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.

Figure 1

Nodal response to treatment with idelalisib and rituximab by patient, in primary study. Best nodal response for 50 patients evaluable for lymph node response (14 inevaluable: 12 from lack of baseline adenopathy and 2 from discontinuation before 8 weeks) (black bars) and patients with either del(17p) or TP53 mutations (N = 5; 4 inevaluable patients not shown) (gray bars). Response assessed by physical examination or CT scan according to standard criteria. SPD, sum of the products of the perpendicular diameters of measured lymph nodes.

Figure 2

Improvement in median (Q1, Q3) hematologic parameters (A) and lymphocyte counts (B) over time, in primary study. Squares represent platelet count (n = 17); circles represent hemoglobin (n = 17); triangles represent neutrophils (n = 5). ALC, absolute lymphocyte count; ANC, absolute neutrophil count.

Figure 3

PFS (A) and OS (B) in all patients (thick line, N = 64) and those with either del(17p) or TP53 mutation (thin line, N = 9), in combined primary and extension studies. Median PFS and median OS for both groups have not been reached. PFS, progression-free survival; OS, overall survival.