High-dose rituximab therapy in chronic lymphocytic leukemia.
Rituximab (Rituxan; Genentech, Inc, South San Francisco, CA and IDEC Pharmaceutical Corporation, San Diego, CA) is a chimeric monoclonal antibody that targets mature B cells in most lymphoid B-cell malignancies. Rituximab is approved by the US Food and Drug Administration for therapy for recurrent B-cell lymphoma. In initial clinical trials the activity in small lymphocytic lymphoma, the counterpart of chronic lymphocytic leukemia (CLL), was less than 20%. In an attempt to increase the level of rituximab activity in CLL, we conducted a phase I dose-escalation study to overcome both the lower CD20 antigen density on CLL cells compared with lymphoma cells and the shorter half-life of rituximab in small lymphocytic lymphoma. Cohorts of patients were treated with escalated doses on weeks 2, 3, and 4 after an initial rituximab dose of 375 mg/m2 on day 1. The maximum dose of rituximab evaluated was 2,250 mg/m2. There is clear evidence of a dose-response relationship. Severe toxicity (grades 3 and 4) noted following the first dose of therapy in variant forms of CLL, namely mantle cell lymphoma and prolymphocytic leukemia, was uncommon in typical CLL. No unusual toxicity was noted at higher doses. Further exploration of the dosing schedule of rituximab in CLL and development of combination therapies is necessary. This agent shows promise for interaction in combined chemoimmunotherapy strategies for front-line and relapsed patients with CLL.
Department of Leukemia, The University of Texas M.D. Anderson Cancer Center, Houston 77030, USA.
M
M
Keating
S
S
O'Brien
D000368:Aged; D000911:Antibodies, Monoclonal / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D058846:Antibodies, Monoclonal, Murine-Derived; D018951:Antigens, CD20 / Q000502:physiology; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D002985:Clinical Protocols; D004305:Dose-Response Relationship, Drug; D005260:Female; D006801:Humans; D007945:Leukemia, Lymphoid / Q000188:drug therapy*; D008297:Male; D012008:Recurrence; D000069283:Rituximab
D000911:Antibodies, Monoclonal; D058846:Antibodies, Monoclonal, Murine-Derived; D018951:Antigens, CD20; D000970:Antineoplastic Agents; D000069283:Rituximab