Update on therapy of chronic lymphocytic leukemia

Abstract

There have been tremendous advances in the treatment of chronic lymphocytic leukemia (CLL) over the past decade, with the goal of therapy no longer being just to palliate symptoms but now to achieve complete remission, eradicate minimal residual disease, and improve survival. During this period, there have also been major advances in identification of molecular factors associated with increased risk of progression. The clinical utility of these factors is being explored to determine whether we can identify groups of patients who should be treated earlier in their disease course and whether we can tailor therapy for groups of patients with specific molecular markers of disease. First-line chemoimmunotherapy approaches now offer prolonged survival, and there is a need to identify patients who are suitable candidates for allogeneic stem-cell transplantation that uses reduced-intensity conditioning regimens. The vast majority of CLL patients are either too old or do not have sufficiently high-risk disease to warrant these approaches, and effective therapies that can be tolerated by the more frail elderly patients with this disease are urgently needed. Numerous novel agents are being developed, and their role in the first-line treatment of frail patients or those who relapse after previous treatment is being explored in clinical trials.

Fig 1

Clinical trial evaluating the use of prognostic factors to assess the impact of early therapy in chronic lymphocytic leukemia. Risk factors are used to stratify asymptomatic Binet stage A patients into low and high risk. High-risk patients are randomly assigned to continue with the watch-and-wait approach or to receive therapy with fludarabine, cyclophosphamide, and rituximab. VH, heavy-chain variable gene; LDT, lymphocyte doubling time; TK, thymidine kinase.

Fig 2

How we treat chronic lymphocytic leukemia (CLL). Asymptomatic patients should be treated with a watch-and-wait approach until they are symptomatic, unless they are enrolled onto clinical trials assessing the impact of prognostic features on early treatment. Treatment of choice is fludarabine, cyclophosphamide, and rituximab (FCR), unless there is a suitable clinical trial. Patients with del17p or p53 mutations should be considered for clinical trial and offered reduced-intensity conditioning (RIC) allogeneic stem-cell transplantation (allo-SCT). Patients who are not fit for consideration for FCR should be considered for clinical trials investigating novel approaches for these patients.