Supplementary Material for: Sex-disaggregated analysis of biology, treatment tolerability and outcome of Multiple Myeloma in a German cohort

Introduction: Multiple Myeloma (MM) is a plasma cell disease that affects more men than women. Although there is an obvious imbalance in incidence, knowledge on differences in biology and outcome between the sexes is surprisingly rare.
Methods: We performed a unicentric retrospective analysis of patients with MM treated at a tertiary cancer center between 2003 and 2018.
Results: We present sex-disaggregated analysis of the characteristics and outcome of MM in a cohort of 655 patients (median age at diagnosis 62 years; 363 men with a median age at diagnosis 62 years and 292 women with a median age at diagnosis 63 years, p=0.086). Most patients (n=561, 86%) received myeloma-specific treatment. Median overall survival was 76 months (95% CI 63 – 89) (72 months in men [95% CI 54 – 90] and 83 months in women [95% CI 66 – 100], p=ns). Apart from a higher incidence of moderate and severe anaemia in women (p<0.001) there were no statistically significant differences in the biology of the underlying MM. Similarly, in the group of patients who received high-dose therapy with autologous stem cell transplantation (ASCT, n=313), no statistically significant differences apart from more frequent anaemia in women were detected regarding the biology of the disease. However, there was a trend towards a higher plasma cell infiltration of the bone marrow and towards more frequent high-risk features in women. In contrast, relevant comorbidities were significantly more common in men (for example coronary heart disease in 13% of men vs. 2% of women, p<0.001). Toxicities after ASCT were not significantly different between the sexes with the exception of severe mucositis, which occurred in 22% of men vs. 40% of women (p=0.001).
Conclusion: In conclusion, this first sex-disaggregated analysis of MM patients in Germany supports previous findings that survival is comparable amongst sexes, but women experience more toxicity of high-dose therapy. The higher incidence of clinically relevant anaemia in women warrants further investigation to exclude underlying treatable causes.

引言：多发性骨髓瘤（Multiple Myeloma, MM）是一种浆细胞疾病，男性发病率高于女性。尽管该病的发病率存在显著性别失衡，但目前关于不同性别患者的生物学特征及预后差异的相关研究却极为匮乏，这一点令人意外。
方法：本研究对2003年至2018年间，某三级肿瘤诊疗中心收治的多发性骨髓瘤患者开展了单中心回顾性分析。
结果：本研究对655例患者队列按性别分层分析了多发性骨髓瘤的临床特征与预后情况（诊断时中位年龄为62岁；其中男性363例，诊断时中位年龄62岁，女性292例，诊断时中位年龄63岁，p=0.086）。多数患者（n=561，占比86%）接受了骨髓瘤针对性治疗。所有患者的中位总生存期为76个月（95%置信区间：63~89），其中男性中位总生存期72个月（95%CI：54~90），女性为83个月（95%CI：66~100），组间差异无统计学意义（p=ns）。除女性患者中度及重度贫血的发生率更高（p<0.001）外，多发性骨髓瘤的基础生物学特征未观察到显著性别差异。同样，在接受大剂量化疗联合自体造血干细胞移植（autologous stem cell transplantation, ASCT）的313例患者亚组中，除女性贫血发生率更高外，该病的生物学特征亦未发现显著性别差异。不过，女性患者存在骨髓浆细胞浸润程度更高、高危特征更常见的趋势。与之相反，男性患者的合并症负担显著更高，例如冠心病发生率在男性中为13%，女性仅为2%（p<0.001）。自体造血干细胞移植术后的不良反应总体无显著性别差异，但重度黏膜炎例外：男性发生率为22%，女性为40%（p=0.001）。
结论：综上，这项针对德国多发性骨髓瘤患者的首次按性别分层分析证实，不同性别患者的总生存期相当，但女性患者在接受大剂量治疗时的不良反应更为显著。女性患者临床相关贫血发生率更高这一现象，尚需进一步研究以明确是否存在可干预的潜在病因。