Constant-Infusion Recombinant Interleukin-2 in Adoptive Immunotherapy of Advanced Cancer

TLDR

Adoptive immunotherapy with bolus recombinant interleukin‑2 can induce tumor regression but causes severe fluid retention and cardiopulmonary stress. The study aimed to maintain efficacy while reducing toxicity by administering escalating doses of rIL‑2 as a constant infusion instead of a bolus. Forty‑eight advanced‑cancer patients received 24‑hour rIL‑2 infusions in five‑day cycles with five‑day rest and leukapheresis, and eight were withdrawn before cell activation. Among 40 evaluable patients, 13 partial and 2 minor responses were observed (32.5 % partial response rate), with responses linked to good performance status, baseline lymphocytes >1400 /µL, and rIL‑2‑induced lymphocytosis ≥6000 /µL; the constant infusion improved safety by reducing fluid‑retention events.

Abstract

Adoptive immunotherapy involving bolus-dose recombinant interleukin-2 (rIL-2) has been reported to induce tumor regression in some patients with cancer, but has been associated with severe fluid retention and cardiopulmonary stress. In an effort to preserve the efficacy but reduce the toxicity of this treatment, we used escalating doses of rIL-2 as a constant infusion rather than as a bolus dose. Forty-eight patients with advanced cancer received rIL-2 as a 24-hour infusion in five-day cycles separated by five-day periods of rest and leukapheresis. Eight patients were removed from the study before receiving cells activated in vitro. In the 40 who could be evaluated for their response, there were 13 partial responses (32.5 percent) and 2 minor responses. Partial responses were observed in Hodgkin's disease (one of one), non-Hodgkin's lymphoma (one of one), lung cancer (one of five), ovarian cancer (one of one), parotid cancer (one of two), renal cancer (three of six), and melanoma (five of ten). Responses were associated with a good performance status, a base-line lymphocyte count above 1400 per cubic millimeter, and an rIL-2-induced lymphocyte count of at least 6000. Optimal lymphocytosis required a priming dose of rIL-2 of 3 X 10(6) U per square meter of body-surface area per day, and 15 of 28 patients receiving this priming dose responded to treatment. A weight gain of more than 10 percent of total body weight (five patients) and dyspnea at rest (six patients) were unusual events restricted to patients with poorer pretreatment performance. We conclude that the administration of rIL-2 as a constant infusion may preserve the antineoplastic activity of adoptive immunotherapy while increasing the safety and comfort of patients.