Journal
LEUKEMIA & LYMPHOMA
Volume 61, Issue 12, Pages 2905-2914Publisher
TAYLOR & FRANCIS LTD
DOI: 10.1080/10428194.2020.1795154
Keywords
Polatuzumab vedotin; relapsed; refractory; diffuse large B-cell lymphoma; pharmacokinetics; exposure-response; dose justification
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Funding
- F. Hoffmann-La Roche Ltd.
- Genentech, Inc.
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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 andC(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.
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