Time-to-Event Analysis of Polatuzumab Vedotin-Induced Peripheral Neuropathy to Assist in the Comparison of Clinical Dosing Regimens.
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Lu D, Gillespie WR, Girish S, Agarwal P, Li C, Hirata J, Chu YW, Kagedal M, Leon L, Maiya V, Jin JY
Time-to-Event Analysis of Polatuzumab Vedotin-Induced Peripheral Neuropathy to Assist in the Comparison of Clinical Dosing Regimens.
CPT Pharmacometrics Syst Pharmacol. 2017 Jun;6(6):401-408. doi: 10.1002/psp4.12192. Epub 2017 May 23.
- PubMed ID
- 28544534 [ View in PubMed]
- Abstract
Polatuzumab vedotin, an antibody-drug conjugate containing monomethyl auristatin E, was associated with an incidence of grade >/=2 peripheral neuropathy (PN) of 55-72% in patients with indolent non-Hodgkin lymphoma in a phase II study, when dosed 1.8-2.4 mg/kg every 3 weeks until progression or for a maximum of 17 cycles. To quantify the correlation of conjugate exposure and treatment duration with PN risk, a time-to-event model was developed using data from phase I and II studies. The model suggested that PN risk increased with conjugate exposure and treatment cycles, and a trend for increased risk with body weight and albumin concentration. When capping the treatment duration to six to eight cycles, the risk ratio of a dose of 2.4 mg/kg vs. 1.8 mg/kg was >/=1.29; the predicted incidence of grade >/=2 PN at 1.8-2.4 mg/kg dose levels was 17.8-37.2%, which is comparable with other antimicrotubule agents for lymphoma treatment.