A phase 2 study of idelalisib plus rituximab in treatment-na¨ ı ve older patients with chronic lymphocytic leukemia

Idelalisib is a first-in-class oral inhibitor of PI3K d that has shown substantial activity in patients with relapsed/refractory chronic lymphocytic leukemia (CLL). To evaluate idelalisib as initial therapy, 64 treatment-na¨ıve older patients with CLL or small lymphocytic leukemia (median age, 71 years; range, 65-90) were treated with rituximab 375mg/m 2 weekly 3 8andidelalisib150mgtwicedailycontinuouslyfor48weeks.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 1 ). 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-na¨ıve 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. ( Blood . 2015;126(25):2686-2694)