Safety and immunogenicity of one versus two doses of the COVID-19 vaccine BNT162b2 for patients with cancer: interim analysis of a prospective observational study.
Safety and immunogenicity of one versus two doses of the COVID-19 vaccine BNT162b2 for patients with cancer: interim analysis of a prospective observational study.
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DOI：
10.1016/s1470-2045(21)00213-8
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发表时间：
2021-06
期刊：
影响因子：
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通讯作者：
Irshad S
中科院分区：
文献类型：
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作者：
Monin L;Laing AG;Muñoz-Ruiz M;McKenzie DR;Del Molino Del Barrio I;Alaguthurai T;Domingo-Vila C;Hayday TS;Graham C;Seow J;Abdul-Jawad S;Kamdar S;Harvey-Jones E;Graham R;Cooper J;Khan M;Vidler J;Kakkassery H;Sinha S;Davis R;Dupont L;Francos Quijorna I;O'Brien-Gore C;Lee PL;Eum J;Conde Poole M;Joseph M;Davies D;Wu Y;Swampillai A;North BV;Montes A;Harries M;Rigg A;Spicer J;Malim MH;Fields P;Patten P;Di Rosa F;Papa S;Tree T;Doores KJ;Hayday AC;Irshad S
SARS-CoV-2疫苗在癌症患者中的有效性和安全性尚不清楚。我们旨在评估BNT 162 b2（Pfizer-BioNTech）疫苗在癌症患者中的安全性和免疫原性。在这项前瞻性观察性研究中，我们在2020年12月8日至2021年2月18日期间从三家伦敦医院招募了癌症患者和健康对照（主要是医护人员）。在2020年12月8日至12月29日期间接种疫苗的参与者接受了两次30 μg剂量的BNT 162 b2肌内注射，间隔21天;在此日期之后接种疫苗的患者仅接受了一次30 μg剂量，计划在12周时进行随访加强。在疫苗接种前以及首次疫苗接种后3周和5周采集血样。在可能的情况下，每10天或在有症状的COVID-19病例中进行一系列鼻咽实时RT-PCR（rRT-PCR）拭子检测。共同主要终点是首次接种BNT 162 b2疫苗后癌症患者对SARS-CoV-2刺突（S）蛋白的血清转化，以及21天后疫苗加强对血清转化的影响。所有具有可用数据的受试者均纳入安全性和免疫原性分析。在延迟（12周）疫苗加强后，正在进行进一步的血液采样。本研究在NHS健康研究机构和威尔士健康与护理研究中心注册（REC ID 20/HRA/2031）。151名癌症患者（95名实体癌患者和56名血液癌患者）和54名健康对照者入组。对于癌症疫苗接种患者的安全性和免疫原性的中期数据分析，分析了截至2021年3月19日获得的样本和数据。在排除了17名曾暴露于SARS-CoV-2的患者后，根据免疫原性分析（通过抗体血清转化或阳性rRT-PCR COVID-19拭子试验检测），三个队列中单次疫苗接种后约21天的阳性抗S IgG滴度比例为32（94%; 95% CI 81-98）; 56例实体癌患者中有21例（38%; 26-51）; 44例血液癌患者中有8例（18%; 10-32）。16名健康对照、25名实体癌患者和6名血液癌患者在第21天接受第二次给药。在21天疫苗加强后2周可获得血液样本的患者中，排除17名有既往自然SARS-CoV-2暴露证据的参与者，（95%; 95% CI 75-99）19例实体癌患者中，12例（100%; 76-100）的12名健康对照，和3名（60%; 23-88）的5例血液系统癌症患者血清阳性，相比之下，（30%; 17-47）的33，18（86%; 65-95）的21，和4（11%; 4-25）的36谁没有收到加强。该疫苗耐受性良好;在第一剂BNT 162 b2后，140名癌症患者中有75名（54%）没有报告毒性，在第二剂BNT 162 b2后，31名癌症患者中有22名（71%）没有报告毒性。同样，40名健康对照者中有15名（38%）在第一次给药后没有报告毒性，16名中有5名（31%）在第二次给药后没有报告毒性。首次给药后7天内的注射部位疼痛是最常报告的局部反应（65例癌症患者中有23例[35%]; 25例健康对照中有12例[48%]）。未报告疫苗相关死亡。在癌症患者中，一剂BNT 162 b2疫苗的效果很差。在第一次接种后第21天，实体癌患者在疫苗加强免疫的2周内免疫原性显著增加。这些数据支持优先考虑癌症患者早期（第21天）接种第二剂BNT 162 b2疫苗。伦敦国王学院、英国癌症研究所、威康信托基金会、玫瑰树信托基金会和弗朗西斯克里克研究所。
The efficacy and safety profiles of vaccines against SARS-CoV-2 in patients with cancer is unknown. We aimed to assess the safety and immunogenicity of the BNT162b2 (Pfizer–BioNTech) vaccine in patients with cancer. For this prospective observational study, we recruited patients with cancer and healthy controls (mostly health-care workers) from three London hospitals between Dec 8, 2020, and Feb 18, 2021. Participants who were vaccinated between Dec 8 and Dec 29, 2020, received two 30 μg doses of BNT162b2 administered intramuscularly 21 days apart; patients vaccinated after this date received only one 30 μg dose with a planned follow-up boost at 12 weeks. Blood samples were taken