Some cancer experts believe that chemotherapy and other drugs used in the management of chronic lymphocytic leukemia (CLL) should not be given to patients with early-stage disease until they experience signs or symptoms, to spare them the side effects associated with treatment. According to some of these experts, a number of patients with early-stage CLL may never need therapy.
If the decision is made to treat an asymptomatic patient with early-stage CLL, the drug(s) used should be safe and well-tolerated, with the goal of slowing disease progression and extending overall survival. However, results from older clinical trials have shown that chemotherapeutic drugs (eg, single-agent chlorambucil or the 3-drug combination of fludarabine, cyclophosphamide, and rituximab) cause troubling side effects and do not extend overall survival in patients with early-stage disease. For this reason, cancer specialists, known as oncologists, do not recommend chemotherapy for these patients.
Researchers are now exploring whether the use of targeted agents can be helpful in the treatment of patients with early-stage CLL. Ibrutinib (Imbruvica; Pharmacyclics), an oral first-generation Bruton tyrosine kinase inhibitor, is one of several novel drugs that are FDA-approved for use in patients with CLL who have symptoms and require treatment. To determine which patients with CLL need treatment, oncologists use guidelines that have been developed by the International Workshop on Chronic Lymphocytic Leukemia (iwCLL).
One unresolved question is whether earlier treatment of CLL with ibrutinib or similar drugs is worthwhile. All treatments, including ibrutinib, are associated with side effects and pose safety risks. In patients with CLL, ibrutinib can cause diarrhea, bruises, and high blood pressure. Bleeding in the brain and weakening of the immune system are examples of more serious side effects associated with this drug.
Results from clinical trials are beginning to provide insight. In the German CLL12 study, which enrolled >300 patients with previously untreated early-stage (Binet A Stage) CLL, researchers found that ibrutinib significantly extended event-free survival, progression-free survival, and time to next treatment, compared with a “watch and wait” approach. They also reported that there were no significant differences in the rates of side effects between the 2 arms of the study.
Even before these encouraging results were published, experts had suggested that oncologists consider using newer drugs, such as ibrutinib, for patients with early-stage CLL, regardless of whether symptoms were present. One expert stated, “There are risks to inaction. [Doctors should] consider early intervention…for patients who do not yet meet iwCLL treatment criteria.” Longer-term data from CLL12 and other studies of targeted agents in patients with early-stage CLL will continue to evolve over the next several years.
Patients and their families who are interested in clinical trials evaluating novel targeted drugs for early-stage CLL can talk with their oncologists and visit www.ClinicalTrials.gov to learn more about available options.