Current Treatment of Refractory/Relapsed Chronic Lymphocytic Leukemia: A Focus on Novel Drugs

Recently, the use of novel targeted drugs has changed the treatment paradigms in chronic lymphocytic leukemia (CLL). Among the several drugs used for the management of relapsed/refractory (R/R) CLL, Bruton tyrosine kinase inhibitors (ibrutinib and acalabrutinib), phosphatidylinositol 3-kinase inhibitors (idelalisib and duvelisib), B-cell lymphoma 2 inhibitor (venetoclax), and novel CD20 monoclonal antibodies have demonstrated the greatest improvements in survival among R/R CLL patients. However, patients with relapsed but asymptomatic CLL do not need immediate alternative treatment and should be observed until evident sign of progression. Among available approved treatments, venetoclax + rituximab for 24 months or ibrutinib as continuous therapy is recommended. Another, less recommended, option is idelalisib in combination with rituximab. The correct treatment selection depends on the type of prior therapy, response to previous treatment and side effects, presence of comorbidities, and the risk of drug toxicity. Allogeneic hematopoietic stem cell transplantation and investigational therapies such as chimeric antigen receptor-T-cell therapy are promising treatment options for high-risk patients, including those progressing after 1 or more targeted therapies. The present review discusses current treatment strategies for patients with R/R CLL.