Unfortunately, even with the high response rates achieved by rituximab relapse is inevitable. With traditional chemotherapeutic regimens, retreatment using the same or similar agents results in lower response rates, and the duration of those responses gets progressively shorter (Gallagher et al: J Clin Oncol 4:1470-1480, 1986).

Davis et al reported on the initial experience with rituximab retreatment at the 1997 ASH meeting (Blood 90:509a [abstract 2269], 1997). The response rate in 60 patients who had previously responded to rituximab was 40%, including 11% CRs. Perhaps most intriguing was that the duration of initial response and time to progression were 9.8 and 12.4 months, respectively, and that these figures rose to 15+ and 16.7+ months, respectively, with retreatment. At the 1999 ASH meeting, Davis et al (abstract #385) presented the updated, final results of this study. Responses were still ongoing in 6 of 23 patients. All of the patients remained CD20-positive, and none developed a human antichimeric antibody (HACA) reaction.

Igarashi et al (abstract #4384) described data from a multicenter Japanese trial in which patients were initially treated with the standard schedule of rituximab and 59% responded. This study included 14 patients with a variety of histologies in favorable (low, low-intermediate) risk groups (according to the International Prognostic Index [Shipp et al: N Engl J Med 329:987-994, 1993]) who had achieved at least stable disease and then showed evidence of progression. The response rate to rituximab retreatment in this study by Igarashi et al was comparable to the experience of Davis et al, with 36% of patients responding, although the median time to progression was 5 months, compared with 8 months following initial treatment.

Nevertheless, these studies clearly show that rituximab can be used to retreat patients, with a reasonable likelihood of clinical benefit. Moreover, retreatment is not accompanied by the myelosuppression usually associated with repeated courses of chemotherapy. However, patients eventually develop resistance to rituximab, and new approaches are needed.