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 clinicaltrials.gov, Identifiers: NCT00710528 and NCT01090414.
- Submitted November 14, 2013.
- Accepted January 19, 2014.
- Copyright © 2014 American Society of Hematology