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 lymph ocytic lymphoma (SLL)/chronic lymphocytic leukemia (CLL) and to be associat ed with significant infusion-related toxicity. This study sought to decreas e the initial toxicity and optimize the pharmocokinetics with an alternativ e 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 = 3; 250 mg/m(2)) and coho rt II (n = 7; 375 mg/m2) rituximab was administered on day 3 and thereafter three times weekly for 4 weeks using a standard administration schedule. C ohort Ill(n = 23; 375 mg/m2) administered rituximab similar to cohort II fo r the first two treatments and then over 1 hour thereafter. Results: A total of 33 CLL/SLL patients were enrolled; only one patient dis continued therapy because of infusion-related toxicity. Thirteen patients d eveloped transient hypoxemia, hypotension, or dyspnea that were associated with significant changes in baseline interleukin-6, interleukin-8, tumor ne crosis factor alpha, and interferon gamma compared with those not experienc ing such reactions. Infusion-related toxicity occurred more commonly in old er (median age 73 v 62 years; P = .02) patients with no other pretreatment clinical or laboratory Features predicting occurrence of these events. The overall response rate was 45% (3% CR, 42% PR; 95% CI 28% to 64%). Median re sponse duration for these 15 patients was 10 months (95% CI, 6.8-13.2; rang e, 3 to 17+). Conclusion: Rituximab administered thrice weekly for 4 weeks demonstrates c linical efficacy and acceptable toxicity. Initial infusion-related events s eem 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. (C) 2001 by American Society of Clinical Oncology.