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Current Hematologic Malignancy Reports
Published in: Current Hematologic Malignancy Reports 1/2014

01-03-2014 | Chronic Leukemias (S O'Brien, Section Editor)

PI3-Kinase Inhibitors in Chronic Lymphocytic Leukemia

Authors: Julie E. Chang, Brad S. Kahl

Published in: Current Hematologic Malignancy Reports | Issue 1/2014

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Abstract

The phosphatidylinositol 3-kinase (PI3K) pathway is being explored as a target of inhibition for B-cell lymphoproliferative disorders, with agents specific for inhibition of the PI3K-δ subunit showing significant clinical activity in chronic lymphocytic leukemia (CLL). Idelalisib (CAL-101, GS-1101) and IPI-145 (INK-1147) are novel oral PI3K-δ inhibitors in development, with rates of objective response of 40-60 % and nodal responses exceeding 70 % in relapsed and refractory CLL. High rates of response have been seen in high-risk CLL (i.e., 17p and 11q deletions), and may allow for more effective therapy in inherently chemotherapy-resistant disease. Combination chemotherapy regimens with idelalisib have similarly demonstrated favorable tolerability and activity. Like other agents that target the B-cell receptor pathway, peripheral lymphocytosis, due to drug-induced changes in lymphocyte trafficking, is common. Noteworthy toxicities include transaminitis and pneumonia/pneumonitis. Multiple studies are evaluating PI3K-δ inhibitor combination regimens, and the rationale for these ongoing and planned studies is reviewed.
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Metadata
Title
PI3-Kinase Inhibitors in Chronic Lymphocytic Leukemia
Authors
Julie E. Chang
Brad S. Kahl
Publication date
01-03-2014
Publisher
Springer US
Published in
Current Hematologic Malignancy Reports / Issue 1/2014
Print ISSN: 1558-8211
Electronic ISSN: 1558-822X
DOI
https://doi.org/10.1007/s11899-013-0189-7

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