interleukin-2 (IL-2, aldesleukin, Proleukin) in combination with the anti-CD20
monoclonal antibody 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
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.