Interleukin-2 may induce prolonged remissions in advanced acute myelogenous leukemia

Abstract

The administration of interleukin-2 (IL-2) may induce complete remissions in acute myelogenous leukemia (AML) patients with a low proportion of residual bone marrow (BM) blasts. To confirm this preliminary observation, we treated 14 AML patients with advanced disease and with a residual BM blastosis that ranged between 7% and 24% with repeated 5-day cycles of high-dose recombinant IL-2 administered by daily continuous intravenous infusion. Patients who responded have been subsequently submitted to a monthly maintenance scheme with subcutaneous IL-2 at lower doses. While using this schedule and closely monitoring clinical and laboratory conditions, side effects were acceptable and no toxic deaths recorded. Eight of the 14 patients treated with high-dose IL-2 obtained a complete remission (CR). Five remain in persistent CR (four in third CR and one in fourth CR) after a median follow-up time of 32 months (14, 30, 32, 33, and 68 months, respectively). In all five patients, the IL-2-induced remission is the longest in the natural history of the disease. These findings show that IL-2 displays an antileukemic effect in AML with limited residual disease, and suggest that IL-2 should be considered a therapeutic option for resistant or relapsed AML patients.

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

“…Following these results, 14 patients with refractory or relapsed AML with ≤20% BM blasts were treated with a similar schedule. Eight patients (57%) achieved a CR, which was sustained for 14–68 months in 5 patients, but none of the 3 patients refractory to prior chemotherapy responded to IL‐2 16. Other studies also have documented responses in salvage therapy for adult AML 19, 35.…”

“…The schedule of IL‐2 administration has been highly variable among different trials. Some studies used a high dose CI for short periods of time, usually 5 days, repeated after 2–14 days of rest 15, 16, 19, 23. Those studies used doses of 3–18 × 10 6 U/m 2 .…”

“…Those studies used doses of 3–18 × 10 6 U/m 2 . In some of those trials, a maintenance phase followed with IL‐2 administration as a CI 5 days per month 15, 16. Other studies used subcutaneous administration of IL‐2,36, 39 and others used intravenous administration 2 or 3 times per day 35…”

“…These observations prompted the investigation of IL‐2 in patients with AML. Most studies have used IL‐2 in patients with relapsed or refractory AML, or as maintenance for patients in second or later remission,15–19 or after autologous or allogeneic BMT 20–22. However, use of IL‐2 in first CR might be relatively more beneficial, because residual disease might be less, and LAK activity and sensitivity of leukemic cells to LAK‐mediated cytotoxicity might be better 9.…”

Feasibility, toxicity, and biologic response of interleukin-2 after consolidation chemotherapy for acute myelogenous leukemia: a report from the Children's Cancer Group.

“…The hypotheses of no change in median measure between baseline versus postinduction and baseline versus postmaintenance time points were assessed by use of the paired signed-rank test.' 5 Each patient's pretreatment measurement was used as the baseline for the postinduction and the postmaintenance comparison.…”