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Oral PI3K-δ,γ Inhibitor for the Management of People with Chronic Lymphocytic Leukemia and Small Lymphocytic Lymphoma: A Narrative Review on Duvelisib

Authors Shah A, Barrientos JC

Received 17 July 2020

Accepted for publication 5 March 2021

Published 25 March 2021 Volume 2021:14 Pages 2109—2119


Checked for plagiarism Yes

Review by Single anonymous peer review

Peer reviewer comments 3

Editor who approved publication: Prof. Dr. Takuya Aoki

Ankit Shah,1 Jacqueline C Barrientos2

1Division of Hematology-Oncology, Department of Medicine at Rutgers New Jersey Medical School, Newark, NJ, USA; 2CLL Research and Treatment Center, Division of Hematology-Oncology, Department of Medicine at Zucker School of Medicine at Hofstra/Northwell, Hempstead, NY, USA

Correspondence: Jacqueline C Barrientos Tel +1-516-470-4050
Fax +1-516-470-4250
Email [email protected]

Abstract: The development of highly effective targeted therapies has led to a new treatment paradigm in patients with chronic lymphocytic leukemia or small lymphocytic lymphoma (CLL/SLL). Despite these advances, many patients will eventually require alternative treatment strategies due to the emergence of tolerability issues or resistance to these novel agents. Duvelisib is a first-in-class, potent oral agent with dual inhibitor activity against the δ and γ isoforms of phosphoinositide 3-kinase (PI3Kδ and PI3Kγ), which are specific to the hematopoietic system. Dysregulation of the PI3K/PTEN/AKT/mTOR pathway has been implicated in cancer cell growth, survival and metabolism and has been the subject of cancer drug development in recent years. Duvelisib demonstrated activity in CLL/SLL in early trials, leading to further evaluation in the Phase 3 DUO trial that compared duvelisib against ofatumumab in patients with relapsed/refractory CLL/SLL. This trial led to the Food and Drug Administration (FDA) approval for the treatment of adult patients with CLL/SLL after at least two prior lines of therapy. The major reason for therapy discontinuation is the development of serious adverse events, which include severe infections and diarrhea/colitis, precluding its widespread use. Ongoing clinical trials are evaluating duvelisib in combination strategies and with alternate dosing schedules in patients with CLL/SLL. With close monitoring, duvelisib can be a promising drug for the treatment of patients with relapsed or refractory CLL/SLL. This review summarizes the relevant clinical data from recent clinical advances in CLL and aims to interpret the duvelisib trials while exploring strategies to improve its use and adverse event management in the era of novel targeted agents.

Keywords: duvelisib, CLL/SLL, PI3K, relapsed/refractory

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