What Is Optimal Front-Line Therapy for Chronic Lymphocytic Leukemia in 2017?

opinion statementThe front-line management of patients with chronic lymphocytic leukemia (CLL) has evolved significantly in recent years due to introduction of novel, targeted agents. Upon CLL diagnosis, physicians should determine whether treatment or careful observation is indicated. Once treatment is required, choice of therapy should be based on the age and fitness of the patient and the distinct molecular profile of their disease. As multiple novel agents are in various stages of development, all patients regardless of their age, fitness, and disease risk should be evaluated for clinical trial participation before initiating any front-line therapy. If no clinical trial is available, we provide our recommendations for front-line treatment of CLL patients. Healthy, young patients with low-risk disease (mutated IgVH, del (13q)) should be offered fludarabine, chlorambucil, and rituximab (FCR), while similar patients with high-risk disease (unmutated IgVH, del (17p), del (11q), and complex karyotype) should be considered for ibrutinib therapy. For those young, fit patients with high-risk disease and a contraindication to ibrutinib, FCR, or high-dose methylprednisolone and rituximab are options. In regard to older, unfit patients, a careful assessment of their fitness and ability to tolerate treatment should be undertaken before starting therapy. Those who have poor performance and multiple medical comorbidities should be considered for palliative care alone. However, those who are fit enough for treatment can be offered ibrutinib. If there is a contraindication to ibrutinib, they can be separated into low- and high-risk molecular groups. For the low-risk patients, bendamustine and rituximab or obinutuzumab and chlorambucil can be considered. For the high-risk patients, treatment with rituximab and lenalidomide is an option. Herein, we provide an evidence-based front-line treatment algorithm for CLL patients based upon fitness and molecular risk.