MILAN, ItalyGiving interleukin-2 (IL-2, aldesleukin(Drug information on aldesleukin), Proleukin) in combination with the anti-CD20 monoclonal antibody rituximab(Drug information on rituximab) (Rituxan) may increase the antibody’s efficacy in lymphoma patients, apparently because it increases the number of natural killer (NK) cells. Researchers at a Clinical Development Conference sponsored by Chiron Corporation suggested that IL-2 be studied as a regular addition to rituximab therapy and also as an addition to rituxi-mab/chemotherapy regimens.
Joseph Rosenblatt, MD, Pierluigi Porcu, MD, and Maurice Wolin, MD, discussed the rationale for cytokine/rituximab combinations and early clinical trial results at the meeting.
Dr. Rosenblatt, chief of the Division of Hematology/Oncology, University of Miami School of Medicine, said that the strategy of adding IL-2 emerged as a means of further heightening the antibody-dependent cell-mediated cytotoxicity (ADCC) of rituximab.
Rituximab is an anti-CD20 antibody and thus very efficient at removing B cells, but also directly initiates apoptosis by triggering intracellular signaling pathways or by perturbing calcium channels. The antibody also fixes complement. Investigators have been aware for some time that rituximab is associated with a "delayed response" that evolves or increases over time in some patients, and this is assumed to be immune mediated.
Rituximab in Bulky Disease
The need to improve rituximab efficacy is particularly apparent in bulky disease, low-grade non-Hodgkin’s lymphoma (NHL). "Rituximab is a useful drug, but as tumors exceed 5 cm in diameter, the overall response rates decrease, there are partial rather than complete re-sponses, and times to progression are less than satisfactory," Dr. Rosenblatt said. "When rituximab is given alone, a relatively small number of patients have molecular complete remissions, even in the setting of low tumor burden."
Interestingly, about 40% of lymphoma patients who relapse after rituximab respond if treated again, and Dr. Rosenblatt said that the duration of these second responses often exceeds that of the first response, contrary to the result typically seen with chemotherapy.