Time-to-Event Analysis of Polatuzumab Vedotin-Induced Peripheral Neuropathy to Assist in the Comparison of Clinical Dosing Regimens.
CPT Pharmacometrics Syst Pharmacol
; 6(6): 401-408, 2017 06.
Article
en En
| MEDLINE
| ID: mdl-28544534
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.
Texto completo:
1
Banco de datos:
MEDLINE
Asunto principal:
Enfermedades del Sistema Nervioso Periférico
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Inmunoconjugados
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Modelos Biológicos
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Anticuerpos Monoclonales
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Antineoplásicos
Tipo de estudio:
Clinical_trials
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Prognostic_studies
Límite:
Humans
Idioma:
En
Año:
2017
Tipo del documento:
Article