Martac Ioana, Beer Sina A, Schenk Aileen, Ahmad Osama, Maier Claus-Philipp, Demirel Gülay, Preuß Beate, Klein Reinhild, Stanger Anna M P, Besemer Britta, Hensen Luca, Lengerke Claudia
Department of Internal Medicine II, Hematology, Oncology, Clinical Immunology and Rheumatology, University Hospital Tübingen, Tübingen, Germany.
Department of General Pediatrics, Hematology/Oncology, Children's University Hospital Tuebingen, Tübingen, Germany.
Front Immunol. 2024 Dec 18;15:1510942. doi: 10.3389/fimmu.2024.1510942. eCollection 2024.
Multiple myeloma (MM) is an uncontrolled plasma cell proliferation in the bone marrow, leading to immune dysregulation with impaired humoral immune responses. Conversely, cellular-based responses play a vital role in MM patients. However, the extent and duration of cellular-induced protection remain unclear to date. Here, immunomodulatory drugs (IMiDs) like Lenalidomide (Lena) become interesting, as they may have stimulatory effects on T-cell functioning.
In this study we investigated immune responses elicited by COVID-19 vaccine or infection comparing 43 healthy volunteers (avg. 35y, 72.1% female, 81.4% previously COVID-19 infected), with 41 MM patients under Lena maintenance therapy (avg. 63.8y, 51.2% female, 61% previously COVID-19 infected). Humoral responses to SARS-CoV-2 spike (S), spike-RBD, and nucleocapsid (N) were measured via ELISA in subjects' plasma. Freshly isolated PBMCs, incubated with SARS-CoV-2 peptides (N, S), activation induced marker (AIM) assays and flow cytometry, allowed us to assess cellular responses (CD8 T, T: CD4 T (follicular) helper).
Whereas healthy controls showed significant better humoral responses (N IgA p<0.001), T cell responses were robust in the MM group (higher S-act. T, p<0.001). Stratified by COVID-19 status, the MM group showed higher N-act. T (p=0.03). These results were unchanged comparing a Lena intake with Lena break around vaccination.
Taken together, MM patients under Lena therapy exhibit weakened antibody production but present a robust T cell response following SARS-COV-2 infection or vaccination. Our results highlight the importance of vaccination in this subgroup and moreover, argue against a Lena intake break around the time of vaccination.
多发性骨髓瘤（MM）是骨髓中浆细胞的失控增殖，导致免疫失调，体液免疫反应受损。相反，基于细胞的反应在MM患者中起着至关重要的作用。然而，细胞诱导的保护作用的程度和持续时间至今仍不清楚。在这里，像来那度胺（Lena）这样的免疫调节药物变得很有趣，因为它们可能对T细胞功能有刺激作用。
在本研究中，我们比较了43名健康志愿者（平均35岁，72.1%为女性，81.4%曾感染过COVID-19）和41名接受Lena维持治疗的MM患者（平均63.8岁，51.2%为女性，61%曾感染过COVID-19），调查了COVID-19疫苗或感染引发的免疫反应。通过ELISA法检测受试者血浆中对严重急性呼吸综合征冠状病毒2（SARS-CoV-2）刺突蛋白（S）、刺突蛋白受体结合域（RBD）和核衣壳蛋白（N）的体液反应。新鲜分离的外周血单个核细胞（PBMC）与SARS-CoV-2肽（N、S）一起孵育，通过激活诱导标志物（AIM）检测和流式细胞术，使我们能够评估细胞反应（CD8 T细胞、T：CD4 T（滤泡）辅助细胞）。
健康对照组的体液反应明显更好（N IgA p<0.001），而MM组的T细胞反应很强（S激活的T细胞更高，p<0.001）。按COVID-19状态分层，MM组的N激活的T细胞更高（p=0.03）。比较接种疫苗时服用Lena和停用Lena的情况，这些结果没有变化。
综上所述，接受Lena治疗的MM患者抗体产生减弱，但在感染SARS-CoV-2或接种疫苗后呈现出强烈的T细胞反应。我们的结果强调了在这一亚组中接种疫苗的重要性，此外，反对在接种疫苗时停用Lena。
