دورية أكاديمية

Population pharmacokinetics, efficacy, and safety of moxetumomab pasudotox in patients with relapsed or refractory hairy cell leukaemia.

التفاصيل البيبلوغرافية
العنوان: Population pharmacokinetics, efficacy, and safety of moxetumomab pasudotox in patients with relapsed or refractory hairy cell leukaemia.
المؤلفون: Kuruvilla, Denison1 (AUTHOR), Chia, Yen Lin1 (AUTHOR), Balic, Kemal1 (AUTHOR), Yao, Nai Shun2 (AUTHOR), Kreitman, Robert J.3 (AUTHOR), Pastan, Ira3 (AUTHOR), Li, Xia2 (AUTHOR), Standifer, Nathan1 (AUTHOR), Liang, Meina1 (AUTHOR), Tseng, Chih‐Ming1 (AUTHOR), Faggioni, Raffaella1 (AUTHOR), Roskos, Lorin2 (AUTHOR) lorin.roskos@astrazeneca.com
المصدر: British Journal of Clinical Pharmacology. Jul2020, Vol. 86 Issue 7, p1367-1376. 10p. 1 Diagram, 2 Charts, 3 Graphs.
مصطلحات موضوعية: *CAPILLARY leak syndrome, *LEUKEMIA, *MEDICATION safety
مستخلص: 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. [ABSTRACT FROM AUTHOR]
قاعدة البيانات: Academic Search Index
الوصف
تدمد:03065251
DOI:10.1111/bcp.14250