Clinical Characteristics Analysis of 44 Cases of IgM Multiple Myeloma in China: A Multicenter, Retrospective, Observational Study

Abstract Objective: To analyze the clinical characteristics, treatment response, and prognosis of IgM-type multiple myeloma (MM) in China. Methods: A multicenter, retrospective analysis was conducted on 44 newly diagnosed IgM- type MM patients from 16 MM centers in China between January 2015 to December 2024. Comparative analyses were performed with 618 non- IgM MM patients and 23 cases of Waldenström macroglobulinemia (WM). Results: The mean age of IgM-type MM patients (63.68 years) was significantly older than that of non-IgM MM patients (58.27 years, p=0.003), but younger than WM patients (68.04 years, p=0.043). Compared to non-IgM MM, IgM-type MM patients exhibited higher serum albumin levels, lower β2- microglobulin levels, and a greater proportion of ISS stage I or R- ISS stage I-II disease (all p<0.05). In contrast to WM IgM-type MM patients demonstrated significantly elevated serum creatinine and calcium levels (p=0.008 and p=0.024, respectively). The t(11;14) translocation frequency in IgM-type MM (51.4%, 18/35) markedly exceeded that in non-IgM MM (12.6%, 76/601, p=0.000). WM patients showed significantly higher CD19+ expression by flow cytometry (83.3% vs 10.5%, p=0.006), while CCND1 positivity was more prevalent in IgMtype MM (29.6% vs 0%, p=0.040). No significant differences were observed in complete response (CR) rates (p=0.067) or =very good partial response (=VGPR) rates (p=0.067) between IgM and non-IgM MM following induction chemotherapy. Median progression-free survival (PFS) was 42.18 months for IgM-type MM versus 47.0 months for non-IgM MM (p=0.165), with median overall survival (OS) of 62.79 months and 63.54 months, respectively (p=0.736). Among IgM-type MM patients, those with concurrent t(11;14) translocation and CCND1 positivity demonstrated superior outcomes (median PFS: 101.0 months vs 71.0 months, p=0.378), though statistical significance was limited by sample size. Treatment regimens (PIs, PIs+Imids, or CD38 monoclonal antibodies) showed no significant survival differences (PFS p=0.577; OS p=0.186). Autologous stem cell transplantation (ASCT) in 5 IgM-type MM patients showed promising survival benefits (median PFS: 42.42 months vs NR, p=0.353; OS: 62.80 months vs NR, p=0.141). Conclusion: IgM-type MM presents with older onset, earlier-stage disease by ISS or R-ISS criteria, and high t(11;14) incidence, yet demonstrates comparable prognosis to non-IgM- type MM. ASCT may significantly improve survival. Distinctive features including bone marrow morphology, flow cytometry profiles, cytogenetics, and MYD88 mutation status facilitate differentiation from WM. This study provides foundational evidence for understanding the clinicopathological and cytogenetic characteristics of Chinese IgM MM patients. Keywords: IgM-type multiple myeloma; Clinical characteristics; t(11;14) translocation; Prognosis