Impact of anti-CD20 monoclonal antibodies on serologic response to BNT162b2 vaccine in B-cell Non-Hodgkin's lymphomas.
Impact of anti-CD20 monoclonal antibodies on serologic response to BNT162b2 vaccine in B-cell Non-Hodgkin's lymphomas.
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DOI：
10.1038/s41375-021-01418-8
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发表时间：
2022-03
期刊：
影响因子：
11.4
通讯作者：
Mengarelli A
中科院分区：
文献类型：
--
作者：
Marchesi F;Pimpinelli F;Giannarelli D;Ronchetti L;Papa E;Falcucci P;Pontone M;Di Domenico EG;di Martino S;Laquintana V;Mandoj C;Conti L;Cordone I;La Malfa A;Viggiani C;Renzi D;Palombi F;Romano A;Pisani F;Gumenyuk S;Di Bella O;Vujovic B;Morrone A;Ciliberto G;Ensoli F;Mengarelli A
恶性血液病患者有患严重新冠肺炎的风险，可能会优先接种疫苗，最好是使用信使核糖核酸疫苗。根据伦理考虑和卫生当局(HA)的严格适应症，正在进行淋巴清除治疗的患者也接受了疫苗接种。在意大利，针对新冠肺炎的国家计划要求尽快为正在接受免疫抑制或骨髓抑制药物治疗的血液病患者或在此类治疗结束后六个月内接种疫苗，并要求在移植后三个月内为干细胞移植患者接种疫苗。淋巴癌已被确定为对抗SARS-CoV-2疫苗抗体反应不足的风险特别大。在慢性淋巴细胞白血病(CLL)患者中，这种反应明显受损，并受到疾病活动和治疗的影响[1，2]。接受抗CD38抗体治疗的多发性骨髓瘤患者也有部分和微弱的反应[3]。抗SARS-CoV-2疫苗在B细胞非霍奇金淋巴瘤(B-NHL)患者中的免疫原性首次观察表明，接受抗B细胞单抗(MoAbbs)的受试者对BNT162b2的体液反应严重受损[4-6]。考虑到在新冠肺炎以外的接种环境中，暴露于抗CD20和抗CD22moAbb、抗CD19双功能抗体和嵌合抗原受体T细胞的患者被建议推迟到暂停治疗后六个月，这种有害影响并不令人惊讶[7，8]。根据我们的单中心前瞻性队列研究，拉齐奥地区IRCCS中央伦理委员会于2021年1月正式批准(Prot.在此，我们提供了连续68例B-NHL患者对BNT162b2(两次肌肉注射，每剂相隔三周，30微克)的血清学反应的数据，这些患者正在接受或以前接受基于抗CD20的治疗(利妥昔单抗或obinutuzumab)，主要目的是探讨抗CD20单抗对疫苗免疫原性的影响，并确定没有抗CD20注射所需的时间间隔(TI)以减轻这种影响。分别于免疫前(第0天，第1针，时间点[TP]0)、免疫后3周(第2针，TP1)、免疫后2周(第35天，TP2)、9周(第84天，TP3)检测抗SARS-CoV-2S1/S2Ig G。所有参与者都被要求在前两个TPS以及每个临床怀疑新冠肺炎或随后进入医院的病例中提供鼻咽拭子，以进行SARS-CoV-2感染的分子检测。基础抗SARS-CoV-2抗体阳性被排除在分析标准之外。抗SARS-CoV-2S_1/S_2免疫球蛋白检测采用意大利萨卢吉亚市DiaSorin®化学发光免疫分析系统。根据制造商L技术手册，Contison®SARS-CoV-2 S1/S2Ig G检测结果为阳性，信号为15AU/mL或更高[https://www.迪亚索林。Com/en/immunodiagnostic-solutions/clinical-areas/infectious-diseases/covid-19].根据Wilcoxon的统计数据(Torsten Hothorn[2017])，最后一剂抗CD20抗体和疫苗接种之间最有用的感染指数是根据Wilcoxon的统计数据确定的，即最佳区分应答者和无应答者的截止值。最大统计：最大选择的等级统计。R程序包版本0.7-25。Https://CRAN.R-项目。Org/Package=Maxstat)。
Patients with hematological malignancies are at risk of severe COVID-19 and candidate to priority vaccination policies, preferably with a mRNA vaccine. In light of ethical considerations and strict indications of Health Authorities (HA), also patients with ongoing lymphodepleting therapy underwent vaccination. In Italy, the national plan against COVID-19 required to proceed as soon as possible with the vaccination of hematological patients in treatment with immunosuppressive or myelosuppressive drugs or within six months from the end of such treatment, and of stem cell transplanted patients after three months from transplant. Lymphoid cancers have been identified as being particularly at risk of inadequate antibody response to anti-SARS-CoV-2 vaccines. In patients with chronic lymphocytic leukemia (CLL), the response is markedly impaired and affected by disease activity and treatment [1, 2]. Multiple myeloma patients on anti-CD38 antibody therapy also respond partially and weakly [3]. The first observations on immunogenicity of anti-SARS-CoV-2 vaccines in patients with B-cell Non-HodgkinLs Lymphoma (B-NHL) indicate that humoral response to BNT162b2 is deeply impaired in subjects undergoing anti-B cells monoclonal antibodies (moAbs)[4-6]. Such detrimental effect is not surprising, considering