Time‐to‐Event Analysis of Polatuzumab Vedotin‐Induced Peripheral Neuropathy to Assist in the Comparison of Clinical Dosing Regimens

Polatuzumab vedotin, an antibody‐drug conjugate containing monomethyl auristatin E, was associated with an incidence of grade ≥2 peripheral neuropathy (PN) of 55–72% in patients with indolent non‐Hodgkin lymphoma in a phase II study, when dosed 1.8–2.4 mg/kg every 3 weeks until progression or for a maximum of 17 cycles. To quantify the correlation of conjugate exposure and treatment duration with PN risk, a time‐to‐event model was developed using data from phase I and II studies. The model suggested that PN risk increased with conjugate exposure and treatment cycles, and a trend for increased risk with body weight and albumin concentration. When capping the treatment duration to six to eight cycles, the risk ratio of a dose of 2.4 mg/kg vs. 1.8 mg/kg was ≥1.29; the predicted incidence of grade ≥2 PN at 1.8–2.4 mg/kg dose levels was 17.8–37.2%, which is comparable with other antimicrotubule agents for lymphoma treatment.