Ethnic sensitivity assessment: Polatuzumab vedotin pharmacokinetics in Asian and non-Asian patients with previously untreated diffuse large B-cell lymphoma in POLARIX.
Clin Transl Sci
; 16(12): 2744-2755, 2023 12.
Article
en En
| MEDLINE
| ID: mdl-37864313
ABSTRACT
This ethnic sensitivity analysis used data from the phase III POLARIX study (NCT03274492) to assess polatuzumab vedotin pharmacokinetics (PKs) in Asian versus non-Asian patients with previously untreated diffuse large B-cell lymphoma and examined the appropriateness of extrapolating global study findings to Asian patients. PK and population PK (PopPK) analyses assessed polatuzumab vedotin analyte exposures by ethnicity (Asian [n = 84] vs. non-Asian [n = 345] patients) and region (patients enrolled from Asia [n = 80] vs. outside Asia [n = 349]). In patients from Asia versus outside Asia, observed mean antibody-conjugated monomethyl auristatin E (acMMAE) concentrations were comparable (1.2% lower at cycle [C]1 postdose, 4.4% higher at C4 predose; and 6.8% lower at C4 postdose in patients from Asia). Observed mean unconjugated MMAE was lower in patients from Asia by 6.5% (C1 postdose), 20.0% (C4 predose), and 15.3% (C4 postdose). In the PopPK analysis, C6 area under the curve and peak plasma concentrations were also comparable for acMMAE (6.3% and 3.0% lower in Asian vs. non-Asian patients, respectively) and lower for unconjugated MMAE by 19.1% and 16.7%, respectively. By region, C6 mean acMMAE concentrations were similar, and C6 mean unconjugated MMAE concentrations were lower, in patients enrolled from Asia versus outside Asia, by 3.9%-7.0% and 17.3%-19.7%, respectively. In conclusion, polatuzumab vedotin PKs were similar between Asian and non-Asian patients by ethnicity and region, suggesting PKs are not sensitive to Asian ethnicity and dose adjustments are not required in Asian patients to maintain efficacy and safety.
Texto completo:
1
Bases de datos:
MEDLINE
Asunto principal:
Linfoma de Células B Grandes Difuso
/
Inmunoconjugados
Límite:
Humans
País/Región como asunto:
Asia
Idioma:
En
Revista:
Clin Transl Sci
Año:
2023
Tipo del documento:
Article
País de afiliación:
Estados Unidos