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

Abstract

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 (AEs) occurring in 20% or more patients (total%/grade ≥3%) included diarrhea (36/8), fatigue (36/3), nausea (25/3), rash (25/3), pyrexia (20/3), and 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 trials were registered at clinicaltrials.gov as NCT00710528 and NCT01090414.

• Authors: Ian W Flinn, Brad S Kahl, John P Leonard, Richard R Furman, Jennifer R Brown, John C Byrd, Nina D Wagner-Johnston, Steve 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, Stephen E Spurgeon
• Journal: Blood (Blood) Vol. 123 Issue 22 Pg. 3406-13 (May 29 2014) ISSN: 1528-0020 [Electronic] United States
• PMID: 24615776 (Publication Type: Clinical Trial, Phase I, Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: © 2014 by The American Society of Hematology.

Chemical References

• Antineoplastic Agents
• Phosphoinositide-3 Kinase Inhibitors
• Purines
• Quinazolinones
• idelalisib

Topics

• Adult
• Aged
• Aged, 80 and over
• Antineoplastic Agents (administration & dosage, adverse effects, pharmacokinetics, therapeutic use)
• Female
• Humans
• Lymphoma, Non-Hodgkin (diagnosis, drug therapy, mortality)
• Male
• Middle Aged
• Neoplasm Grading
• Phosphoinositide-3 Kinase Inhibitors
• Purines (administration & dosage, adverse effects, pharmacokinetics, therapeutic use)
• Quinazolinones (administration & dosage, adverse effects, pharmacokinetics, therapeutic use)
• Salvage Therapy
• Treatment Outcome