Fifth-week immunogenicity and safety of anti-SARS-CoV-2 BNT162b2 vaccine in patients with multiple myeloma and myeloproliferative malignancies on active treatment: preliminary data from a single institution.
Fifth-week immunogenicity and safety of anti-SARS-CoV-2 BNT162b2 vaccine in patients with multiple myeloma and myeloproliferative malignancies on active treatment: preliminary data from a single institution.
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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。
DOI：
10.1186/s13045-021-01090-6
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发表时间：
2021-05-17
影响因子：
28.5
通讯作者：
Mengarelli A
中科院分区：
文献类型：
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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
BNT 162 b2 mRNA疫苗在血液病患者中的安全性和免疫原性尚不清楚;在42例多发性骨髓瘤（MM）和50例骨髓增生性恶性肿瘤（MPM）（20例慢性髓性白血病和30例骨髓增生性肿瘤）患者中前瞻性评价了两者，所有患者均接受积极抗癌治疗，并与36例未患癌症的老年对照组进行了比较。排除了SARS-CoV-2基础血清学和/或分子学（鼻/咽拭子）阳性的受试者。主要终点是比较第一次给药后3周和5周时队列中中和抗SARS-CoV-2 IgG的滴度和血清保护率。使用LIAISON® SARS-CoV-2 S1/S2 IgG检测试剂盒进行滴定，该试剂盒是FDA批准的一种定量荧光免疫测定法，其依据是截止值为15 Au/mL的检测试剂盒与比例为1：40的空斑减少中和试验90%之间一致性的可靠证据（94.4%）。假设临界值为15 Au/mL，以区分具有保护性滴度的疫苗接种应答者。使用Fisher精确检验和适当的Mann-Whitney检验比较队列。分别通过Wilcoxon和McNemar检验比较每个队列中第1次和第2次给药后的几何平均浓度（GMC）、几何平均比值和缓解率。第5周时，老年对照组IgG的GMC为353.3 Au/mL，MM组为106.7（p = 0.003），MPM患者为172.9（p = 0.049）。在临界值15 Au/mL时，对照组的血清保护率为100%，而MM组为78.6%（p = 0.003），MPM患者为88%（p = 0.038）。就IgG滴度的对数而言，在广义多变量线性模型中，未观察到性别效应（p = 0.913），而随着年龄的增加（p < 0.001）和相对于对照组（MM：p < 0.001和MPM：p < 0.001），疾病队列中存在滴度降低的显著趋势。在MM患者中，正在进行的非达雷妥尤单抗治疗与更高的缓解可能性相关（p = 0.003）。在每个时间点，拭子结果均为阴性。未观察到安全性问题。BNT 162 b2已被证明在不同的群体中具有不同程度的免疫原性。在MPM患者中，缓解率为88%，且稳健。MM患者的反应明显较低，特别是那些接受抗CD 38治疗的患者。应建议后一类患者无论疫苗接种情况如何，都要保持口罩和社交距离，其同居家庭成员也需要接种疫苗，以降低家庭传染的风险。可以考虑额外的加强和滴度监测。试验注册研究于二零二一年一月获拉齐奥大区IRCCS中央伦理委员会正式批准（Prot. N-1463/21）。
Safety and immunogenicity of BNT162b2 mRNA vaccine are unknown in hematological patients; both were evaluated prospectively in 42 patients with multiple myeloma (MM) and 50 with myeloproliferative malignancies (MPM) (20 chronic myeloid leukemias and 30 myeloproliferative neoplasms), all of them on active anti-cancer treatment, in comparison with 36 elderly controls not suffering from cancer. Subjects serologically and/or molecularly (by nasal/throat swab) positives at basal for SARS-CoV-2 were excluded. Primary endpoint was to compare titers of neutralizing anti-SARS-CoV-2 IgG and seroprotection rates among the cohorts at 3 and 5 weeks from first dose. Titration was done using LIAISON® SARS-CoV-2 S1/S2 IgG test, a quantitative chemiluminescent immunoassay approved by FDA on the basis of robust evidences of concordance (94.4%) between the test at cutoff of 15 AU/mL and the Plaque Reduction Neutralization Test 90% at 1:40 ratio. Cutoff of 15 AU/mL was assumed to discriminate responders to vaccination with a protective titer. Cohorts were compared using Fisher’ exact test and the Mann–Whitney test as appropriated. Geometric mean concentrations (GMCs), geometric mean ratios and response rates after 1st and 