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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
- Source :
- OncoTargets and therapy
- Publication Year :
- 2021
- Publisher :
- Informa UK Limited, 2021.
-
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.
- Subjects :
- 0301 basic medicine
Oncology
medicine.medical_specialty
Chronic lymphocytic leukemia
Review
Ofatumumab
PI3K
relapsed/refractory
03 medical and health sciences
chemistry.chemical_compound
0302 clinical medicine
hemic and lymphatic diseases
Internal medicine
CLL/SLL
medicine
Pharmacology (medical)
Adverse effect
PI3K/AKT/mTOR pathway
business.industry
medicine.disease
Duvelisib
Discontinuation
Clinical trial
duvelisib
030104 developmental biology
Tolerability
chemistry
030220 oncology & carcinogenesis
business
Subjects
Details
- ISSN :
- 11786930
- Volume :
- 14
- Database :
- OpenAIRE
- Journal :
- OncoTargets and Therapy
- Accession number :
- edsair.doi.dedup.....8e95d3bdbf174007a163fc75afcede59