New Therapeutic Option In CLL
CLL is the most common form of leukemia in western countries. It is a disease of the elderly. The average age at diagnosis is 70.
It usually presents at stage 0 with isolated lymphocytosis seen on routine blood work. A bone marrow biopsy is no longer necessary to make a diagnosis, since flow cytometry can be performed on peripheral blood smear.
The patients who present with stage 0 may not require treatment for years.
Patients that are symptomatic with anemia, thrombocytopenia, adenopathy and/or hepatosplenomegaly may need immediate therapy.
The goal of treatment is to achieve a complete response. Based on the patient's ability to tolerate therapy, first line single agent treatment with chemotherapy or monoclonal antibodies can be selected.
Chemotherapeutic options include purine analogs like single agent fludarabine, cladribine, and pentostatin have had good complete response rates.
CLL is a B cell malignancy and is commonly CD20+ making such a receptor a good therapeutic target and single agent monoclonal antibodies like rituximab and alemtuzumab have been increasingly popular because of good results and very low side effect profile.
Combination therapy has been reserved for patients able to tolerate higher levels of toxicity. To date, fludarabine, cytoxan and rituximab combination treatment has shown in phase III trials to have the highest complete response rates, disease free survival, and overall survival rates.
Two very effective drugs have emerged in recent years as second line therapies. A chemotherapeutic agent called bendamustine used as a single agent or in combination with rituxan. Ofatumamab is a new monoclonal antibody that also targets the CD20 receptor and was recently FDA approved. Emerging therapies with new mechanism of action are lenalidomide, an immunomodulator used in myeloma, oblimersen a Bcl-2 protein down regulating agent, and lumiliximab, which is directed against CD23 and flavopiridol a cyclin-dependent kinase inhibitor. Great understanding of the disease has resulted in new therapeutic targets that have had an impact on progression free and overall survival.