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Idelalisib is an orally available, highly selective PI3Kδ small molecule inhibitor identified in kinome-wide screening assays. The PI3K p110δ isoform inhibitor idelalisib was the first agent in a new class of isoform-specific inhibitors to receive regulatory approval. Approved FDA indications for idelalisib include relapsed chronic lymphocytic leukemia (CLL) in combination with rituximab in comorbid patients and relapsed follicular lymphoma (FL) with 2 or more prior therapies.
This article was written by Chan Yoon Cheah and Nathan Fowler from Sir Charles Gairdner Hospital, Perth and University of Texas MD Anderson Cancer Centre Houston, Texas, respectively; published in the Journal Blood in July 2016 highlighting the rationale for targeting pathways, representing safety and efficacy data with idelalisib in patients with lymphoma, describing toxicities of the agent in combination studies and the mechanisms of resistance to idelalisib.1
The article describes an important treatment option for patients with relapsed/refractory indolent B-cell lymphoma. Most of the adverse events were manageable. Use of other PI3K isoform inhibitors are currently under development. Careful design and optimal combinations of idelalisib with other agents need to be established.
Idelalisib in the management of lymphoma
Inhibition of the phosphatidylinositol-3-kinase (PI3K) pathway as an anticancer therapeutic strategy was realized with the approval of the orally bioavailable small molecule PI3Kδ inhibitor idelalisib. In this focused review, we highlight the rationale for targeting the pathway in lymphomas, provide a brief summary of the preclinical data, and describe the clinical experience with this agent in patients with lymphoma. We describe some of the idiosyncratic toxicities of this agent, some of the mechanisms of resistance, and some of the ongoing combination strategies.
The complete article can be found here.
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