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      Idelalisib, an inhibitor of phosphatidylinositol 3-kinase p110δ, for relapsed/refractory chronic lymphocytic leukemia.

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          Abstract

          In a phase 1 trial, idelalisib (GS-1101, CAL-101), a selective inhibitor of the lipid kinase PI3Kδ, was evaluated in 54 patients with relapsed/refractory chronic lymphocytic leukemia (CLL) with adverse characteristics including bulky lymphadenopathy (80%), extensive prior therapy (median 5 [range 2-14] prior regimens), treatment-refractory disease (70%), unmutated IGHV (91%), and del17p and/or TP53 mutations (24%). Patients were treated at 6 dose levels of oral idelalisib (range 50-350 mg once or twice daily) and remained on continuous therapy while deriving clinical benefit. Idelalisib-mediated inhibition of PI3Kδ led to abrogation of Akt phosphorylation in patient CLL cells and significantly reduced serum levels of CLL-related chemokines. The most commonly observed grade ≥3 adverse events were pneumonia (20%), neutropenic fever (11%), and diarrhea (6%). Idelalisib treatment resulted in nodal responses in 81% of patients. The overall response rate was 72%, with 39% of patients meeting the criteria for partial response per IWCLL 2008 and 33% meeting the recently updated criteria of PR with treatment-induced lymphocytosis.(1,2) The median progression-free survival for all patients was 15.8 months. This study demonstrates the clinical utility of inhibiting the PI3Kδ pathway with idelalisib. Our findings support the further development of idelalisib in patients with CLL. These trials were registered at clinicaltrials.gov as #NCT00710528 and #NCT01090414.

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          Author and article information

          Journal
          Blood
          Blood
          1528-0020
          0006-4971
          May 29 2014
          : 123
          : 22
          Affiliations
          [1 ] Dana Farber Cancer Institute, Boston, MA;
          [2 ] The Ohio State University, Columbus, OH;
          [3 ] Stanford University, Stanford, CA;
          [4 ] Sarah Cannon Research Institute, Nashville, TN;
          [5 ] Washington University, St. Louis, MO;
          [6 ] Oregon Health & Sciences University, Portland, OR;
          [7 ] University of Wisconsin, Madison, WI;
          [8 ] Moffitt Cancer Center and.
          [9 ] Gilead Sciences, Inc., Seattle, WA; and.
          [10 ] Weill Cornell Medical College, New York, NY.
          Article
          blood-2013-11-535047
          10.1182/blood-2013-11-535047
          24615777
          c7330eca-c96f-4135-9a31-52f2c2521b5b
          © 2014 by The American Society of Hematology.
          History

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