Validation of the dR algorithm using BELLINI clinical trial data
BELLINI was a randomized 2:1, double-blind, multicentre, phase III trial that evaluated venetoclax or placebo in combination with bortezomib and dexamethasone in patients with RRMM [Serum and urine M protein and FLC levels were assessed at baseline and at various time points during the trial (S2 Table in Response assessment was performed by both investigator and IRC in BELLINI, with the IRC assessment used as the ‘gold standard’ when the dR algorithm was applied.The number of responders (defined as having a confirmed PR or better [≥PR]) versus non-responders assigned independently by IRC and by the dR algorithm was compared with Cohen’s Kappa statistic to estimate the level of concordance. To test if the assignment of responders by the dR algorithm could be used to replicate the efficacy conclusions of the BELLINI trial, Cochran-Mantel-Haenszel tests were used to calculate differences in overall response rate between the treatment and placebo arms of the trial, and were stratified based on the number of prior lines of therapy and previous PI treatment.To test the utility of the dR algorithm with incomplete data, gaps were artificially introduced into the BELLINI trial dataset. Missing data were simulated by randomly excluding (i) 50% of all laboratory measurements, and (ii) 50% of serum M protein and FLC assessments and 75% of the available urine M protein measurements. The levels of data reduction were chosen to reflect the availability of laboratory measurements previously observed in RWD [Patients without sufficient laboratory measurements for response assessment according to the dR algorithm criteria were assigned as non-responders to make overall statistical results comparable with the original BELLINI trial results.