Rituximab is an effective treatment for autoimmune
cytopenias associated with
chronic lymphocytic leukemia. Despite the incorporation of
rituximab into
fludarabine-based
chemotherapy regimens, the incidence of autoimmune
cytopenias has remained high. Inadequate
rituximab exposure due to rapid antibody clearance may be a contributing factor. To test this hypothesis, we measured serum
rituximab levels in patients treated with
fludarabine and
rituximab (375 mg/m(2)). All patients had undetectable
rituximab trough levels by the end of cycle 1, and one-third had undetectable levels already on Day 6 of cycle 1. Although
rituximab trough levels increased progressively with each cycle, only by cycle 4 did the median trough level exceed 10 ug/mL. The median half-life of
rituximab during cycle 1 was 27 hours, compared to 199 hours during cycle 4 (P<0.0001). There was a significant inverse correlation between the
rituximab half-life in cycle 1 and the degree of
tumor burden (P=0.02). Two patients who were identified as having subclinical autoimmune
hemolysis prior to
therapy were given additional doses of
rituximab during the initial cycles of
therapy and did not develop clinically significant
hemolysis. One patient who developed clinically significant
hemolysis during
therapy was given additional
rituximab doses during cycles 3-5 and was able to successfully complete his treatment. In conclusion,
rituximab is cleared so rapidly during the initial cycles of
therapy for
chronic lymphocytic leukemia that most patients have only transient serum levels. More frequent dosing of
rituximab may be required to prevent autoimmune complications in at-risk patients (clinicaltrials.gov identifier:00001586).