Correlation between lymphocyte counts and response to outpatient intravenous interleukin-2 preceded by famotidine in metastatic melanoma.

Abstract

8585 Background: Increased numbers of peripheral blood lymphocytes have been seen in patients receiving high-dose continuous and bolus infusion Interleukin-2 (IL-2) regimens. The toxicity of high-dose IL-2 due to a “capillary leak” syndrome requires in-patient administration of such regimens. Daily intravenous doses of IL-2 of 18-21.6 MIU/m2 over 15-30 minutes have been developed to attempt to lessen toxicity of this therapy. Famotidine may increase Interleukin-2 internalization by the IL-2 receptor on lymphocytes (Tsunoda, 1992). Previously, we have shown that patients with metastatic melanoma may be treated safely with outpatient intravenous Interleukin-2 preceded by intravenous famotidine daily for 3-5 days (Quan et al, 2003; Quan et al, 2010). The current study involves 17 patients with metastatic melanoma. Methods: Thirteen patients with stage IV melanoma received IL-2 18 MIU/m2 intravenously (IV) preceded by famotidine 20 mg IV daily for 3 days for six consecutive weeks. Four patients with metastatic melanoma received IL-2 21.6 MIU/m2 IV preceded by famotidine 20 mg IV daily for four days every 3 weeks. Peripheral blood lymphocyte counts were measured on the first day of each week of IL-2 therapy for all patients. Student’s t-test was used to compare the highest lymphocyte counts in responding patients vs. non-responders. Results: Four patients experienced either a complete (2) or partial (2) response. Thirteen patients were non-responders. The median lymphocyte count achieved in the responding patients was 4750/mm3 (range: 3100-5314/mm3) compared to the median of 2400/mm3 (range: 1500-4949/mm3) in the non-responders (p = 0.008). Conclusions: Peripheral blood lymphocyte numbers are significantly higher in patients with metastatic melanoma responding to outpatient intravenous Interleukin-2 preceded by famotidine than in non-responders. Further studies using flow cytometry and lymphocyte cytoxicity assays are currently being done.