that a postponement to six months after therapy suspension has been suggested in patients exposed to anti-CD20 and anti-CD22 moAbs, anti-CD19 bispecific antibody and chimeric antigen receptor T-cells in vaccination settings other than COVID-19 [7, 8]. According to our mono-centric prospective cohort study formally approved by the IRCCS Central Ethical Committee of Regione Lazio in January 2021 (Prot. N-1463/21), herein we present data on the serologic response to BNT162b2 (two intramuscular injections of 30 µg per dose three weeks apart) in 68 consecutive patients with B-NHL on anti-CD20-based therapy (rituximab or obinutuzumab) either ongoing or previously administered, with the primary objective to explore the impact of anti-CD20 moAbs on vaccine immunogenicity and identify the time interval (TI) free from an anti-CD20 administration required for mitigating such effect. Anti SARS-CoV-2 S1/S2 IgG were evaluated before vaccination (day 0, first injection, time point [TP] 0), after three weeks from vaccination (day 21, second injection, TP1), and two-weeks (day 35, TP2) and nine-weeks (day 84, TP3) post-booster. All participants were asked to provide nose and throat swabs for molecular determination of a SARS-CoV-2 infection at each of the first two TPs and in every case of clinical suspicion of COVID-19 or hospital access subsequently. A positive determination of anti SARS-CoV-2 IgG at basal was an exclusion criterion from the analysis. Anti SARS-CoV-2 S1/S2 IgG determination was performed by the Liaison® SARS-CoV-2 S1/S2 IgG assay (DiaSorin®, Saluggia, Italy), a quantitative chemiluminescent immunoassay approved by FDA. According to the manufacturersL technical manual, the result of a Liaison® SARS-CoV-2 S1/S2 IgG test is positive with a signal of 15 AU/mL or higher [https://www. diasorin. com/en/immunodiagnostic-solutions/clinical-areas/infectious-diseases/covid-19]. The most useful TI between last dose of anti-CD20 and vaccination for categorization purposes was identified at the cutoff value which best separated responders versus non-responders according to the Wilcoxon statistic (Torsten Hothorn [2017]. maxstat: Maximally Selected Rank Statistics. R package version 0.7-25. https://CRAN. R-project. org/package= maxstat).
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影响因子：
10.1
作者：
Gurion R;Rozovski U;Itchaki G;Gafter-Gvili A;Leibovitch C;Raanani P;Ben-Zvi H;Szwarcwort M;Taylor-Abigadol M;Dann EJ;Horesh N;Inbar T;Tzoran I;Lavi N;Fineman R;Ringelstein-Harlev S;Horowitz NA
通讯作者：
Horowitz NA
影响因子：
20.3
作者：
Herishanu Y;Avivi I;Aharon A;Shefer G;Levi S;Bronstein Y;Morales M;Ziv T;Shorer Arbel Y;Scarfò L;Joffe E;Perry C;Ghia P
通讯作者：
Ghia P
抗SARS-COV-2 BNT162B2疫苗的第五周免疫原性和安全性多发性骨髓瘤和骨髓增生性恶性肿瘤患者的主动治疗中的疫苗：来自单个机构的初步数据。
影响因子：
28.5
作者：
Pimpinelli F;Marchesi F;Piaggio G;Giannarelli D;Papa E;Falcucci P;Pontone M;Di Martino S;Laquintana V;La Malfa A;Di Domenico EG;Di Bella O;Falzone G;Ensoli F;Vujovic B;Morrone A;Ciliberto G;Mengarelli A
通讯作者：
Mengarelli A
影响因子：
7.5
作者：
Perry C;Luttwak E;Balaban R;Shefer G;Morales MM;Aharon A;Tabib Y;Cohen YC;Benyamini N;Beyar-Katz O;Neaman M;Vitkon R;Keren-Khadmy N;Levin M;Herishanu Y;Avivi I
通讯作者：
Avivi I
影响因子：
7.5
作者：
Vijenthira A;Gong I;Betschel SD;Cheung M;Hicks LK
通讯作者：
Hicks LK