PI3-kinase inhibitors in chronic lymphocytic leukemia

Julie E. Chang, Brad S. Kahl

Research output: Contribution to journalReview article

21 Scopus citations

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.

Original languageEnglish
Pages (from-to)33-43
Number of pages11
JournalCurrent Hematologic Malignancy Reports
Volume9
Issue number1
DOIs
StatePublished - Mar 1 2014
Externally publishedYes

Keywords

  • CAL-101
  • Chronic lymphocytic leukemia
  • GS-1101
  • INK-1197
  • IPI-145
  • Idelalisib
  • New targets
  • PI3K
  • PI3K Gamma
  • PI3K delta
  • PI3K-γ
  • PI3K-δ
  • Small lymphocytic lymphoma

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