title: 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.affiliation: Sarah Cannon Research Institute, Nashville, TN;
authors.forename: Ian W
authors.initials: IW
authors.lastname: Flinn
authors.affiliation: University of Wisconsin Carbone Cancer Center, Madison, WI;
authors.forename: Brad S
authors.initials: BS
authors.lastname: Kahl
authors.affiliation: Weill Cornell Medical College, New York, NY;
authors.forename: John P
authors.initials: JP
authors.lastname: Leonard
authors.affiliation: Weill Cornell Medical College, New York, NY;
authors.forename: Richard R
authors.initials: RR
authors.lastname: Furman
authors.affiliation: Dana-Farber Cancer Institute, Boston, MA;
authors.forename: Jennifer R
authors.initials: JR
authors.lastname: Brown
authors.affiliation: The Ohio State University, Columbus, OH;
authors.forename: John C
authors.initials: JC
authors.lastname: Byrd
authors.affiliation: Washington University School of Medicine, St. Louis, MO;
authors.forename: Nina D
authors.initials: ND
authors.lastname: Wagner-Johnston
authors.affiliation: Stanford University Cancer Center, Stanford, CA;
authors.forename: Steve E
authors.initials: SE
authors.lastname: Coutre
authors.affiliation: The Ohio State University, Columbus, OH;
authors.forename: Don M
authors.initials: DM
authors.lastname: Benson
authors.affiliation: Gilead Sciences, Seattle, WA; and.
authors.forename: Sissy
authors.initials: S
authors.lastname: Peterman
authors.affiliation: Gilead Sciences, Seattle, WA; and.
authors.forename: Yoonjin
authors.initials: Y
authors.lastname: Cho
authors.affiliation: Gilead Sciences, Seattle, WA; and.
authors.forename: Heather K
authors.initials: HK
authors.lastname: Webb
authors.affiliation: Gilead Sciences, Seattle, WA; and.
authors.forename: David M
authors.initials: DM
authors.lastname: Johnson
authors.affiliation: Gilead Sciences, Seattle, WA; and.
authors.forename: Albert S
authors.initials: AS
authors.lastname: Yu
authors.affiliation: Gilead Sciences, Seattle, WA; and.
authors.forename: Roger G
authors.initials: RG
authors.lastname: Ulrich
authors.affiliation: Gilead Sciences, Seattle, WA; and.
authors.forename: Wayne R
authors.initials: WR
authors.lastname: Godfrey
authors.affiliation: Gilead Sciences, Seattle, WA; and.
authors.forename: Langdon L
authors.initials: LL
authors.lastname: Miller
authors.affiliation: Oregon Health and Sciences University, Portland, OR.
authors.forename: Stephen E
authors.initials: SE
authors.lastname: Spurgeon
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000009:adverse effects / Q000493:pharmacokinetics / Q000627:therapeutic use*; D005260:Female; D006801:Humans; D008228:Lymphoma, Non-Hodgkin / Q000175:diagnosis / Q000188:drug therapy* / Q000401:mortality; D008297:Male; D008875:Middle Aged; D060787:Neoplasm Grading; D000081082:Phosphoinositide-3 Kinase Inhibitors; D011687:Purines / Q000008:administration & dosage / Q000009:adverse effects / Q000493:pharmacokinetics / Q000627:therapeutic use*; D052999:Quinazolinones / Q000008:administration & dosage / Q000009:adverse effects / Q000493:pharmacokinetics / Q000627:therapeutic use*; D016879:Salvage Therapy; D016896:Treatment Outcome
chemical_list: D000970:Antineoplastic Agents; D000081082:Phosphoinositide-3 Kinase Inhibitors; D011687:Purines; D052999:Quinazolinones; C552946:idelalisib