GOTEBORG, SwedenA postconsolidation regimen of low-dose interleukin-2 (IL-2) and the investigational agent histamine dihydrochloride (Maxamine) appears to increase leukemia-free survival in acute myelogenous leukemia (AML) patients in remission, Bo I. Nilsson, MD, PhD, reported at an ASH poster session.
Therapy with Maxamine, an H2-receptor agonist, is designed to strengthen the effect of cytokines such as IL-2 and interferon-alfa, making it possible to use lower doses of the anticancer agents (see figure for the mechanism of action).
In this phase II trial, 39 AML patients, 26 in first remission and 13 in subsequent remissions, were treated with Maxamine, 0.3 to 0.7 mg SC twice daily injected over 5 to 7 minutes, and IL-2, 1 µg/kg SC twice daily. The drugs were administered in courses of 21 days, followed by 3- to 6-week rest periods, until relapse or complete remission lasting at least 24 months.
At the time of the poster presentation, the investigators (from Sahlgrenska University Hospital, Goteborg; Karolinska Institute, Stockholm; Uppsala University Hospital; and Helsingborg, Sweden) reported that 8,000 self-injections of each drug had been administered at home.
Of 16 evaluable patients, 12 had returned to work during treatment, which was well tolerated and without serious toxicity.
Of the 26 patients in first remission, 15 (58%) remained in complete remission after a median follow-up of 26 months, and median time to relapse had not been reached.
Among the 13 patients in second or subsequent remission at the time of treatment with Maxamine/IL-2, five were still in remission, and median time to relapse was 21 months.
Eight of 11 evaluable patients in second or later remission have achieved remission inversion, meaning the duration of the remission is at least equal to that of the patients own previous remission. In these patients, the second remission duration was 21 months vs 11.8 months for the first remission (P = .04). Remission inversion is important, the researchers said, because subsequent remissions are usually increasingly shorter with current treatments, and only about 10% to 20% of patients normally achieve remission inversion.
Histamine-related side effects included, in some patients, a 5 to 30 mm Hg reduction of systolic blood pressure, mild tachycardia, heat sensation, flushing, and headache, all of which were easily managed and reversible within 30 to 60 minutes, Dr. Nilsson said. The drug also increased gastric acid secretion, which was prevented by the use of omeprazole(Drug information on omeprazole) (Prilosec) during treatment.
The phase II study showed a very encouraging leukemia-free survival, said Dr. Nilsson, clinical development consultant from Helsinborg, Sweden. And the toxicity is very minor with this regimen, which includes fairly low dose IL-2, lower than most other investigators use. However, with this small number of patients, it is clearly not conclusive.
A randomized phase III trial of the regimen in 400 AML patients in first or subsequent remission was ongoing at the time of the ASH meeting.
We have participation from approximately 125 centers in 12 countries on three continents, Kurt R. Gehlsen, PhD, vice president and chief technical officer at Maxim Pharmaceuticals, said in an interview. The treatment period will be 1½ years, so it will take quite some time before we have the final analysis of the data.