Frontline chemotherapy is successful against chronic lymphocytic leukemia (CLL), 
but results in untoward toxicity. Further, prognostic factors, cytogenetic 
anomalies, and compensatory cellular signaling lead to therapy resistance or 
disease relapse. Therefore, for the past few years, development of targeted 
therapies is on the rise. PI3K is a major player in the B-cell receptor (BCR) 
signaling axis, which is critical for the survival and maintenance of B cells. 
Duvelisib, a PI3K δ/γ dual isoform specific inhibitor that induces apoptosis and 
reduces cytokine and chemokine levels in vitro, holds promise for CLL. Areas 
covered: Herein, we review PI3K isoforms and their inhibitors in general, and 
duvelisib in particular; examine literature on preclinical investigations, 
pharmacokinetics and clinical studies of duvelisib either as single agent or in 
combination, for patients with CLL and other lymphoid malignancies. Expert 
opinion: Duvelisib targets the PI3K δ isoform, which is necessary for cell 
proliferation and survival, and γ isoform, which is critical for cytokine 
signaling and pro-inflammatory responses from the microenvironment. In phase I 
clinical trials, duvelisib as a single agent showed promise for CLL and other 
lymphoid malignancies. Phase II and III trials of duvelisib alone or in 
combination with other agents are ongoing.