PI3-kinase inhibitors in chronic lymphocytic leukemia.
Curr Hematol Malig Rep
; 9(1): 33-43, 2014 Mar.
Article
in En
| MEDLINE
| ID: mdl-24390602
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.
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Leukemia, Lymphocytic, Chronic, B-Cell
/
Protein Kinase Inhibitors
/
Phosphoinositide-3 Kinase Inhibitors
/
Antineoplastic Agents
Limits:
Humans
Language:
En
Journal:
Curr Hematol Malig Rep
Journal subject:
HEMATOLOGIA
/
NEOPLASIAS
Year:
2014
Document type:
Article