Chronic Lymphocytic Leukemia - The Leukemia & Lymphoma Society

Chemotherapy. Chlorambucil (Leukeran®) is a long-used form of chemotherapy
for CLL. It is a pill (oral) and remains one standard therapy for older patients (65
years or older). Fludarabine (Fludara®) is considered to be one of the most effective
types of chemotherapy for CLL in younger patients. Drug combinations, including
fludarabine and cyclophosphamide (Cytoxan®) were shown to improve response
and remission time of CLL patients. Fludarabine and cyclophosphamide (FC)
combination therapy is most important for treating the genetic group of CLL with
del (11q). Combination of fludarabine with rituximab (Rituxan®) (FR), a CD20
antibody, (see Monoclonal Antibody Therapy below) or FC with Rituxan (FCR) is
called “chemoimmunotherapy.” Studies comparing treatment with chemotherapy
(fludarabine or FC) with chemoimmunotherapy (FR or FCR) have shown that FR or
FCR treatment significantly improve the frequency of complete response, remission
duration, and overall survival in previously untreated people with CLL (see Treatment
Response and Follow-Up Care on page 22).
While it is clear that FCR is the best treatment for CLL patients with del (11q), the
benefit of this (versus FR) is not as clear in other genetic groups and is currently being
studied in clinical trials. The hesitancy of some doctors to use cyclophosphamide in
FCR, in part, comes from a higher risk that may arise of both short and long-term
complications, such as chronic heart failure. Trials using fludarabine in patients 65
years or older, have not shown as much benefit. Additionally, patients with del (17p)
do not respond as well or for as long to fludarabine-based therapies. Therefore, if del
(17p) is present on a FISH test, it is important for patients to be evaluated early for
consideration of reduced-intensity allogeneic stem cell transplantation or to strongly
consider participating in a clinical trial.
Bendamustine (Treanda®) is another type of chemotherapy that is approved for
the treatment of CLL. Combination therapy with Treanda and Rituxan in both
untreated and previously treated CLL patients have shown promising results and
are commonly being administered as second-line therapy. A randomized trial is
comparing Treanda and Rituxan to FCR in previously untreated CLL patients.
Patients with del (17p) generally do not respond well or for long to Treanda therapy
as initial therapy.
Monoclonal Antibody Therapy. Monoclonal antibodies are proteins that are
bioengineered in the laboratory. Each monoclonal antibody therapy is designed to
recognize a specific molecule on a cell. The monoclonal antibody therapy targets
the molecule and attaches to the cell, causing the cell to die.
The monoclonal antibody therapies rituximab (Rituxan®), ofatumumab (Arzerra®)and
alemtuzumab (Campath®) are used to treat people with CLL (see Table 3 on page 17).
Rituxan and Arzerra target CD20 on the CLL cell’s surface; Campath targets CD52.
Rituxan is FDA approved for combination with fludarabine and cyclophosphamide
in symptomatic, previously untreated and treated CLL. Arzerra is FDA approved for
the treatment of patients with CLL that is refractory to fludarabine and alemtuzumab.
Campath is FDA approved as a single agent for CLL treatment.
Chronic Lymphocytic Leukemia I page 15