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Despite the effectiveness of chemoimmunotherapy (CIT), in most cases the clinical course of chronic lymphocytic leukemia (CLL) is characterized by consecutive episodes of disease progression and need for therapy. Treatment possibilities for patients with CLL in whom CIT fails whose disease progresses after initial CIT include pathway inhibitors (PIs) and, for selected patients, cellular therapy (ie, allogeneic stem cell transplant, chimeric antigen receptor T cells). PIs (ie, Bruton tyrosine kinase inhibitors, phosphatidylinositol 3-kinase inhibitors, and BCL2 inhibitors) are revolutionizing the treatment of CLL. PIs have proved to be more effective than CIT, both as upfront therapy and for relapsed/refractory disease, largely because they may overcome the negative impact of adverse biomarkers (eg, TP53 aberrations, unmutated IGHV) on outcomes and because of their acceptable toxicity. In this article, the management of patients with relapsed/refractory CLL is discussed, with a particular emphasis on the role of PIs.

Standard treatment approaches for relapsed/refractory chronic lymphocytic leukemia after frontline chemoimmunotherapy