No doubt remains: FDA will aprove Ceplene next year, and within a few years EPCT will reach a top earning rate at about $200.000.000 per year in the US. In Europe the Ceplene will be introduced within a month or two.
AuthorBrune, Mats, Sahlgrenska Academy, Gothenburg, Sweden
Co-author(s) Rowe, Jacob M., Rambam Medical Center, Haifa, Israel Buyse, Marc E., International Drug Development Institute, Louvain-la-Neuve, Belgium Squifflet, Pierre, International Drug Development Institute, Louvain-la-Neuve, Belgium Castaigne, Sylvie, Hôpital André Mignot, Le Chesnay, France Allard, Stephane E., EpiCept Corporation, Tarrytown, NY, United States of America Hellstrand, Kristoffer, Sahlgrenska Academy, Gothenburg, Sweden (P)
Topic17. Acute myeloid leukemia – Clinical
KeywordsImmunotherapy, Maintenance, Phase III, Remission
BACKGROUND: A randomized multinational Phase 3 trial in adult AML patients (median age=56.5 years) in complete remission (CR; n=320) treated with histamine dihydrochloride (HDC) in conjunction with low-dose interleukin-2 (IL-2) met its primary endpoint, leukemia-free survival (LFS) at 3 years. A significant benefit on LFS over standard-of-care (controls; no treatment) (P=0.008 and 0.011) was observed in the overall and first remission (CR1) populations, respectively (Brune et al. Blood 2006; 108:88-96). Follow-up to determine long-term patient outcomes has been ongoing (Brune et al. Blood 2007;110:1846a) since the trial ended in 2004. AIM: To assess the durability of the treatment effect on the primary endpoint of LFS and on the secondary endpoint of overall survival (OS) in AML patients after treatment with HDC/IL-2 for up to 10 × 3-week cycles over 18 months compared to controls. METHODS: The randomized study of immunotherapy with HDC/IL-2, aimed at prolonging LFS, included 261 AML patients in CR1 and 59 in subsequent remission (CR>1). Study arms were balanced for all prognostic factors known at the time the study was conducted. HDC and IL-2 doses, both given sc BID, were 0.5 mg and 16,400 U/kg, respectively. In June 2008, 92 months after randomization of the last study patient, follow-up data captured whether patients were alive and still in CR, dates of relapse or death, and causes of death. Between-group differences were evaluated using log-rank tests of Kaplan-Meier estimates stratified by country and CR status. RESULTS: Outcomes data were retrieved for 88% of 124 patients (median follow-up 7.4 years) who were alive at the original database lock. At 6 years, 26% of HDC/IL-2-treated patients remain leukemia-free vs. 21% of controls in all patients enrolled. For CR1 patients, 30% of HDC/IL-2-treated vs. 22% of controls remain leukemia-free. This enduring treatment benefit was statistically significant for both the overall and CR1 populations (hazard ratio [HR>=1.41; 95% CI: 1.08 to 1.82; P=0.011 and HR=1.43; 95% CI: 1.07 to 1.91; P=0.015, respectively) (Figure). The trial was not powered to detect a significant benefit in the secondary OS endpoint. However, a trend in OS favoring treatment was noted for both the overall and CR1 populations (HR=1.15; 95% CI: 0.87 to 1.52; P=0.33 and HR=1.18; 95% CI: 0.86 to 1.60; P=0.31, respectively). CONCLUSION: After a minimum of 6 years of follow-up, immunotherapy with HDC/IL-2 in AML patients provides enduring protection from leukemia relapse by maintaining a statistically significant benefit in LFS over no treatment. "