Journal
CURRENT HEMATOLOGIC MALIGNANCY REPORTS
Volume 9, Issue 1, Pages 33-43Publisher
CURRENT MEDICINE GROUP
DOI: 10.1007/s11899-013-0189-7
Keywords
New targets; PI3K; PI3K delta; PI3K-delta; PI3K Gamma; PI3K-gamma; CAL-101; GS-1101; Idelalisib; INK-1197; IPI-145; Chronic lymphocytic leukemia; Small lymphocytic lymphoma
Categories
Funding
- Celgene
- Genentech
- Genentech/Roche
- Millennium
- Infinity
- Gilead
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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-delta subunit showing significant clinical activity in chronic lymphocytic leukemia (CLL). Idelalisib (CAL-101, GS-1101) and IPI-145 (INK-1147) are novel oral PI3K-delta 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-delta inhibitor combination regimens, and the rationale for these ongoing and planned studies is reviewed.
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