key papersKey paper

Improved leukemia-free survival after postconsolidation immunotherapy with histamine dihydrochloride and interleukin-2 in acute myeloid leukemia: results of a randomized phase 3 trial

The primary report of Study 0201: adding histamine dihydrochloride to low-dose interleukin-2 after consolidation improved leukaemia-free survival in acute myeloid leukaemia, with 40 percent against 26 percent leukaemia-free at three years in first remission.

Phase 3 trial whose primary objective was to determine whether postconsolidation immunotherapy with interleukin-2 and histamine dihydrochloride improved leukaemia-free survival of adults with acute myeloid leukaemia in complete remission. Three hundred and twenty patients (median age 57 years, range 18 to 84) were stratified by first or subsequent complete remission and randomly assigned to histamine dihydrochloride plus interleukin-2 or no treatment. Treatment comprised ten 21-day cycles of interleukin-2 (16,400 units per kilogram) plus histamine dihydrochloride (0.5 mg), both by subcutaneous injection twice daily. Arms were balanced for age, sex, previous treatment, karyotype, time from remission to inclusion and secondary leukaemia.

Three years after enrolment of the last patient, treatment improved leukaemia-free survival over control in the study population (n = 320; P < .01, log-rank). For patients in first complete remission (n = 261), treatment significantly improved leukaemia-free survival (P = .01) with 3-year estimates of 40 percent versus 26 percent. Side effects were typically mild to moderate.

Randomised controlled trialChanged practice320 participants

Authors

Brune M, Castaigne S, Catalano J, et al.

Published

Blood, 2006

Full text

doi:10.1182/blood-2005-10-4073 PubMed 16556892

Findings

Leukaemia-free survival improved with histamine dihydrochloride plus interleukin-2 over no treatment in all 320 patients (P < .01, log-rank).
In first complete remission (n = 261), 3-year leukaemia-free survival 40% vs 26% (P = .01).
Side effects typically mild to moderate.

What it means

This is the trial behind the 2008 European authorisation of Ceplene, one of very few maintenance immunotherapies ever approved in acute myeloid leukaemia. The abstract reports no overall survival benefit and the drug is little used today, with oral azacitidine and targeted maintenance filling the space.

Caveats

Open-label, against no treatment rather than placebo.
The 40% vs 26% figure is a first-remission subgroup landmark; the abstract prints no three-year rates for the full population and no hazard ratio.
The registry posts only an estimated enrolment of 360 and no results.