Therapeutic drug monitoring of nivolumab in routine clinical practice. A pilot study.

Abstract

A review of the literature about the anti-programmed death1 monoclonal antibody nivolumab permits to verify the existence of severalissues still unresolved about their dosing schedule. The aim of thepresent work was to explore possibilities of nivolumab treatment personalizationthrough therapeutic drug monitoring, in order to improve theireffectiveness and efficiency. Observational, prospective study carried out from May2017 through June 2019 in patients with different tumor diagnoses treatedwith nivolumab. Blood samples were obtained in the routine clinicalpractice, once nivolumab steady state was reached. Serum nivolumablevels were determined by means of quantitative ELISA. The standardschedule of 3 mg/kg every two weeks (Q2W) was modified in somepatients due to different circumstances, and resulting serum concentrationswere compared with those from the non-modified patients and thepublished data. Blood samples from 19 patients in treatment with nivolumabwere analyzed. A total of 39 samples of nivolumab were analyzed between6th and 27th cycles. The standard schedule of 3 mg/kg every twoweeks was modified in 12/19 (60%) patients, with intervals of 3, 4, 5, 6or 7 weeks, once the steady state was reached. No statistically significantdifferences were detected when comparing every two weeks and everyfour week intervals. When the intervals were six or seven weeks, mean plasma concentration showed a statistically significant difference compared with every two weeks. Current data contribute to confirm former suspects aboutthe possibilities of exploring new scenarios to improve and personalizenivolumab dosage. Additional studies to confirm it in bigger series andcorrelate it with clinical results, and to better define the role of therapeuticdrug monitoring in the treatment, are warranted, not only by financialconcerns but also for improving quality of life of patients and clinicalmanagement aspects.