Rituximab Using A Thrice Weekly Dosing Schedule in B-Cell Chronic Lymphocytic Leukemia and Small Lymphocytic Lymphoma Demonstrates Clinical Activity and Acceptable Toxicity

Abstract

Rituximab administered thrice weekly for 4 weeks demonstrates clinical efficacy and acceptable toxicity. Initial infusion-related events seem to be cytokine mediated and resolve by the third infusion making rapid administration possible. Future combination studies of rituximab with other therapies in CLL seem warranted.

Therapeutic role of alemtuzumab (Campath-1H) in patients who have failed fludarabine: results of a large international study

“…Other salvage therapies that have been recently tested in refractory B-CLL include the combination of fludarabine and cyclophosphamide, which produced 38% response rates (3% CR) in patients refractory to fludarabine as a single agent, 24 and rituximab, which achieved a 40% response rate (0% CR), in less heavily treated patients than reported in this study. 25,26 This alemtuzumab study shows that patients who had failed treatment with rituximab were still able to respond to alemtuzumab.…”

Addition of rituximab to fludarabine may prolong progression-free survival and overall survival in patients with previously untreated chronic lymphocytic leukemia: an updated retrospective comparative analysis of CALGB 9712 and CALGB 9011

“…While the efficacy of rituximab monotherapy in relapsed CLL is limited, with virtually no complete responses, the finding of similar outcome in the concurrent and sequential treatment arm raises the possibility that attaining an early CR (ie, 2 months after treatment) may not be important to predicting long-term outcome. 8,9,18 As responses to rituximab can often improve following completion of therapy, future studies examining the bone marrow later in treatment will be required to accurately estimate the importance of CR as a surrogate end point to prolonged PFS and OS. All of these limitations mandate caution in overinterpreting the results reported herein beyond strong consideration of fludarabine and rituximab-based combinations in future randomized phase 3 trials.…”

“…Rituximab also has single-agent activity in CLL. [7][8][9] Additionally, several large phase 2 studies combining rituximab with fludarabine 10,11 or the combination of fludarabine and cyclophosphamide 12 have demonstrated a much higher complete response rate than previously observed with any other therapeutic approaches used in CLL before this time. To date, comparative studies of rituximab and fludarabine combinations to fludarabine monotherapy have not been performed.…”

Rituximab therapy in malignant lymphoma

“…A better activity has been observed in untreated patients (Hainsworth et al, 2003). Dose escalation, achieved by a thriceweekly dosing schedule (Byrd et al, 2001), or higher weekly doses, 500-2250 mg/m 2 (O'Brien et al, 2001), is necessary to reach significant clinical activity, with a RR of respectively 45 and 36%, as a single agent. The concurrent administration of rituximab with fludarabine resulted in better results with a RR rate of 90%, with 47% CR (Byrd et al, 2003).…”