Consolidation of first remission with (90)Y-ibritumomab tiuxetan in advanced-stage follicular lymphoma is highly effective with no unexpected toxicities, prolonging PFS by 2 years and resulting in high PR-to-CR conversion rates regardless of type of first-line induction treatment.

AimsTo characterize alemtuzumab pharmacokinetics and its exposure-response relationship with white blood cell (WBC) count in patients with B-cell chronic lymphocytic leukaemia (CLL). MethodsNonlinear mixed effects models were used to characterize plasma concentration-time data and WBC count-time data from 67 patients. Logistic regression was used to relate summary measures of drug exposure to tumour response. ResultsAlemtuzumab pharmacokinetics were best characterized by a two-compartment model with nonlinear elimination where Vmax (mg h -1 ) was [1020 ¥ (WBC count/10 ¥ 10 9 l -1 ) 0.194 ], Km was 338 mg l -1 , V1 was 11.3 l, Q was 1.05 l h -1 and V2 was 41.5 l. Intersubject variability (ISV) in Vmax, Km, V1 and V2 was 32%, 145%, 84% and 179%, respectively. The reduction in WBC over time was modelled by a stimulatory loss indirect response model with values of 18.2 for Emax, 306 mg l -1 for EC50, 1.56 ¥ 10 9 cells l -1 h -1 for Kin and 0.029 per h for Kout. The probability of achieving a complete or partial response was Ն50% when the maximal trough concentration exceeded 13.2 mg ml -1 or when AUC0-t exceeded 484 mg h -1 ml -1 . ConclusionsAlemtuzumab displayed time-and concentration-dependent pharmacokinetics with large interpatient variability, both in pharmacokinetics and pharmacodynamics, which was probably reflective of differences in tumour burden among patients. A direct relationship between maximal trough concentrations and clinical outcomes was observed, with increasing alemtuzumab exposure resulting in a greater probability of positive tumour response.

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