Consultant Mayo clinic, Division of Hematology Rochester, Minnesota, United States
Introduction: Highly effective therapies in multiple myeloma (MM), highlights the need for more sensitive biomarkers for response and progression assessments. Serum-free light chain (s-FLC) has a high specificity /sensitivity for detecting monoclonal paraprotein. The difference between Involved and uninvolved FLC (d-FLC) is used by the International Myeloma Working Group (IMWG) for assessing the response/progression in non secretory MM. We attempt to validate if the serial measurement of s-FLC, adds value in monitoring MM with measurable disease.
Methods: This retrospective study included newly diagnosed (MM), evaluated at mayo clinic (Rochester) between 2011-2021. All patients had s-FLC measurable (Involved FLC level ≥ 10 mg/dL, with abnormal ratio) at baseline plus measurable serum and/or urine with serial matched data available. All 3 biomarkers were measured at baseline, after each cycle, and at the time of best response and disease progression. We performed a direct comparison of response categories between 3 markers at each time point.
Results: A total of 841 patients were included, 52% IgMM, 20% light chain (MM) and 28% with measurable M-protein in both serum and urine. After the first cycle of treatment, the major response rates (VGPR, PR) by FLC were (42%,40%), sPEP (11%,47%), and uPEP (51%,17%) (Figure 1). MRRs> 90%, observed earlier by s-FLC (2nd cycle) than by s/u M-protein (4th cycle). Among 81% of patients who achieved ≥VGPR at best response, 90% had response by FLC and urine.In patients with paraprotein response < VGPR, achieving FLC response ≥ VGPR, was associated with better PFS (HR 0.65, P < 0.03). Median d-FLC was reduced by 86% after cycle 1, compared to urine M-protein of 91% (Figure 2). The correlation coefficients between the percentage change of d-FLC and urine M-protein after each cycle, showed a moderate relationship, (r 0.562-0.607,p < .001). A higher degree of correlation was detected in LCCM (r 0.607-0.771,P < .001). After a median follow-up of 51 months, 56% had progression disease (PD): 62% by s-FLC, 56% by serum M-protein and 24% by urine. (Figure 3). Among the 48% of patients with measurable urine M-protein at baseline, 58% developed PD, however only 19.5% had progression by urine M-protein and 68%, presented PD by s-FLC. All patients with PD by urine, had PD by s-FLC. Among 13% (60) of total patients with PD, s-FLC was the only tumor marker detectable.
Conclusions: In this study, a similar response rate between serum FLC and urine paraprotein confirms the current cutoffs used for response categories for s-FLC. Serum FLC changes closely paralleled the changes in measurable urine protein and suggest that 24-hour urine can be replaced by serum FLC for response and progression. With direct comparison, we detected the effect of treatment response earlier with FLC in multiple time points.We also detected in 13% of patients with progression, the serum FLC as the only marker of progression, suggesting value of FLC in monitoring for relapse/progression.
