukindiftitox is a “fusionprotein,”meaning that it ismade of 2different
molecules: a biologic agent called interleukin 2 anddiphtheria toxin.
45
The
interleukin 2 attaches to the cancer cell, and the diphtheria toxin kills the
cell.Denileukindiftitox is used to treat persistent or recurrentCD25-positive
CTCL.The supply of denileukindiftitox (Ontak®) for general use is onhold
and it is currently available only through a clinical trial.
Targeted Therapy
HistoneDeacetylases
Histone deacetylase (HDAC) inhibitors like vorinostat (capsule)
47,48
and
romidepsin (intravenous)
49
are a newer group of drugs that are thought to
work by blocking enzymes in cells calledhistone deacetylases. Stopping these
enzymes changes the amount of proteinsmade in cells,which affects the
rate at which these cells can grow anddivide.TheFDA approved vorinostat,
which showed a 30% response rate inpatientswithCTCLhighly resistant to
therapy; however, the duration of response ismixed and limited.
47
There are
also serious side effects associatedwith treatment, including diarrhea, nausea,
and thrombocytopenia (lowplatelets).Romidepsin, also approved by theFDA
for treatment ofCTCL,
50
showed 40% responses inCTCLhighly resistant
to therapywithhigher duration of response, sometimes exceeding 20months.
Clearing of skin lesions and blood andnodal diseasewas also observed in
patientswith advanced forms ofCTCL.
Chemotherapy
Most chemotherapy drugs forCTCLhave been in use for decades, but several
have beendevelopedmore recently.While these agents are frequently used
in combination for the treatment ofmany cancers, they aremostly used in
CTCL as “single agents,”meaning they are given independently.Chemotherapy
agents used forCTCL includemethotrexate (an anti-metabolite), liposomal
doxorubicin,
51
cyclophosphamide, and gemcitabine
52
(agents that interfere
with theDNA of cancer cells), pentostatin (a kind of antibiotic), chlorambucil,
etoposide, temozolomide, andpralatrexate.
53
Combination chemotherapies are
reserved for patientswhose disease does not respond to single agents or for
selectedpatientswhohave solid organ involvement.More information on the
details of each agent can be found at
.
