RAPID COMMUNICATION Prolonged Administration of Low-Dose Interleukin-2 in Human Immunodeficiency Virus- Associated Malignancy Results in Selective Expansion of Innate Immune Effectors Without Significant Clinical Toxicity

Ten adult patients with human immunodeficiency virus (HIVJ-associated malignancies (five with lymphoma and five with Kaposi’s Sarcoma) were treated with a daily subcutaneous injection of interleukin-2 (IL-2) for 90 consecutive days in a phase I dose-escalation study. Seven patients had absolute CD4 counts below 200/mm3 at the time malignancy was diagnosed. Each lymphoma patient had obtained a complete or partial remission with standard chemotherapy before initiating IL-2. The daily dose of IL-2 did not change during the 90-day course of therapy. Seventeen courses of IL-2 therapy were completed at doses ranging from 0.4 x lo6 U/m2/d to 1.2 x 10” U/m2/d without significant (grade 111) toxicity. Two of two patients experienced grade 111 toxicity within 21 days of initiating IL-2 at a dose of 1.4 x I O * U/m2/d, but both patients subsequently completed 90 days of therapy a t the maximum tolerated dose (MTD) of 1.2 x 10’ U/mz/d. Although there were no significant increases or decreases in T-cell subsets at any dose level, there was an increase in absolute natural killer INK) cell number at the three highest doses of IL-2 (mean percent increase 247; 95% confidence interval, 124 to 369) that was statistically significant (Wil-