Population Pharmacokinetics, Efficacy, and Safety of Moxetumomab Pasudotox in Patients With Relapsed or Refractory Hairy Cell Leukemia.

Aims To characterize the pharmacokinetics (PK) of moxetumomab pasudotox, an anti-CD22 recombinant immunotoxin, in adults with relapsed or refractory hairy cell leukaemia, we examined data from a phase 1 study (Study 1001;n= 49) and from the pivotal clinical study (Study 1053;n= 74). Methods Data from both studies were pooled (n= 123) to develop a population PK model. Covariates included demographics, disease state, liver and kidney function, prior treatment, and antidrug antibodies (ADAs). Exposure-response and exposure-safety were analysed separately by study. A 1-compartment model with linear elimination from the central compartment and 2 clearance (CL) rates was developed. Results Moxetumomab pasudotox was cleared more rapidly after cycle 1, day 1 (CL1= 24.7 L/h) than subsequently (CL2= 3.76 L/h), with high interindividual variability (116 and 109%, respectively). In Study 1053, patients with ADA titres >10 240 showed ~4-fold increase in CL. Higher exposures (>= median) were related to higher response rates, capillary leak syndrome and increased creatinine (Study 1053 only), or grade >= 3 adverse events (Study 1001 only). Clinical benefits were still observed in patients with lower exposure or high ADA titres. Conclusion Despite a high incidence of immunogenicity with increased clearance, moxetumomab pasudotox demonstrated efficacy in hairy cell leukaemia.