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 (
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.
Author notes
Disclosure:Employment: Author SA is presently employed by EpiCept Corp. Consultancy: Authors MB, KH, BN, JR are current or previous consultants to EpiCept Corp. Ownership Interests: Author KH holds patents related to the work described in the abstract. Off Label Use: I will describe a randomized study applying an immunotherapy using two drugs of which one is approved for another indication and one is not approved at all. So, I guess this must be a “discussion of off-label use”?
