Metabolic activation of tyrosine kinase inhibitors: recent advance and further clinical practice

Yan, Miao; Li, Wenqun; Li, Wenbo; Huang, Qi; Li, Jing; Cai, Hualin; Gong, Hui; Zhang, Bikui; Wang, Yikun

doi:10.1080/03602532.2022.2149775

Cited by 5 publications

(2 citation statements)

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“…This may be the result from different metabolism process and pharmacokinetic characteristics between mAbs and tyrosine kinase inhibitors. Tyrosine kinase inhibitors are usually metabolized by CYP450 enzyme 37 and have short half‐lives, whereas mAbs are mainly metabolized by proteolysis by the liver and the reticuloendothelial system, target‐mediated elimination in lysosomes, and nonspecific endocytosis, which generated the long elimination half‐lives (up to 4 weeks). In literature, the half‐lives for daratumumab 38 are 18–23 days.…”

Section: Discussionmentioning

confidence: 99%

“…This may be the result from different metabolism process and pharmacokinetic characteristics between mAbs and tyrosine kinase inhibitors. Tyrosine kinase inhibitors are usually metabolized by CYP450 enzyme 37 and have short half-lives, whereas mAbs are mainly metabolized by proteolysis by the liver and the reticuloendothelial system, target-mediated elimination Figure 4 TLS associated with mAbs and other anticancer drugs for MM. After excluding some known confounders in sensitivity analysis, we compared the signals of TLS between mAbs and other drugs for MM in a consolidated analysis.…”

Section: Discussionmentioning

confidence: 99%

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Tumor Lysis Syndrome Associated with Monoclonal Antibodies in Patients with Multiple Myeloma: A Pharmacovigilance Study Based on the FAERS Database

Xia

Gong

Zhao

et al. 2023

Clin Pharma and Therapeutics

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Although some tumor lysis syndrome (TLS) cases have been reported with patients with multiple myeloma (MM) taking monoclonal antibodies (mAbs), the association between TLS and mAbs remains mostly unknown. We aim to investigate the association between TLS and mAbs and describe clinical features. We conducted a disproportionality analysis to investigate the link between mAbs and TLS by excluding known confounders and compared with other anticancer drugs. The association between mAbs and TLS was evaluated using information component (IC). Drugdrug interaction signals were calculated based on the Ω shrinkage measure. Parametric distribution with the goodness-of-fit test was used for the reported time-to-onset analysis. From 2016 Q1, to 2022 Q4, a total of 274 TLS with mAbs were reported in the US Food and Drug Administration Adverse Event Reporting System (FAERS) database. There were 27% of patients with TLS with mAbs who died and 20.1% occurred a life-threatening situation. Daratumumab, elotuzumab, and belantamab mafodotin presented a robust disproportionate signal of TLS after excluding known confounders (IC 025 > 0). Daratumumab had the highest disproportionate signal of TLS among all anticancer drugs for MM. Reported time-to-onset analysis showed the median days for TLS with daratumumab, isatuximab, elotuzumab, and belantamab mafodotin were 1.5, 14.5, 5.5, and 5.5 days, respectively. The drugdrug interaction analysis showed the co-administration of drugs known to increase urate, induce hyperkalemia, or hypocalcemia elevated the reporting frequency for TLS with mAbs (Ω 025 > 0). Our postmarketing pharmacovigilance analysis detected the reporting association of TLS and mAbs in patients with MM. Additional studies with robust epidemiological study designs that can validate these findings are warranted.

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Section: Discussionmentioning

confidence: 99%

“…This may be the result from different metabolism process and pharmacokinetic characteristics between mAbs and tyrosine kinase inhibitors. Tyrosine kinase inhibitors are usually metabolized by CYP450 enzyme 37 and have short half-lives, whereas mAbs are mainly metabolized by proteolysis by the liver and the reticuloendothelial system, target-mediated elimination Figure 4 TLS associated with mAbs and other anticancer drugs for MM. After excluding some known confounders in sensitivity analysis, we compared the signals of TLS between mAbs and other drugs for MM in a consolidated analysis.…”

Section: Discussionmentioning

confidence: 99%