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 objective of this phase 3 study was to determine whether postconsolidation immunotherapy with interleukin-2 (IL-2) and histamine dihydrochloride (HDC) improved the leukemia-free survival (LFS) of adult patients with acute myeloid leukemia (AML) in complete remission (CR). Three hundred twenty patients with AML (median age, 57 years; range, 18-84 years) were stratified by CR1 or subsequent CR (CR > 1) and randomly assigned to treatment with HDC/IL-2 or no treatment (control). Treatment comprised 10 21-day cycles with IL-2 (16 400 U/kg) plus HDC (0.5 mg); both compounds were administered by subcutaneous injection twice daily. Study arms were balanced for age, sex, previous treatment, leukemic karyotypes, time from CR to inclusion, and frequency of secondary leukemia. Three years after enrollment of the last patient, treatment with HDC/IL-2 was found to improve LFS over control in the study population (CR1 + CR > 1, n = 320; P < .01, log-rank test). For patients in CR1 (n = 261), treatment significantly improved LFS (P = .01) with 3-year LFS estimates of 40% (HDC/IL-2) compared with 26% (control). Side effects were typically mild to moderate. These results indicate that HDC/IL-2 treatment offers an efficacious and tolerable treatment for patients with AML in remission.
Brune
Mats
M
Department of Hematology, University of Göteborg, Göteborg, Sweden.
Castaigne
Sylvie
S
Catalano
John
J
Gehlsen
Kurt
K
Ho
Anthony D
AD
Hofmann
Wolf-Karsten
WK
Hogge
Donna E
DE
Nilsson
Bo
B
Or
Reuven
R
Romero
Ana I
AI
Rowe
Jacob M
JM
Simonsson
Bengt
B
Spearing
Ruth
R
Stadtmauer
Edward A
EA
Szer
Jeff
J
Wallhult
Elisabeth
E
Hellstrand
Kristoffer
K
D000208:Acute Disease; D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D018572:Disease-Free Survival; D005260:Female; D006632:Histamine / Q000009:adverse effects / Q000627:therapeutic use*; D006801:Humans; D007167:Immunotherapy; D007376:Interleukin-2 / Q000009:adverse effects / Q000627:therapeutic use*; D007951:Leukemia, Myeloid / Q000628:therapy*; D008297:Male; D008875:Middle Aged; D016016:Proportional Hazards Models; D012008:Recurrence; D012074:Remission Induction; D015996:Survival Rate; D016896:Treatment Outcome
D007376:Interleukin-2; D006632:Histamine