ASH: Adding Antisense Agent to Chemotherapy Improves Survival in Relapsed CLL

By Charles Bankhead
ATLANTA, Dec. 11 -- Oblimersen (Genasense) added to chemotherapy produced a significant improvement in long-term survival in patients with relapsed or refractory chronic lymphocytic leukemia compared with chemotherapy alone, researchers said here.
After 54 months of follow-up, survival was 10% with oblimersen versus 2% with chemotherapy alone (P=0.017), Susan O'Brien, M.D., of the University of Texas M. D. Anderson Cancer Center in Houston, told attendees at the American Society of Hematology meeting.
More than twice as many patients treated with oblimersen, which is not yet approved by the FDA, had complete responses, and response duration was more than a year greater compared with chemotherapy alone.
"In a relapsed population, that is excellent survival," said Dr. O'Brien. "The findings also show that response is an appropriate endpoint for these patients because response to therapy is associated with improved survival."
Up-regulation of Bcl-2 is associated with chemotherapy resistance and decreased survival in CLL. Oblimersen is an antisense oligonucleotide that targets Bcl-2 and decreases Bcl-2 protein in a concentration- and time-dependent manner, Dr. O'Brien noted.
Investigators in an international phase III trial compared chemotherapy with fludarabine and cyclophosphamide with oblimersen or without it in 241 patients with relapsed or refractory CLL. All the patients had received at least one prior fludarabine-based chemotherapy regimen. The primary endpoint was the proportion of patients who achieved a complete or partial nodular response.
As reported earlier this year, 17% of oblimersen patients met response criteria compared with 7% of patients treated with chemotherapy alone (J Clin Oncol 2007; 25: 1114-1120). The addition of oblimersen was associated with significant improvement in time to progression and survival.
At ASH, Dr. O'Brien updated the results with follow-up to 54 months. Of the 20 patients who responded to chemotherapy plus oblimersen, 12 (60%) remained alive compared with three of eight (38%) patients in the chemotherapy-only group.
Median duration of response remained significantly prolonged with oblimersen. Estimated at 36 months, median response duration has not been reached in the oblimersen group, whereas median response duration topped out at 22 months in the chemotherapy-only patients (P=0.031).
Three oblimersen patients remain in complete remission, whereas all of the patients treated with chemotherapy alone have progressed or relapsed.
Dr. O'Brien disclosed that she has served as a consultant for and received research support from Genta Inc.
Primary source: American Society of HematologySource reference:O'Brien S, et al "Addition of oblimersen (Bcl-2 antisense) to fludarabine/cyclophosphamide for relapsed/refractory chronic lymphocytic leukemia extends survival in patients who achieve CR/nPR: results from a randomized phase 3 study" Blood 2007; 110(Pt 1 of 2): 231a. Abstract 751.