Originally published as JCO Early Release 10.1200/JCO.2009.22.5748 on September 8 2009

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5-Year Survival in Patients With Relapsed or Refractory Chronic Lymphocytic Leukemia in a Randomized, Phase III Trial of Fludarabine Plus Cyclophosphamide With or Without Oblimersen

From the University of Texas M. D. Anderson Cancer Center, Houston, TX; Duke University Medical Center, Durham, NC; Yakima Regional Cancer Care Center, Yakima, WA; Cross Cancer Institute, Edmonton, Alberta, Canada; Klinika Hematologii Collegium Medicum Uniwersytetu Jagiellonskiego, Cracow, Poland; Instituto Argentino de Diagnostico y Tratamiento SA, Buenos Aires, Argentina; Roswell Park Cancer Institute, Buffalo; and Long Island Jewish Medical Center, New Hyde Park, NY; Peter MacCallum Cancer Centre and University of Melbourne, Melbourne, Victoria, Australia; Institute of Cancer, Barts and London, London, United Kingdom; and Genta, Berkeley Heights, NJ.

Corresponding author: Susan O'Brien, MD, Division of Hematology, The University of Texas M. D. Anderson Cancer Center, 1515 Holcombe Blvd, Houston, TX 77030; e-mail: sobrien{at}mdanderson.org.

Purpose A randomized trial of oblimersen plus fludarabine/cyclophosphamide (OBL-FC; n = 120) versus FC (n = 121) was conducted in patients with relapsed/refractory chronic lymphocytic leukemia (CLL). The primary end point was met: the complete response (CR) rate, defined as complete or nodular partial response, was significantly greater with OBL-FC than with FC (17% v 7%; P = .025). Among patients with CR, response duration was significantly longer with OBL-FC than with FC (median not reached; > 36 months v 22 months; P = .03). Maximum benefit with OBL-FC, including a four-fold increase in CR rate and a survival benefit with 3 years of follow-up (hazard ratio, 0.53; P = .05), was observed in patients with fludarabine-sensitive disease. We evaluated long-term survival and poststudy CLL therapy among all randomly assigned patients.

Methods Poststudy CLL treatment information was collected. Patients were observed for survival for up to 5 years from the date of random assignment.

Results Poststudy CLL treatment was balanced between arms. Intent-to-treat analysis of 5-year survival showed no significant between-treatment difference (hazard ratio, 0.87; P = .34). Among the greater than 40% of patients with complete or partial remission, a significant 5-year survival benefit was observed with OBL-FC (hazard ratio, 0.60; P = .038). Among patients with fludarabine-sensitive disease who had previously demonstrated maximum benefit with OBL-FC, the previously observed survival benefit improved: a 50% reduction in the risk of death was observed (P = .004).

Conclusion In relapsed/refractory CLL, OBL combined with FC offers patients who achieve complete or partial remission, as well as those who have fludarabine-sensitive disease, a significant survival benefit.

Written on behalf of the Oblimersen CLL Study Group.

Presented in part at the 49th Annual Meeting of the American Society of Hematology, December 8-11, 2007, Atlanta, GA, and at the 44th Annual Meeting of the American Society of Clinical Oncology, May 30-June 3, 2008, Chicago, IL.

Authors' disclosures of potential conflicts of interest and author contributions are found at the end of this article.

Clinical trial information can be found for the following: NCT00024440 [ClinicalTrials.gov] .

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