Post-Consolidation Immunotherapy with Histamine Dihydrochloride and Interleukin-2 in AML: Long Term Follow-Up of Leukemia-Free Survival and Overall Survival.

Blood - Tập 110 - Trang 1846 - 2007
Mats L. Brune1, Jacob M. Rowe2, Jeff Szer3, Donna E. Hogge4, John Catalano5, Elisabeth Wallhult1, Bo I. Nilsson6, Bengt Simonsson7, Ruth Spearing8, Stephane Allard9, Edward A. Stadtmauer10, Kristoffer Hellstrand1
1University of Goteborg, Sweden
2Dept of Hematology and BMT, Rambam Medical Center, Haifa, Israel
3Dept of Clinical Haematology, Royal Melbourne Hospital, Melbourne, Australia
4B.C. Cancer Research Center, Vancouver, Canada
5Dorevitch Pathology Lab, Frankston, Australia
6Helsingborg, Sweden
7Uppsala University Hospital, Uppsala, Sweden
8Christchurch Hospital, Christchurch, New Zealand
9EpiCept Corp, Tarrytown, NY, USA
10Philadelphia, USA

Tóm tắt

Abstract PURPOSE. To assess the long-term outcome of AML patients (pts) in complete remission (CR) after a phase III study which compared the effect of post-consolidation immunotherapy with interleukin-2 (IL-2) and histamine dihydrochloride (HDC) on leukemia-free survival (LFS) and overall survival (OS). PATIENTS & METHODS. A multi-national, randomized, open-label, phase III study which recruited 261 AML pts in first remission (CR1) and 59 in subsequent remission (CR>1) was conducted between June 1998 and October 2000. Pts were enrolled after after termination of consolidation therapy, stratified by country and CR status, and randomized to either treatment or no treatment (standard of care, control). Forty-one % of pts were >60 yrs (median 57), and 54% were males. Study arms were balanced for known prognostic factors. Two patient populations were studied, i.e. all pts randomized (ITT population; n=320) and pts in CR1. The treatment was self-administered at home and included ten 3-week courses of low-dose IL-2 (aldesleukin, Chiron Corp) 18 000 U/kg sc bid, plus HDC (EpiCept) 0.5 mg sc bid. Cycles 1–3 comprised 3 wks of treatment and 3 wks of rest, whereas in cycles 4–10 the rest periods were 6 wks. As reported previously (Blood2006; 108:88), the trial met the primary endpoint of prolonged leukemia-free survival (LFS) for all pts randomized (p=0.008 in favor of the treatment arm) at a median of 46 months of follow-up. The present long-term assessment of efficacy was conducted in August 2006, 30 months after the lock of the original data base. RESULTS. Follow-up forms were retrieved from 86% (n=107; 59 HDC/IL-2 recipients, 48 no treatment,) of the 124 pts pts who were alive at original study cut-off. In the long-term analysis, median LFS in the ITT population was 11 and 8.8 months in HDC/IL-2 and no treatment groups, respectively. In the CR1 population, median LFS was 15 and 9.7 months in HDC/IL-2 and no treatment groups, respectively. The benefit of treatment both for the ITT population (p=0.017) and in CR1 pts (p=0.026) was demonstrated by log-rank testing. Kaplan-Meier (KM) estimates for LFS at 60 months revealed a trend in favor of the treatment group in the ITT population (29.6 vs 20.6%; p=0.065) and a significant difference in the CR1 population (34.4 vs 21.7%, p=0.024). The median OS of CR 1 pts were 44 months (HDC/IL-2) and 28 months (no treatment), but the difference did not attain statistical significance (log rank test: p=0.22; KM estimate at 60 months: p=0.07). CONCLUSION. Post-consolidation immunotherapy with HDC/IL-2 results in significant long-term improvement of LFS.

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Blood

Tập 110

1846

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