2nd dose were compared in each cohort by Wilcoxon and McNemar tests, respectively. At 5 weeks, GMC of IgG in elderly controls was 353.3 AU/mL versus 106.7 in MM (p = 0.003) and 172.9 in MPM patients (p = 0.049). Seroprotection rate at cutoff of 15 AU/mL was 100% in controls compared to 78.6% in MM (p = 0.003) and 88% in MPM patients (p = 0.038). In terms of logarithm of IgG titer, in a generalized multivariate linear model, no gender effect was observed (p = 0.913), while there was a significant trend toward lower titers by increasing age (p < 0.001) and in disease cohorts with respect to controls (MM: p < 0.001 and MPM: p < 0.001). An ongoing treatment without daratumumab was associated with higher likelihood of response in MM patients (p = 0.003). No swabs resulted positive on each time point. No safety concerns were observed. BNT162b2 has demonstrated to be immunogenic at different extent among the cohorts. Response was 88% and robust in MPM patients. MM patients responded significantly less, particularly those on anti-CD38-based treatment. These latter patients should be advised to maintain masks and social distancing regardless of vaccination status, and their cohabiting family members need to be vaccinated in order to reduce the risk of contagion from the family. Additional boosters and titer monitoring could be considered. Trial registration Study was formally approved by the IRCCS Central Ethical Committee of Regione Lazio in January 2021 (Prot. N-1463/21).
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BNT162B2 mRNA COVID-19疫苗的安全性和功效。
DOI：
10.1056/nejmoa2034577
发表时间：
2020-12-31
期刊：
The New England journal of medicine
影响因子：
--
作者：
Polack FP;Thomas SJ;Kitchin N;Absalon J;Gurtman A;Lockhart S;Perez JL;Pérez Marc G;Moreira ED;Zerbini C;Bailey R;Swanson KA;Roychoudhury S;Koury K;Li P;Kalina WV;Cooper D;Frenck RW Jr;Hammitt LL;Türeci Ö;Nell H;Schaefer A;Ünal S;Tresnan DB;Mather S;Dormitzer PR;Şahin U;Jansen KU;Gruber WC;C4591001 Clinical Trial Group
通讯作者：
C4591001 Clinical Trial Group
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
影响因子：
11.4
作者：
Ludwig H;Boccadoro M;Moreau P;San-Miguel J;Cavo M;Pawlyn C;Zweegman S;Facon T;Driessen C;Hajek R;Dimopoulos MA;Gay F;Avet-Loiseau H;Terpos E;Zojer N;Mohty M;Mateos MV;Einsele H;Delforge M;Caers J;Weisel K;Jackson G;Garderet L;Engelhardt M;van de Donk N;Leleu X;Goldschmidt H;Beksac M;Nijhof I;Abildgaard N;Bringhen S;Sonneveld P
通讯作者：
Sonneveld P
影响因子：
28.5
作者：
Hwang JK;Zhang T;Wang AZ;Li Z
通讯作者：
Li Z
DOI：
10.1093/annonc/mdy117
发表时间：
2018-06-01
期刊：
Annals of oncology : official journal of the European Society for Medical Oncology
影响因子：
--
作者：
Rieger CT;Liss B;Mellinghoff S;Buchheidt D;Cornely OA;Egerer G;Heinz WJ;Hentrich M;Maschmeyer G;Mayer K;Sandherr M;Silling G;Ullmann A;Vehreschild MJGT;von Lilienfeld-Toal M;Wolf HH;Lehners N;German Society of Hematology and Medical Oncology Infectious Diseases Working Group (AGIHO)
通讯作者：
German Society of Hematology and Medical Oncology Infectious Diseases Working Group (AGIHO)