Exposure-safety and exposure-efficacy analyses of polatuzumab vedotin in patients with relapsed or refractory diffuse large B-cell lymphoma.

Autor: Lu T; Genentech, Inc, South San Francisco, CA, USA., Gibiansky L; QuantPharm LLC, North Potomac, MD, USA., Li X; Genentech, Inc, South San Francisco, CA, USA., Li C; Genentech, Inc, South San Francisco, CA, USA., Shi R; Genentech, Inc, South San Francisco, CA, USA., Agarwal P; Genentech, Inc, South San Francisco, CA, USA., Hirata J; Genentech, Inc, South San Francisco, CA, USA., Miles D; Genentech, Inc, South San Francisco, CA, USA., Chanu P; Genentech, Inc./F. Hoffmann-La Roche Ltd, Lyon, France., Girish S; Genentech, Inc, South San Francisco, CA, USA., Jin JY; Genentech, Inc, South San Francisco, CA, USA., Lu D; Genentech, Inc, South San Francisco, CA, USA.
Jazyk: angličtina
Zdroj: Leukemia & lymphoma [Leuk Lymphoma] 2020 Dec; Vol. 61 (12), pp. 2905-2914. Date of Electronic Publication: 2020 Jul 24.
DOI: 10.1080/10428194.2020.1795154
Abstrakt: Exposure-response relationships were investigated to assess the risk/benefit of polatuzumab vedotin (pola) + bendamustine-rituximab (pola + BR) in relapsed/refractory diffuse large B-cell lymphoma (R/R DLBCL). Analyses were conducted in pivotal study GO29365 (NCT02257567; BR/pola + BR/pola + BG [BG: bendamustine-obinutuzumab]; 1.8 mg/kg pola, every 3 weeks [Q3W], six cycles), and supportive studies DCS4968g (NCT01290549) and GO27834 (NCT01691898) (pola/pola + R/pola + G; 0.1-2.4 mg/kg pola Q3W; eight-cycle landmark), separately. Exposure was characterized as simulated cycle-6 AUC and C max for antibody-conjugated mono-methyl auristatin E (acMMAE) and unconjugated MMAE. Supportive studies showed response rate and safety risk (grade ≥2 peripheral neuropathy; grade ≥3 anemia) increased with exposure, suggesting not to dose below 1.8 mg/kg (up to eight-cycle) for balancing safety and efficacy. Pivotal study with limited exposure range showed no exposure-safety relationship and slightly positive exposure (acMMAE)-efficacy relationship for overall survival. The exposure-response analyses and the observed risk/benefit characteristics in pivotal study supported pola (1.8 mg/kg) +BR Q3W for six cycles in R/R DLBCL patients.
Databáze: MEDLINE
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