Exposure-safety and exposure-efficacy analyses of polatuzumab vedotin in patients with relapsed or refractory diffuse large B-cell lymphoma. Issue 12 (14th October 2020)

• Record Type: Journal Article
• Authors: Lu, Tong; Gibiansky, Leonid; Li, Xiaobin; Li, Chunze; Shi, Rong; Agarwal, Priya; Hirata, Jamie; Miles, Dale; Chanu, Pascal; Girish, Sandhya; Jin, Jin Yan; Lu, Dan
• Is Part Of: Leukemia & lymphoma. Volume 61:Issue 12(2020)
• Page Start: 2905
• Page End: 2914
• Publication Date: 2020-10-14
• Subjects: Polatuzumab vedotin -- relapsed/refractory -- diffuse large B-cell lymphoma -- pharmacokinetics -- exposure-response -- dose justification; Leukemia -- Periodicals; Lymphomas -- Periodicals; 616.99419
• DOI: 10.1080/10428194.2020.1795154
• Languages: English
• ISSNs: 1042-8194

Abstract

Abstract: 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.