Number of responders (≥PR) and non-responders (<PR) in the BELLINI trial as assessed by IRC and the dR algorithm.
dR, derived response; IRC, independent review committee; PR, partial response.In total there were 16 discrepant cases for which different responses were assigned by the IRC and the dR algorithm. In the only case assigned as a non-responder by the dR algorithm but as a PR by the IRC, there were not enough consecutive laboratory test results of the same type to confirm response, although other criteria were met. It is worth noting that the investigator in the BELLINI trial assessed this patient as having minimal response. Of the 15 cases in which the dR algorithm disagreed with the IRC assessment, eight were assigned as responders by investigator’s assessment, showing that there are cases in which the dR algorithm agrees more closely with the investigator’s assessment, and suggesting that these cases could be difficult to assess. The remaining 7/15 cases were assigned as responders by the dR algorithm as they met the criteria for reduction in either serum or urine M protein. It should be noted that agreement between investigator and IRC response assignment in BELLINI reached Cohen’s Kappa of 0.85, suggesting an upper limit to the attainable performance of the dR algorithm.When depths of response were considered separately (i.e. PR, VGPR, CR and sCR) as opposed to grouping as ≥PR, concordance between IRC and the algorithm’s response assignments was lower (Cohen’s Kappa 0.56). This result was expected due to the omission of bone marrow data in the assessment of CR and sCR, which can cause the algorithm to over-assign VGPR as CR/sCR, and CR as sCR (S3 Table in 