title: A phase 2 study of idelalisib plus rituximab in treatment-naïve older patients with chronic lymphocytic leukemia.
abstract: Idelalisib is a first-in-class oral inhibitor of PI3Kδ that has shown substantial activity in patients with relapsed/refractory chronic lymphocytic leukemia (CLL). To evaluate idelalisib as initial therapy, 64 treatment-naïve older patients with CLL or small lymphocytic leukemia (median age, 71 years; range, 65-90) were treated with rituximab 375 mg/m(2) weekly ×8 and idelalisib 150 mg twice daily continuously for 48 weeks. Patients completing 48 weeks without progression could continue to receive idelalisib on an extension study. The median time on treatment was 22.4 months (range, 0.8-45.8+). The overall response rate (ORR) was 97%, including 19% complete responses. The ORR was 100% in patients with del(17p)/TP53 mutations and 97% in those with unmutated IGHV. Progression-free survival was 83% at 36 months. The most frequent (>30%) adverse events (any grade) were diarrhea (including colitis) (64%), rash (58%), pyrexia (42%), nausea (38%), chills (36%), cough (33%), and fatigue (31%). Elevated alanine transaminase/aspartate transaminase was seen in 67% of patients (23% grade ≥3). The combination of idelalisib and rituximab was highly active, resulting in durable disease control in treatment-naïve older patients with CLL. These results support the further development of idelalisib as initial treatment of CLL. This study is registered at ClinicalTrials.gov as #NCT01203930.
authors.affiliation: University of California-Irvine, Irvine Chao Family Comprehensive Cancer Center, Orange, CA;
authors.forename: Susan M
authors.initials: SM
authors.lastname: O'Brien
authors.affiliation: Columbia University Medical Center, New York, NY;
authors.forename: Nicole
authors.initials: N
authors.lastname: Lamanna
authors.affiliation: University of California-San Diego, San Diego Moores Cancer Center, La Jolla, CA;
authors.forename: Thomas J
authors.initials: TJ
authors.lastname: Kipps
authors.affiliation: Sarah Cannon Research Institute, Nashville, TN;
authors.forename: Ian
authors.initials: I
authors.lastname: Flinn
authors.affiliation: Memorial Sloan-Kettering Cancer Center, New York, NY;
authors.forename: Andrew D
authors.initials: AD
authors.lastname: Zelenetz
authors.affiliation: University of Texas MD Anderson Cancer Center, Houston, TX;
authors.forename: Jan A
authors.initials: JA
authors.lastname: Burger
authors.affiliation: University of Texas MD Anderson Cancer Center, Houston, TX;
authors.forename: Michael
authors.initials: M
authors.lastname: Keating
authors.affiliation: Stanford University School of Medicine, Stanford, CA; and.
authors.forename: Siddhartha
authors.initials: S
authors.lastname: Mitra
authors.affiliation: Gilead Sciences, Foster City, CA.
authors.forename: Leanne
authors.initials: L
authors.lastname: Holes
authors.affiliation: Gilead Sciences, Foster City, CA.
authors.forename: Albert S
authors.initials: AS
authors.lastname: Yu
authors.affiliation: Gilead Sciences, Foster City, CA.
authors.forename: David M
authors.initials: DM
authors.lastname: Johnson
authors.affiliation: Gilead Sciences, Foster City, CA.
authors.forename: Langdon L
authors.initials: LL
authors.lastname: Miller
authors.affiliation: Gilead Sciences, Foster City, CA.
authors.forename: Yeonhee
authors.initials: Y
authors.lastname: Kim
authors.affiliation: Gilead Sciences, Foster City, CA.
authors.forename: Roger D
authors.initials: RD
authors.lastname: Dansey
authors.affiliation: Gilead Sciences, Foster City, CA.
authors.forename: Ronald L
authors.initials: RL
authors.lastname: Dubowy
authors.affiliation: Stanford University School of Medicine, Stanford, CA; and.
authors.forename: Steven E
authors.initials: SE
authors.lastname: Coutre
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage* / Q000009:adverse effects / Q000627:therapeutic use; D018572:Disease-Free Survival; D005260:Female; D006801:Humans; D053208:Kaplan-Meier Estimate; D015451:Leukemia, Lymphocytic, Chronic, B-Cell / Q000188:drug therapy* / Q000401:mortality; D008297:Male; D011687:Purines / Q000008:administration & dosage / Q000009:adverse effects; D052999:Quinazolinones / Q000008:administration & dosage / Q000009:adverse effects; D000069283:Rituximab / Q000008:administration & dosage / Q000009:adverse effects; D016896:Treatment Outcome
chemical_list: D011687:Purines; D052999:Quinazolinones; D000069283:Rituximab; C552946:idelalisib