Results from a phase 2 study ( Study 101-08 ) evaluating Idelalisib ( formerly GS-1101 ), an investigational, targeted, oral inhibitor of PI3K delta, in combination with Rituximab ( MabThera, Rituxan ) for older patients with treatment-naïve chronic lymphocytic leukemia ( CLL ). This regimen achieved a complete response ( CR ) rate of 19% and an overall response rate ( ORR ) of 97%, with estimated progression-free survival ( PFS ) at 24 months of 93%.
Chronic lymphocytic leukemia is a slow-growing cancer that induces the production of too many mature white blood cells. It is the second most common type of leukemia in the United States and can lead to life-threatening complications, including serious infection. Currently, patients with chronic lymphocytic leukemia are usually treated first with Rituximab in combination with one or more chemotherapy agents.
The high overall response rate and durable disease control observed in this phase 2 study suggest that Idelalisib in combination with Rituximab could become an important therapeutic option for CLL patients new to treatment.
Among the 64 patients in the study, Kaplan-Meier estimated proression-free survival ( PFS ) at 24 months was 93%. The median time on treatment was 14 months, with 33 patients remaining on treatment.
The median time to response was two months. No relapses on study have been reported.
The nine patients with chromosome 17p deletion ( del 17p ) ( n=6 ) or mutation in the TP53 gene ( n=3 ), which have been linked to poor prognosis, all responded to therapy including three with a complete response.
Ninety-four percent of patients with thrombocytopenia at baseline responded to treatment ( 16/17 ), as did all patients with anemia at baseline ( 17/17 ).
Of patients with systemic symptoms such as extreme fatigue, fever, night sweats or weight loss ( known as B symptoms ) at baseline, 77% ( 20/26 ) were asymptomatic by eight weeks.
Patients completing 48 weeks of therapy without progression could continue to receive Idelalisib in an extension study. Forty-three patients completed 48 weeks of treatment ( 21 discontinued – 17 due to adverse events, three due to death and one due to other reasons ); 40 patients entered the extension study and 33 remain on treatment.
During the primary and extension study, grade 3 diarrhea and/or colitis was reported in 33% of patients, grade greater than or equal to 3 pneumonia in 17% and grade greater than or equal to 3 transaminase elevations ( measure of liver function ) in 23% of patients.
Study 101-08 is an open-label, single-arm phase 2 trial that enrolled 64 treatment-naïve patients greater than or equal to 65 years old with chronic lymphocytic leukemia or small lymphocytic lymphoma ( SLL ), a less common form of the disease. Patients received intravenous Rituximab 375 mg/m2 weekly for eight weeks and oral Idelalisib 150 mg twice daily for 48 weeks. The primary endpoint of the study is overall response rate, defined as the proportion of patients achieving a complete or partial response with this regimen ( response definitions based on standard criteria ). Patients completing 48 weeks of therapy without progression could continue to receive idelalisib in an extension study.
Idelalisib is a highly selective oral inhibitor of phosphoinositide 3-kinase ( PI3K ) delta, a molecular target that is critical for the activation, proliferation and survival of B lymphocytes. PI3K delta signaling is hyperactive in many B-cell leukemias and lymphomas and drives proliferation, survival and trafficking to lymphoid tissue. Idelalisib is being developed both as a single agent and in combination with approved and investigational therapies. ( Xagena )
Source: Gilead, 2013