Serum rituximab relationships. (A) The relationship between serum rituximab levels and tumor burden. The difference in serum rituximab levels between patients with low and high tumor volumes is illustrated. Serum rituximab concentrations were measured throughout the treatment protocol and are plotted for patient 2 (calculated spleen and lymph node volume [CSLV] = 147 mL) and patient 4 (CSLV = 1494 mL). Both patients were administered loading doses of 375 mg/m² rituximab at weeks 0, 1, 2, and 3. Patients with high tumor volumes, as represented by patient 4, saw near-complete clearance of serum rituximab after each loading dose, and their serum rituximab level remained low when the first dosimetric tracer of ¹³¹I-rituximab was administered at week 7. For those with low tumor volumes, however, there was a sequential increase in the peak and trough levels of rituximab throughout the loading process, and serum rituximab concentrations remained significantly elevated in these patients at week 7. ♦ represents patient 2; ■, patient 4; +, administration of unlabeled rituximab (375 mg/m²), * Administration of ¹³¹I-rituximab and unlabeled rituximab (100 mg/m²). (B) The relationship between serum rituximab level and effective half-life of ¹³¹I-rituximab. Serum levels of rituximab were measured at week 7, and low levels correlate with a shorter effective half-life of the first dosimetric tracer of ¹³¹I-rituximab (Spearman rank correlation coefficient = 0.700, P = .009). For patients with serum rituximab levels of less than or equal to 50 μg/mL, the effective half-life of ¹³¹I-rituximab appears to rapidly decline; whereas for patients whose serum level is more than 50 μg/mL, the half-life of the radioimmunoconjuate appears to reach a plateau of approximately 100 to 120 hours.