Duvelisib (Copiktra) in relapsed or refractory chronic lymphocytic leukemia: safety and efficacy

Introduction: The treatment landscape of chronic lymphocytic leukemia (CLL) has changed dramatically with the introduction of novel targeted therapies. Phosphoinotiside-3 kinase (PI3K) is a B-cell receptor-associated kinase that is essential for growth, survival and migration of neoplastic B cells and is implicated in disease progression and drug resistance. Area covered: PI3K inhibitors idelalisib and duvelisib are approved in therapy of relapsed/refractory (R/R) CLL. In this drug profile review, we focus on duvelisib, an oral inhibitor of PI3Kδ and PI3Kγ isoforms, in treatment of patients with R/R CLL. Expert opinion: Duvelisib, a selective dual PI3Kδ/γ inhibitor, achieves meaningful efficacy in CLL, including in patients with high-risk features. Duvelisib therapy may be particularly appropriate for patients who are suboptimal candidates for Bruton tyrosine kinase inhibitors (BTK), such as those with cardiac conditions, poorly controlled hypertension, or requiring full-dose anticoagulation. Tumor lysis monitoring is not necessary with duvelisib, rendering advantage over the BCL2 inhibitor venetoclax. Patients who progress on both BTK inhibitors and venetoclax may be particularly good candidates for duvelisib therapy. With close monitoring and management of adverse events, duvelisib will continue to have a role in therapy of R/R CLL.