before vaccination and at 3 weeks and 5 weeks after the first vaccination. Where possible, serial nasopharyngeal real-time RT-PCR (rRT-PCR) swab tests were done every 10 days or in cases of symptomatic COVID-19. The coprimary endpoints were seroconversion to SARS-CoV-2 spike (S) protein in patients with cancer following the first vaccination with the BNT162b2 vaccine and the effect of vaccine boosting after 21 days on seroconversion. All participants with available data were included in the safety and immunogenicity analyses. Ongoing follow-up is underway for further blood sampling after the delayed (12-week) vaccine boost. This study is registered with the NHS Health Research Authority and Health and Care Research Wales (REC ID 20/HRA/2031). 151 patients with cancer (95 patients with solid cancer and 56 patients with haematological cancer) and 54 healthy controls were enrolled. For this interim data analysis of the safety and immunogenicity of vaccinated patients with cancer, samples and data obtained up to March 19, 2021, were analysed. After exclusion of 17 patients who had been exposed to SARS-CoV-2 (detected by either antibody seroconversion or a positive rRT-PCR COVID-19 swab test) from the immunogenicity analysis, the proportion of positive anti-S IgG titres at approximately 21 days following a single vaccine inoculum across the three cohorts were 32 (94%; 95% CI 81–98) of 34 healthy controls; 21 (38%; 26–51) of 56 patients with solid cancer, and eight (18%; 10–32) of 44 patients with haematological cancer. 16 healthy controls, 25 patients with solid cancer, and six patients with haematological cancer received a second dose on day 21. Of the patients with available blood samples 2 weeks following a 21-day vaccine boost, and excluding 17 participants with evidence of previous natural SARS-CoV-2 exposure, 18 (95%; 95% CI 75–99) of 19 patients with solid cancer, 12 (100%; 76–100) of 12 healthy controls, and three (60%; 23–88) of five patients with haematological cancers were seropositive, compared with ten (30%; 17–47) of 33, 18 (86%; 65–95) of 21, and four (11%; 4–25) of 36, respectively, who did not receive a boost. The vaccine was well tolerated; no toxicities were reported in 75 (54%) of 140 patients with cancer following the first dose of BNT162b2, and in 22 (71%) of 31 patients with cancer following the second dose. Similarly, no toxicities were reported in 15 (38%) of 40 healthy controls after the first dose and in five (31%) of 16 after the second dose. Injection-site pain within 7 days following the first dose was the most commonly reported local reaction (23 [35%] of 65 patients with cancer; 12 [48%] of 25 healthy controls). No vaccine-related deaths were reported. In patients with cancer, one dose of the BNT162b2 vaccine yields poor efficacy. Immunogenicity increased significantly in patients with solid cancer within 2 weeks of a vaccine boost at day 21 after the first dose. These data support prioritisation of patients with cancer for an early (day 21) second dose of the BNT162b2 vaccine. King's College London, Cancer Research UK, Wellcome Trust, Rosetrees Trust, and Francis Crick Institute.