Challenges in the frontline treatment of patients with chronic lymphocytic leukemia

Therapy for chronic lymphocytic leukemia has improved dramatically over the past 20 years. Traditional therapy with oral chlorambucil led to complete responses in less than 5% of treated patients, in marked contrast to modern regimens, which can reliably produce complete responses in over 50% of patients. This remarkable improvement is attributable to the use of purine analogue-based treatment as well as monoclonal antibodies. Novel combinations of these agents have emerged as effective new therapies for previously untreated patients. Clinical studies indicate that such combinations can induce higher response rates (including complete responses) than single-agent therapy. Those patients who achieve a complete response have superior progression-free survival compared with those who achieve only a partial response. Though not yet demonstrated in a prospective randomized trial, treatment approaches aimed at achieving high-quality responses may one day improve survival for patients with chronic lymphocytic leukemia. However, many challenges remain, such as finding less toxic and equally efficacious regimens for older patients, who remain the majority of the population with this disease.