Oblimersen combination improves survival of CLL

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Relapsed chronic lymphocytic leukemia (CLL) patients who had a complete response to combination treatment that included the drug oblimersen survived significantly longer than patients treated with chemotherapy alone, a team led by scientists at The University of Texas M. D. Anderson Cancer Center reports at the 49th Annual Meeting of the American Society of Hematology.

Patients who achieved a complete response with oblimersen have survived so well that a median survival time canstill not be calculated, but it is estimated to exceed 49 months. Those who achieved complete response with chemotherapy alone had a median survival time of 35 months.

"In a relapsed population, that's excellent survival," says lead author Susan O'Brien, M.D., professor in M. D. Anderson's Department of Leukemia. "Survival is linked to achieving complete response".

The Phase III clinical trial compared a regimen of fludarabine and cyclophosphamide (F/C) with F/C plus oblimersen. Known commercially as Genasense(r), oblimersen blocks the Bcl-2 protein, which plays a critical role in progression of chronic lymphocytic leukemia (CLL), including development of resistance to therapy.

By stifling Bcl-2, scientists believe CLL becomes more vulnerable to chemotherapy such as the F/C combination.

In a paper reported in the Journal of Clinical Oncology in March, O'Brien and his colleagues showed that patients who received the oblimersen combination were more likely to have a complete response (20 out of 120 patients, or 17 percent, in comparison to 8 out of 121 patients, 7 percent, who received only the F/C chemotherapy).

Complete response was more durable in the oblimersen-treated patients, with a median duration of at least 36 months compared with 22 months for those on F/C alone.

The question unanswered by the JCO paper was whether this advantage in complete response translated into an advantage in survival, O'Brien says.

Patients were followed for at least three years after randomization or until death or withdrawal from the study. Of the 20 oblimersen-treated patients with a complete response at the end of the first year, 12 survived at least four years. Of the eight complete responders in the other group, four survived at least four years.

The survival data confirm that complete response is a valid endpoint for clinical trials in relapsed or resistant CLL, O'Brien says.


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