Impact of bone marrow fibrosis in multiple myeloma at diagnosis and on disease course

Introduction: Bone marrow fibrosis (BMF) is found in 8-57% of plasma cell dyscrasias. Increased reticulin in multiple myeloma (MM) is found to be associated with increased plasma cell infiltration and heralds a poorer prognosis. Here we aimed to explore the frequency of BMF at diagnosis and its impact on disease course. Methods: We performed a single-center, retrospective analysis of 217 MM patients with available data who had been evaluated for BMF between January 2010 and June 2022 with a follow-up period of at least 1 year. Univariate and multivariate cox-regression analyses and Kaplan-Meier methods were used in survival analysis. Results: Of 217 patients evaluable for BMF 137 (63%) had detectable BMF while 80 (37%) had no BMF. The median age of the patients was 63 (range: 37 to 89) and females and males accounted for 50.2% (n=109) and 49.8% (n=108), respectively. The median follow-up time was 44 months (range: 12 to 155). Median progression free survival (PFS) in patients with and without BMF was 20 (95% CI: 13-26) and 24 months (95% CI: 11-36) (p=0.286). Median overall survival (OS) in patients with and without BMF was 93 (95% CI: 83-102) and 95 (95% CI: 85-103) months (p=0.346). We evaluated the morphologic paterns of plasma cell distribution and found out that diffuse paterns were more common in BMF (p<0.001). Diffuse plasma cell patern was an independent poor prognostic factor for OS (p<0.023). Mean hemoglobin values in patients without and with BMF were 11.14±2.32 and 10.18±2.23 g/dL, respectively (p=0.003). International Staging System (ISS) stage I patients built 24% (n=33) of patients with BMF while 40% (n=32) of patients without BMF had stage I disease (p=0.047). When we stratified the cohorts with and without fibrosis by two age levels (<65 and ≥65 years), patients ≥65 with BMF had worse OS (p=0.001) and PFS (p=0.007) compared to patients <65 with BMF. OS difference in patients without BMF was not statistically significant (p=0.057) but PFS in patients without BMF was worse in ≥65 patients (p=0.035). In patients with BMF having red blood cell (RBC) transfusion requirements OS (p=0.008) and PFS (p=0.034) were significantly worse than patients without BMF having RBC transfusion requirements. Conclusions: Bone marrow microenvironment is an area of interest. In this study, we could not find any survival difference between patients with and without BMF at diagnosis. Fibrotic MM patients had lower hemoglobin values, higher ISS stages and tendency to have diffuse plasma cell infiltration similar to previous reports. Older age and RBC transfusion need correlated with worsening PFS and OS in patients with BMF while older age had an impact on PFS in nonfibrotic patients. Evaluation of BMF both at diagnosis and following treatment may provide better prognostic significance. Keywords: Multiple Myeloma (MM), Autolog Stem Cell Transplantation (ASCT), Overall Survival (OS), Progression Free Survival (PFS)