Rosati Margherita, Terpos Evangelos, Bear Jenifer, Burns Robert, Devasundaram Santhi, Ntanasis-Stathopoulos Ioannis, Gavriatopoulou Maria, Kastritis Efstathios, Dimopoulos Meletios-Athanasios, Pavlakis George N, Felber Barbara K
Human Retrovirus Section, Vaccine Branch, Center for Cancer Research, National Cancer Institute at Frederick, Frederick, MD 21702, USA.
Department of Clinical Therapeutics, School of Medicine, National and Kapodistrian University of Athens, 117 27 Athens, Greece.
Cancers (Basel). 2022 Nov 25;14(23):5816. doi: 10.3390/cancers14235816.
Patients with symptomatic monoclonal gammopathies have impaired humoral responses to COVID-19 vaccination. Their ability to recognize SARS-CoV-2 Omicron variants is of concern. We compared the response to BNT162b2 mRNA vaccinations of patients with multiple myeloma (MM, n = 60) or Waldenstrom's macroglobulinemia (WM, n = 20) with healthy vaccine recipients (n = 37). Patient cohorts on active therapy affecting B cell development had impaired binding and neutralizing antibody (NAb) response rate and magnitude, including several patients lacking responses, even after a 3rd vaccine dose, whereas non-B cell depleting therapies had a lesser effect. In contrast, MM and WM cohorts off-therapy showed increased NAb with a broad response range. ELISA Spike-Receptor Binding Domain (RBD) Ab titers in healthy vaccine recipients and patient cohorts were good predictors of the ability to neutralize not only the original WA1 but also the most divergent Omicron variants BA.4/5. Compared to WA1, significantly lower NAb responses to BA.4/5 were found in all patient cohorts on-therapy. In contrast, the MM and WM cohorts off-therapy showed a higher probability to neutralize BA.4/5 after the 3rd vaccination. Overall, the boost in NAb after the 3rd dose suggests that repeat vaccination of MM and WM patients is beneficial even under active therapy.
有症状的单克隆丙种球蛋白病患者对新冠疫苗的体液免疫反应受损。他们识别新冠病毒奥密克戎变种的能力令人担忧。我们比较了多发性骨髓瘤（MM，n = 60）或华氏巨球蛋白血症（WM，n = 20）患者与健康疫苗接种者（n = 37）对BNT162b2 mRNA疫苗的反应。接受影响B细胞发育的积极治疗的患者队列，其结合和中和抗体（NAb）反应率及反应强度受损，包括几名即使在接种第三剂疫苗后仍无反应的患者，而非B细胞耗竭疗法的影响较小。相比之下，未接受治疗的MM和WM队列显示NAb增加，反应范围广泛。健康疫苗接种者和患者队列中的ELISA刺突受体结合域（RBD）抗体滴度不仅是中和原始WA1毒株能力的良好预测指标，也是中和差异最大的奥密克戎变种BA.4/5能力的良好预测指标。与WA1相比，所有接受治疗的患者队列对BA.4/5的NAb反应显著降低。相比之下，未接受治疗的MM和WM队列在接种第三剂疫苗后中和BA.4/5的可能性更高。总体而言，第三剂疫苗接种后NAb的增强表明，即使在积极治疗下，对MM和WM患者进行重复接种也是有益的。
