التفاصيل البيبلوغرافية
| العنوان: |
Population pharmacokinetics, efficacy, and safety of moxetumomab pasudotox in patients with relapsed or refractory hairy cell leukaemia. |
| المؤلفون: |
Kuruvilla, Denison, Chia, Yen Lin, Balic, Kemal, Yao, Nai Shun, Kreitman, Robert J., Pastan, Ira, Li, Xia, Standifer, Nathan, Liang, Meina, Tseng, Chih‐Ming, Faggioni, Raffaella, Roskos, Lorin |
| 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] |
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| قاعدة البيانات: |
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