MGUS like phenotype in patients with AL amyloidosis: Impact on clinical outcomes for patients treated with bortezomib-containing regimens (BCR).

Abstract Multiple Myeloma and Light-chain (AL) amyloidosis are clonal plasma cell disorders with different clinical expressions. Recently, Burgos L et al. described an algorithm to classify patients with Monoclonal Gammopathy of Clinical Significance (MGUS)-like phenotype that was developed based on two flow cytometry parameters as well as revised ISS stage, transplant eligibility and depth of response. In our analysis, we used the European modification of the Mayo staging system for AL amyloidosis that refines the original Mayo staging by incorporating NT-proBNP levels for further risk stratification within stage III patients and as such this system was used instead of the revised stage for our analysis. The calculator is available online (). Methods We performed a retrospective study in patients with new diagnosis of AL amyloidosis treated with Bortezomib-Containing Regimens (BCR) at the Amyloidosis Program of Calgary (APC).An algorithm to identify patients having MGUS-like phenotype was used as reported recently. In the current study, 114 patients treated with BCR from 01/2012 to 04/2025 were evaluated. The primary objective of the study was to assess the impact of MGUS-like phenotype on survival outcomes for patients treated with BCR at the APC.A p value of <0.05 was considered significant. Survival curves were constructed according to the Kaplan-Meier method and compared using the log rank test. Progression-Free Survival (PFS) was defined as the time from treatment to disease progression or death, while overall survival (OS) was defined from the date of treatment to the date of death from any cause. All statistical analyses were performed by using the SPSS 24.0 software. Results A total of 114 patients were evaluated. Median age was 66 years (range 39-88) and 59.6% were male. All patients included in this study received first-line BCR, 50 patients were treated with CyBorD (Cyclophosphamide, Bortezomib and Dexamethasone), 27 with Daratumumab-CyBorD and 36 with CyBorMe (Cyclophosphamide, Bortezomib and Methylprednisolone) with a median of 4 cycles (1-54). In total, 83 (72.8%) and 84 patients (73.7%) had cardiac and renal involvement, respectively. Based on the results obtained from the MGUS-like classifier, 42 patients (36.8%) were described as having MGUS-like phenotype compared to 26 (22.8%) with intermediate phenotype and 46 (40.4%) with MM-like phenotype. VGPR or better was observed in 35/42 (83.3%) compared to 17/26 (65.3%) for the intermediate-like and 22/46 (47%) for the MM-like group, respectively (p=0.002). At the time of analysis, 62 patients (54.4%) are alive and 72 have progressed or died (63.2%). In addition, patients with AL amyloidosis and a MGUS-like phenotype had a better overall survival compared to patients with intermediate or MM-like phenotype (Estimated of 149 months vs Estimated 80.4 and 28.7 months, respectively, p=0.001). Further, Progression-Free survival was longer in the MGUS like phenotype group of patients compared to the intermediate and MM-like groups (72.4 versus 58.2 and 20.9 months, respectively, p=0.003). In a multivariate analysis, MGUS like phenotype, depth of response and less advanced staging correlated with better survival. Summary & Conclusion: We report here the role of MGUS-like phenotype for patients with AL amyloidosis treated with BCR at the Amyloidosis Program of Calgary. Our data validates the effect of MGUS like phenotype on survival in a consecutive treated group of AL amyloidosis cases.