Martino Enrica Antonia, Vigna Ernesto, Bruzzese Antonella, Amodio Nicola, Lucia Eugenio, Olivito Virginia, Labanca Caterina, Caserta Santino, Mendicino Francesco, Morabito Fortunato, Gentile Massimo
Hematology Unit, Department of Onco-Hematology, Cosenza, Italy.
Department of Experimental and Clinical Medicine, University of Catanzaro, Catanzaro, Italy.
Eur J Haematol. 2025 Oct;115(4):334-343. doi: 10.1111/ejh.70013. Epub 2025 Jul 26.
Multiple myeloma (MM) is a hematological malignancy characterized by profound immunosuppression resulting from both disease-related mechanisms and treatment-induced immune dysfunction. This compromised immune status markedly increases susceptibility to infections, a leading cause of morbidity and mortality in MM patients. While vaccination represents a cornerstone of infection prevention, standard immunization strategies often yield suboptimal responses in this population.
This review synthesizes current evidence on the immunological barriers and clinical effectiveness of vaccination in MM. We evaluate vaccines targeting influenza, Streptococcus pneumoniae, SARS-CoV-2, and other relevant pathogens, and explore determinants influencing vaccine efficacy, including optimal timing, formulation, and patient-specific immune parameters.
A comprehensive literature review was conducted, encompassing clinical trials, retrospective cohort studies, expert consensus guidelines, and population-based data. Extracted outcomes included serological responses, infection-related events, and vaccine safety in MM patients.
Patients with MM exhibit impaired vaccine responses due to hypogammaglobulinemia, T- and B-cell dysfunction, and therapy-induced lymphodepletion. Despite modest immunogenicity, influenza and pneumococcal vaccines reduce respiratory infections and hospitalizations. Sequential administration of PCV13 followed by PPSV23, as well as post-autologous stem cell transplantation (ASCT) three-dose regimens, is associated with reduced pneumonia incidence. COVID-19 vaccines elicit variable responses, particularly in patients on anti-CD38 or BCMA-targeted therapies, highlighting the need for booster doses and, in selected cases, prophylactic monoclonal antibodies. Vaccines against herpes zoster, hepatitis B, and Haemophilus influenzae type B are also recommended, particularly around ASCT. Immunophenotypic markers such as CD19+ B-cell and CD4+ T-cell counts are predictive of vaccine responsiveness, supporting immune profiling as a tool for individualized vaccination planning.
Vaccination remains a critical component of infection prevention in MM. Although immunogenicity may be attenuated, clinical benefits-namely, reduced infection burden and healthcare utilization-support broad vaccine implementation. A personalized approach, considering the treatment phase, disease control, and immune status, is essential to optimize vaccine effectiveness. Ongoing research into high-dose, adjuvanted, and next-generation vaccines is critical to enhance protection in this vulnerable population.
多发性骨髓瘤（MM）是一种血液系统恶性肿瘤，其特征为因疾病相关机制和治疗诱导的免疫功能障碍导致严重免疫抑制。这种受损的免疫状态显著增加了感染易感性，而感染是MM患者发病和死亡的主要原因。虽然疫苗接种是预防感染的基石，但标准免疫策略在该人群中往往产生次优反应。
本综述综合了关于MM中疫苗接种的免疫障碍和临床效果的现有证据。我们评估针对流感、肺炎链球菌、严重急性呼吸综合征冠状病毒2（SARS-CoV-2）及其他相关病原体的疫苗，并探讨影响疫苗效力的决定因素，包括最佳时机、制剂和患者特异性免疫参数。
进行了全面的文献综述，涵盖临床试验、回顾性队列研究、专家共识指南和基于人群的数据。提取的结果包括MM患者的血清学反应、感染相关事件和疫苗安全性。
MM患者由于低丙种球蛋白血症、T细胞和B细胞功能障碍以及治疗诱导的淋巴细胞耗竭而表现出疫苗反应受损。尽管免疫原性适中，但流感疫苗和肺炎球菌疫苗可减少呼吸道感染和住院次数。13价肺炎球菌结合疫苗（PCV13）后序贯接种23价肺炎球菌多糖疫苗（PPSV23）以及自体造血干细胞移植（ASCT）后的三剂方案与肺炎发病率降低相关。2019冠状病毒病（COVID-19）疫苗引发的反应各不相同，尤其是在接受抗CD38或靶向B细胞成熟抗原（BCMA）治疗的患者中，这凸显了加强剂量的必要性，在某些情况下还需要预防性单克隆抗体。还建议接种带状疱疹疫苗、乙型肝炎疫苗和B型流感嗜血杆菌疫苗，尤其是在ASCT前后。免疫表型标志物如CD19+B细胞和CD4+T细胞计数可预测疫苗反应性，支持将免疫谱分析作为个性化疫苗接种计划的工具。
疫苗接种仍然是MM感染预防的关键组成部分。尽管免疫原性可能减弱，但临床益处——即减轻感染负担和减少医疗保健利用——支持广泛实施疫苗接种。考虑治疗阶段、疾病控制和免疫状态的个性化方法对于优化疫苗效力至关重要。对高剂量、佐剂和下一代疫苗的持续研究对于增强对这一脆弱人群的保护至关重要。
