Ethnic Sensitivity Assessment: Polatuzumab Vedotin Pharmacokinetics in Asian and Non-Asian Patients with Previously Untreated Diffuse Large B-cell Lymphoma in POLARIX.

This ethnic sensitivity analysis used data from the Phase III POLARIX study (NCT03274492) to assess polatuzumab vedotin pharmacokinetics (PK) in Asian versus non-Asian patients with previously untreated diffuse large B-cell lymphoma (DLBCL) 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] versus non-Asian [n = 345] patients) and region (patients enrolled from Asia [n = 80] versus 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 post-dose, 4.4% higher at C4 pre-dose; and 6.8% lower at C4 post-dose in patients from Asia). Observed mean unconjugated MMAE was lower in patients from Asia by 6.5% (C1 post-dose), 20.0% (C4 pre-dose), and 15.3% (C4 post-dose). In the popPK analysis, C6 area under the curve and peak plasma concentration were also comparable for acMMAE (6.3% and 3.0% lower in Asian versus 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 PK were similar between Asian and non-Asian patients by ethnicity and region, suggesting PK are not sensitive to Asian ethnicity and dose adjustments are not required in Asian patients to maintain efficacy and safety.