CHICAGO – When paired with rituximab, the experimental agent idelalisib was associated with durable progression-free survival rates in older patients with treatment-naive chronic lymphocytic leukemia or small lymphocytic lymphoma, Dr. Susan M. O’Brien reported at the annual meeting of the American Society of Clinical Oncology.
Among 64 patients in an open-label phase II study, the overall response rate was 97%, consisting of 19% complete responses and 78% partial responses. Among 9 patients with chromosome 17 abnormalities, which are associated with a poor prognosis, 3 had a complete response and 6 had a partial response, said Dr. O’Brien, of the University of Texas MD Anderson Cancer Center in Houston.
Dr. Susan O'Brien
Progression-free survival (PFS) at 24 months was 93% among all patients, and 100% among the 9 patients with the poor-prognosis TP53 mutation or a deletion in chromosome 17 (17p).
"I think that these data, particularly the PFS, really support further evaluation of this agent in front-line CLL [chronic lymphocytic leukemia]," she said.
Idelalisib (GS-1101) is a targeted, highly selective oral inhibitor of the P13 kinase delta isoform (P13K-delta). The oral drug inhibits proliferation of many B-cell malignancies and induces apoptosis, and it inhibits homing and retention of malignant B cells in lymphoid tissues, Dr. O’Brien explained.
In a phase I trial also reported at this year’s ASCO meeting, 72% of 54 patients with relapsed/refractory CLL treated with single agent idelalisib had a partial response, with a 1-month median time to response and a response duration of 16-plus months, reported Dr. Jennifer R. Brown, director of the Chronic Lymphocytic Leukemia Center at the Dana-Farber Cancer Institute in Boston.
In the phase II study conducted by Dr. O’Brien, patients aged 65 years and older with previously untreated CLL were given idelalisib 150 mg twice daily for 48 weeks and rituximab 375 mg/m2 once weekly for 8 weeks. Disease status was determined by investigators. Those patients who did not have disease progression after 48 weeks were allowed to stay on therapy in an extension study.
In the primary study, 62 of 64 patients completed the 8 weeks of therapy with rituximab and idelalisib, and 43 completed all 48 weeks. Of the 21 who discontinued therapy, 17 did so because of adverse events, 3 died, and 1 withdrew consent. Of 40 patients enrolled in the extension phase of the trial, 33 were still on study as of May 2013. Of the 7 patients who withdrew from the extension study, 6 did so because of adverse events and 1 withdrew consent.
Of the 64 patients started on the drug combination in the primary study, 12 had a complete response, and 3 of these patients had a 17p deletion and/or TP53 mutation. Partial responses occurred in 50 patients, 6 of whom had mutations or deletions.
In all, 23% of patients in the primary and extension studies had grade 3 diarrhea and/or colitis. Grade 3 or greater pneumonia occurred in 17%, transaminase elevations in 23%, and neutropenia in 28%. Of the patients who discontinued therapy due to adverse events, 5 did so because of respiratory events in the first 24 weeks, and 5 did so because of diarrhea/colitis during the extension study. Other causes of discontinuation were anemia and elevated transaminases.
The study was sponsored by Gilead Sciences. Dr. O’Brien disclosed receiving research funding from the company. Dr. Brown reported having no relevant financial disclosures.