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

Jennifer R. Brown, John C. Byrd, Steven E. Coutre, Don M. Benson, Ian W. Flinn, Nina D. Wagner-Johnston, Stephen E. Spurgeon, Brad S. Kahl, Celeste Bello, Heather K. Webb, Dave M. Johnson, Sissy Peterman, Daniel Li, Thomas M. Jahn, Brian J. Lannutti, Roger G. Ulrich, Albert S. Yu, Langdon L. Miller and Richard R. Furman

Key points

  • Idelalisib was evaluated in 54 patients with heavily pretreated chronic lymphocytic leukemia, and target inhibition was documented in vivo.

  • Oral idelalisib therapy demonstrated a favorable safety profile and rapidly induced durable disease control in the majority of patients.


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 CLL and multiple 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 mutation (24%). Patients were treated at 6 dose levels of oral idelalisib, ranging from 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 chemo- and cytokines. 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 ORR 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. The median PFS for all patients was 15.8 months; the median OS was not reached. 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 studies are registered at, Identifiers: NCT00710528 and NCT01090414.

  • Submitted November 1, 2013.
  • Accepted January 29, 2014.