A pilot study of interleukin-2 for adult patients with acute myelogenous leukemia in first complete remission

Abstract

BACKGROUND Interleukin‐2 (IL‐2) has immunomodulatory effects, including stimulating the activity of cytotoxic T cells and natural killer cells, and inducing the generation of lymphokine‐activated killer cells. The authors investigated whether IL‐2 may improve the duration of complete remission (CR) and survival in acute myelogenous leukemia (AML) patients in first CR. METHODS Eighteen patients were included after achieving a CR and receiving at least two courses of consolidation chemotherapy. Therapy was comprised of IL‐2 4.5 × 105 U/m2 daily by continuous infusion (CI) for 12 weeks, plus boluses of 1 × 106 U/m2 on Day 8 and weekly thereafter while continuing the CI. No further chemotherapy was given after the administration of IL‐2 was started. RESULTS The median age of the patients was 50 years (range, 18–73 years), and 7 patients (39%) had an antecedent hematologic disorder (AHD). The median CR duration was 12 months, with 6 patients still alive in CR at a median follow‐up of 64 months (range, 50–82 months). Long term CR by cytogenetics occurred in 2 of 5 patients with a normal karyotype (CR duration of 68+ months and 72+ months, respectively), 1 of 3 patients with t(8;21) (CR duration of 82+ months), 1 patient with inv(16) (CR duration of 67+ months), none of 2 patients with −5/−7 (1 patient died in CR after 10 months), 1 of 2 patients with abnormalities in chromosome 11 (CR duration of 60+ months), and 1 of 4 patients with miscellaneous abnormalities (CR duration of 74+ months). The median survival was 47 months. To assess the significance of these results, the authors selected two historic controls receiving long term postremission chemotherapy per each IL‐2 case. The controls had remained in CR for at least as long as the cases when the latter underwent treatment initiation with IL‐2 and were matched for the number of induction courses required to achieve CR, AHD, cytogenetic abnormalities, and age. Six of 18 IL‐2 patients (33%) were alive in CR at 3 years compared with 7 of 36 controls (19%) (P = 0.31). Nine IL‐2 patients (50%) were alive at 3 years compared with 10 controls (28%) (P = 0.13). CONCLUSIONS These results suggest that IL‐2 is tolerable in AML patients in first CR and should be studied further in future studies as a therapeutic strategy to prolong remission duration. Cancer 1999;85:1506–13. © 1999 American Cancer Society.

Natural killer cell receptors: new biology and insights into the graft-versus-leukemia effect

“…9,[117][118][119][120] In most studies, it has been difficult to convincingly demonstrate a clinical benefit, especially in small phase I and II clinical trials. Although it is not known to what extent cytokines, such as IL-2, may alter the balance between activating and inhibitory receptors on NK cells, it is likely that the inhibitory signals delivered by MHC class I molecules expressed on the autologous target cancer are a major limitation to successful treatment.…”

Interleukin-2 and leukemia

“…Cortes et al 29 6 U/m 2 /day for a median of 9 days over a 59 day period. The 3 year disease-free survival rate was 41%.…”

Role of cytokines in the treatment of acute leukemias: a review

“…[72][73][74][75][76][77] On the basis of the efficacy of IL-2 in these trials, it was hypothesized that the use of IL-2 in first CR might be relatively more beneficial. 78 Cortes et al 78 administered IL-2 4.5 Â 10 5 U/m 2 daily by continuous infusion for 12 weeks, plus boluses of 1 Â 10 6 U/m 2 on day 8 and weekly thereafter to 18 patients with AML in first CR and compared them to historical controls. Although IL-2 administration was feasible and tolerable, no statistically significant improvements in DFS and CR duration was reported.…”

“…Although IL-2 administration was feasible and tolerable, no statistically significant improvements in DFS and CR duration was reported. 78 A study by CALGB examined the tolerability of IL-2 after intensive chemotherapy in 35 elderly patients with AML in first CR. 79 Patients received low-dose IL-2 (1 Â 10 6 IU/m 2 /day subcutaneously for 90 days) or low dose IL-2 with intermittent pulse doses (6-12 Â 10 6 IU/m 2 /day subcutaneously for 3 days) every 14 days for a maximum of five pulses.…”