CAR T-cell therapy for CLL: a new addition to our treatment toolbox?

Treatment of high-risk chronic lymphocytic leukemia (CLL) has undergone a revolution in recent years with the introduction of novel agents. Bruton kinase inhibitors (BTK) inhibitors, such as ibrutinib, acalabrutinib, and zanubrutinib, are effective at controlling CLL in all lines of therapy, including in patients with high-risk features. BTK inhibitors can be used in sequence or in combination with the BCL2 inhibitor venetoclax. As a result, standard chemotherapy and allogeneic stem cell transplant (allo-SCT)-once major treatment approaches in high-risk patients-are used much less commonly in the current era. Despite the outstanding efficacy of these novel agents, a proportion of patients still experience disease progression. Chimeric antigen receptor (CAR) T-cell therapy has received regulatory approval for several B-cell malignancies in which it has shown efficacy, but it remains investigational for CLL. Several studies have shown the potential for long-term remission in CLL with CAR T-cell therapy, with a favorable safety profile compared with conventional approaches. This review focuses on selected literature on CAR T-cell therapy for CLL, including the interim results of key ongoing studies, with an emphasis on recent research.