Infection is the leading cause of death in multiple myeloma (MM). However, the cellular composition associated with immune dysfunction is not defined. We analyzed immune profiles in the peripheral blood of patients with MM (n = 28) and B-cell chronic lymphoproliferative disorders (n = 53) vs. health care practitioners (n = 96), using multidimensional and computational flow cytometry. MM patients displayed altered distribution of most cell types (41/56, 73%), particularly within the B-cell (17/17) and T-cell (20/30) compartments. Using COVID-19 as a case study, we compared the immune response to vaccination based on 64,304 data points generated from the analysis of 1099 longitudinal samples. MM patients showed limited B-cell expansion linked to lower anti-RBD and anti-S antibody titers after the first two doses and booster. The percentages of B cells and CD4⁺ T cells in the blood, as well as the absolute counts of B cells and dendritic cells, predicted vaccine immunogenicity at different time points. In contrast with the humoral response, the percentage and antigen-dependent differentiation of SARS-CoV-2-specific CD8⁺ T cells was not altered in MM patients. Taken together, this study defined the cellular composition associated with immune dysfunction in MM and provided biomarkers such as the B-cell percentage and absolute count to individualize vaccination calendars.

感染是多发性骨髓瘤 （MM） 死亡的主要原因。然而，与免疫功能障碍相关的细胞组成尚未确定。我们使用多维和计算流式细胞术分析了 MM （n = 28） 和 B 细胞慢性淋巴组织增生性疾病 （n = 53） 患者与医疗保健从业者 （n = 96） 患者外周血中的免疫特征。MM 患者表现出大多数细胞类型的分布改变 （41/56， 73%），尤其是在 B 细胞 （17/17） 和 T 细胞 （20/30） 区室内。以 COVID-19 为案例研究，我们根据 1099 个纵向样本分析生成的 64,304 个数据点比较了对疫苗接种的免疫反应。MM 患者在前两剂和加强剂后表现出有限的 B 细胞扩增与较低的抗 RBD 和抗 S 抗体滴度有关。血液中 B 细胞和 CD4⁺ T 细胞的百分比，以及 B 细胞和树突状细胞的绝对计数，预测了不同时间点的疫苗免疫原性。与体液反应相反，MM 患者 SARS-CoV-2 特异性 CD8⁺ T 细胞的百分比和抗原依赖性分化没有改变。综上所述，本研究确定了与 MM 免疫功能障碍相关的细胞组成，并提供了 B 细胞百分比和绝对计数等生物标志物来个性化疫苗接种日历。