Population pharmacokinetics (PPK) analyses were conducted to describe the PK characteristics of daratumumab following its administration in combination therapies. Xu and colleagues sought to determine whether different variables influenced the drug’s disposition in patients with multiple myeloma who had received ≥1 prior therapies, and to compare its PK in combination therapies with that of monotherapy.
The PPK analysis of 694 patients included data from phase 3 studies and phase 1/2 studies in which daratumumab was combined with lenalidomide, bortezomib, pomalidomide, thalidomide, and melphalan (all with dexamethasone). Most patients received 16 mg/kg of daratumumab.
Exposure to daratumumab was similar between the monotherapy and combination therapies. Variables factored into the analysis included weight, age, race, gender, ECOG status, lines of prior therapy, type of myeloma, refractory status, treatment regimen, and laboratory measures of renal and hepatic function. Based on combination therapy data, the effects of these numerous intrinsic and extrinsic factors were similar to or smaller than those in the monotherapy studies. None of the investigated intrinsic and extrinsic factors had clinically important effects on the exposure to daratumumab, which remained relatively consistent across the range of body weights.
The current dosing schedule was adequate, over time, to produce concentration levels that maintained target saturation, even when dosed every 4 weeks. Exposure-efficacy analyses suggested that maximum clinical benefit to progression-free survival, duration of response, and overall response rate was attained for the majority of the patients, with an acceptable safety profile, at the recommended dose of 16 mg/kg.
The authors concluded that no dose adjustments are needed, based on any demographic or clinical characteristics, and the 16-mg/kg dosage of daratumumab remains the recommended dose across patient, disease, and treatment variables.
Xu XS, et al. 2016 ASH. Abstract 3340.
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