Blood Journal
Leading the way in experimental and clinical research in hematology

Results of a phase I study of idelalisib, a PI3Kδ inhibitor, in patients with relapsed or refractory mantle cell lymphoma (MCL)

  1. Brad S. Kahl1,*,
  2. Stephen E. Spurgeon2,
  3. Richard R. Furman3,
  4. Ian W. Flinn4,
  5. Steven E. Coutre5,
  6. Jennifer R. Brown6,
  7. Don M. Benson7,
  8. John C. Byrd7,
  9. Sissy Peterman8,
  10. Yoonjin Cho8,
  11. Albert Yu8,
  12. Wayne R. Godfrey8, and
  13. Nina D. Wagner-Johnston9
  1. 1 University of Wisconsin Carbone Cancer Center, Madison, WI, United States;
  2. 2 Oregon Health and Sciences University, Portland, OR, United States;
  3. 3 Weill Cornell Medical College, New York, NY, United States;
  4. 4 Sarah Cannon Research Institute, Nashville, TN, United States;
  5. 5 Stanford University Medical Center, Stanford, CA, United States;
  6. 6 Dana-Farber Cancer Institute, Boston, MA, United States;
  7. 7 The Ohio State University, Columbus, OH, United States;
  8. 8 Gilead Sciences, Seattle, WA, United States;
  9. 9 Washington University School of Medicine, St. Louis, MO, United States
  1. * Corresponding author; email: bsk{at}

Key points

  • This clinical study assessed idelalisib, a selective PI3Kδ inhibitor, in 40 patients with relapsed/refractory mantle cell lymphoma (MCL)

  • In a dose-escalation trial with heavily pretreated patients an overall response rate of 40% was observed with an acceptable safety profile


Idelalisib, an oral inhibitor of PI3Kδ, was evaluated in a 48-week phase I study (50-350 mg qd or bid) enrolling 40 patients with relapsed/refractory mantle cell lymphoma (MCL). Primary outcome was safety and dose-limiting toxicity (DLT). Secondary outcomes were pharmacokinetic parameters, pharmacodynamic effects, overall response rate (ORR), progression-free survival (PFS), and duration of response (DOR). Patients without DLT and no evidence of disease progression after 48 weeks enrolled in the extension study. Patients had median age of 69 years (52-83) and received median of 4 prior therapies (1-14); 17/40 (43%) were refractory to their most recent treatment. Median duration of idelalisib treatment was 3.5 months (range, 0.7-30.7), with 6 (15%) continuing extension treatment. Common grade ≥3 adverse events (AEs) included (total%/grade ≥3%) diarrhea (40/18), nausea (33/5), pyrexia (28/0), fatigue (25/3), rash (23/3), decreased appetite (20/15), upper respiratory infection (20/0), pneumonia (13/10), and ALT or AST elevations (60/20). Nine (25%) patients discontinued therapy due to AEs. ORR was 16/40 (40%), with CR in 2/40 (5%) patients. Median DOR was 2.7 months, median PFS was 3.7 months, and 1-year PFS was 22%. These data provide proof of concept that targeting PI3Kδ is a viable strategy and worthy of additional study in MCL. This study is registered at, identifier: NCT00710528.

  • Submitted November 8, 2013.
  • Accepted January 21, 2014.