Assessing Osteolytic Lesion Size on Sequential CT Scans Is a Reliable Study Endpoint for Bone Remineralization in Newly Diagnosed Multiple Myeloma

SIMPLE SUMMARY: While MRI is primarily used for vitality analysis in multiple myeloma, the detection of osteolytic manifestations in the mineralized bone is performed on CT scans. For this study based on a homogenous sample of 20 patients with newly diagnosed multiple myeloma, we hypothesized that sequential CT studies can be used to validate remineralization quantitatively and qualitatively as a measure of treatment response. After six cycles of standardized induction therapy with the anti-SLAMF7 antibody elotuzumab in combination with carfilzomib, lenalidomide, and dexamethasone (E-KRd), we were able to record a substantial lesion size decrease associated with the formation of trabecular sclerosis in the majority of responding manifestations. ABSTRACT: Multiple myeloma (MM) frequently induces persisting osteolytic manifestations despite hematologic treatment response. This study aimed to establish a biometrically valid study endpoint for bone remineralization through quantitative and qualitative analyses in sequential CT scans. Twenty patients (seven women, 58 ± 8 years) with newly diagnosed MM received standardized induction therapy comprising the anti-SLAMF7 antibody elotuzumab, carfilzomib, lenalidomide, and dexamethasone (E-KRd). All patients underwent whole-body low-dose CT scans before and after six cycles of E-KRd. Two radiologists independently recorded osteolytic lesion sizes, as well as the presence of cortical destruction, pathologic fractures, rim and trabecular sclerosis. Bland–Altman analyses and Krippendorff’s α were employed to assess inter-reader reliability, which was high for lesion size measurement (standard error 1.2 mm) and all qualitative criteria assessed (α ≥ 0.74). After six cycles of E-KRd induction, osteolytic lesion size decreased by 22% (p < 0.001). While lesion size response did not correlate with the initial lesion size at baseline imaging (Pearson’s r = 0.144), logistic regression analysis revealed that the majority of responding osteolyses exhibited trabecular sclerosis (p < 0.001). The sum of osteolytic lesion sizes on sequential CT scans defines a reliable study endpoint to characterize bone remineralization. Patient level response is strongly associated with the presence of trabecular sclerosis.