Idelalisib, a selective inhibitor of phosphatidylinositol 3-kinase-δ, as therapy for previously treated indolent non-Hodgkin lymphoma

Ian W. Flinn, Brad S. Kahl, John P. Leonard, Richard R. Furman, Jennifer R. Brown, John C. Byrd, Nina D. Wagner-Johnston, Steven E. Coutre, Don M. Benson, Sissy Peterman, Yoonjin Cho, Heather K. Webb, David M. Johnson, Albert S. Yu, Roger G. Ulrich, Wayne R. Godfrey, Langdon L. Miller and Stephen E. Spurgeon

Key points

  • This clinical study assessed idelalisib, a selective PI3Kδ inhibitor, in 64 patients with relapsed indolent non-Hodgkin lymphoma.

  • Idelalisib treatment rapidly induced durable disease responses in heavily pretreated patients with a favorable safety profile.


Idelalisib (GS-1101, CAL-101), an oral inhibitor of phosphatidylinositol 3-kinase-δ, was evaluated in a phase I study in 64 patients with relapsed indolent non-Hodgkin lymphoma (iNHL). Patients had a median (range) age of 64 (32-91) years, 34 (53%) had bulky disease (≥1 lymph nodes ≥5 cm), and 37 (58%) had refractory disease. Patients had received a median (range) of 4 (1-10) prior therapies. Eight dose regimens of idelalisib were evaluated; idelalisib was taken once or twice daily continuously at doses ranging from 50 to 350 mg. After 48 weeks, patients still benefitting (n=19; 30%) enrolled into an extension study. Adverse events occurring in 20% or more patients (AEs, total%/grade ≥3%) included diarrhea (36/8), fatigue (36/3), nausea (25/3), rash (25/3), pyrexia (20/3), chills (20/0). Laboratory abnormalities included neutropenia (44/23), anemia (31/5), thrombocytopenia (25/11), and serum transaminase elevations (48/25). Twelve (19%) patients discontinued therapy due to AEs. Idelalisib induced disease regression in 46/54 (85%) of evaluable patients achieving an overall response rate of 30/64 (47%), with 1 patient having a complete response (1.6%). Median duration of response was 18.4 months, median progression-free survival was 7.6 months. Idelalisib is well tolerated and active in heavily pretreated, relapsed/refractory patients with iNHL. These studies are registered at, Identifiers: NCT00710528 and NCT01090414.

  • Submitted November 14, 2013.
  • Accepted January 19, 2014.