A phase 2 study of idelalisib plus rituximab in treatment-naive older patients with chronic lymphocytic leukemia

作者：O'Brien Susan M^*; Lamanna Nicole; Kipps Thomas J; Flinn Ian; Zelenetz Andrew D; Burger Jan A; Keating Michael; Mitra Siddhartha; Holes Leanne; Yu Albert S; Johnson David M; Miller Langdon L; Kim Yeonhee; Dansey Roger D; Dubowy Ronald L; Coutre Steven E

来源：Blood, 2015, 126(25): 2686-2694.

DOI：10.1182/blood-2015-03-630947

Idelalisib is a first-in-class oral inhibitor of PI3K delta that has shown substantial activity in patients with relapsed/refractory chronic lymphocytic leukemia (CLL). To evaluate idelalisib as initial therapy, 64 treatment-naive older patients with CLL or small lymphocytic leukemia (median age, 71 years; range, 65-90) were treated with rituximab 375mg/m(2) weekly x8 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, 0.8-45.81). 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-naive older patients with CLL. These results support the further development of idelalisib as initial treatment of CLL.

• 出版日期2015-12-17