Interleukin-2 in therapy of hematologic malignancies.

T HE ARTICLE BY Gisselbrecht et all in this issue of Blood describes the activity of single-agent interleukin-2 (IL-2) in a heterogeneous group of previously treated patients with malignant non-Hodgkin’s lymphoma (NHL), Hodgkin’s disease, and cutaneous T-cell lymphoma (CTCL). The number of patients within each of the defined groups is relatively small, and the confidence intervals surrounding the observed response rates are correspondingly quite large. Nevertheless, the investigators are to be congratulated for accumulating this clinical experience and documenting the activity of single-agent IL-2 in these malignancies. Conducting phase I1 trials of a biologic agent in advanced lymphoma populations has proven exceedingly difficult, particularly when the agent, like IL-2, has substantial acute toxicity and requires inpatient administration. Several phase I1 trials of IL-2 alone or in combination with other agents were sponsored by the Cancer Therapy Evaluation Program of the National Cancer Institute (NCI) in both single institutions and major cooperative groups; with rare exception, most did not meet accrual goals and were closed prematurely. The reasons for this difficulty, although not entirely clear, are undoubtedly related to the relative sensitivity, even in relapsed patients and however transiently, of these neoplasms to chemotherapy. Furthermore, there is an understandable bias of investigators and practitioners to place these patients on second-line chemotherapy regimens or to proceed to highdose chemotherapy with marrow transplantation, along with a reluctance to expose patients to agents that are unlikely to have a direct antitumor effect. These practices leave only a small population of patients that can meet the strict performance status and organ function eligibility criteria common to IL-2 protocols. Reviews combining the results of several small studies of IL-2 alone or in combination with adoptively transferred lymphokine-activated killer (LAK) cells in patients with malignant lymphoma (including some patients reported in Gisselbrecht et all) were recently p~bl i shed .~ .~ Using this expanded database, one can conclude that IL-2 has low-level antitumor activity against follicular and diffuse NHL, and has some activity in Hodgkin’s disease. Activity has also been observed in patients with CTCL, but the numbers of patients treated have been too small to accurately determine a response rate. In general, the duration of most of the responses in all of these indications has been brief and the clinical significance marginal. However, a few patients (gen-