Rituximab using a thrice weekly dosing schedule in B-cell chronic lymphocytic leukemia and small lymphocytic lymphoma demonstrates clinical activity and acceptable toxicity

Purpose: Rituximab has been reported to have little activity in small lymphocytic lymphoma (SLL)/chronic lymphocytic leukemia (CLL) and to be associated with significant infusion-related toxicity. This study sought to decrease the initial toxicity and optimize the pharma-cokinetics with an alternative treatment schedule. Patients and Methods: Thirty three patients with SLL/ CLL received dose 1 of rituximab (100 mg) over 4 hours. In cohort I (n 5 3; 250 mg/m2) and cohort II (n 5 7; 375 mg/m2) rituximab was administered on day 3 and there-after three times weekly for 4 weeks using a standard administration schedule. Cohort III (n 5 23; 375 mg/m2) administered rituximab similar to cohort II for the first two treatments and then over 1 hour thereafter. Results: A total of 33 CLL/SLL patients were enrolled; only one patient discontinued therapy because of infusion-related toxicity. Thirteen patients developed transient hy-poxemia, hypotension, or dyspnea that were associated with significant changes in baseline interleukin-6, interleu-kin-8, tumor necrosis factor alpha, and interferon gamma compared with those not experiencing such reactions. Infu-sion-related toxicity occurred more commonly in older (me-dian age 73 v 62 years; P 5.02) patients with no other pretreatment clinical or laboratory features predicting oc-currence of these events. The overall response rate wa