GSK, Rockville, MD, USA.
Department of Hematology, Ankara University Medicine Faculty, Ankara, Turkey.
Lancet Infect Dis. 2019 Sep;19(9):988-1000. doi: 10.1016/S1473-3099(19)30163-X. Epub 2019 Aug 6.
The adjuvanted recombinant zoster vaccine (Shingrix) can prevent herpes zoster in older adults and autologous haemopoietic stem cell transplant recipients. We evaluated the safety and immunogenicity of this vaccine in adults with haematological malignancies receiving immunosuppressive cancer treatments.
In this phase 3, randomised, observer-blind, placebo-controlled study, done at 77 centres worldwide, we randomly assigned (1:1) patients with haematological malignancies aged 18 years and older to receive two doses of the adjuvanted recombinant zoster vaccine or placebo 1-2 months apart during or after immunosuppressive cancer treatments, and stratified participants according to their underlying diseases. The co-primary objectives of the study were the evaluation of safety and reactogenicity of the adjuvanted recombinant zoster vaccine compared with placebo from the first vaccination up to 30 days after last vaccination in all participants; evaluation of the proportion of participants with a vaccine response in terms of anti-glycoprotein E humoral immune response to the adjuvanted recombinant zoster vaccine at month 2 in all participants, excluding those with non-Hodgkin B-cell lymphoma and chronic lymphocytic leukaemia; and evaluation of the anti-glycoprotein E humoral immune responses to the vaccine compared with placebo at month 2 in all participants, excluding those with non-Hodgkin B-cell lymphoma and chronic lymphocytic leukaemia. We assessed immunogenicity in the per-protocol cohort for immunogenicity and safety in the total vaccinated cohort. The study is registered with ClinicalTrials.gov, number NCT01767467, and with the EU Clinical Trials Register, number 2012-003438-18.
Between March 1, 2013, and Sept 10, 2015, we randomly assigned 286 participants to adjuvanted recombinant zoster vaccine and 283 to placebo. 283 in the vaccine group and 279 in the placebo group were vaccinated. At month 2, 119 (80·4%, 95% CI 73·1-86·5) of 148 participants had a humoral vaccine response to adjuvanted recombinant zoster vaccine, compared with one (0·8%, 0·0-4·2) of 130 participants in the placebo group, and the adjusted geometric mean anti-glycoprotein E antibody concentration was 23 132·9 mIU/mL (95% CI 16 642·8-32 153·9) in the vaccine group and 777·6 mIU/mL (702·8-860·3) in the placebo group (adjusted geometric mean ratio 29·75, 21·09-41·96; p<0·0001) in all patients, excluding those with non-Hodgkin B-cell lymphoma and chronic lymphocytic leukaemia. Humoral and cell-mediated immune responses persisted above baseline until month 13 in all strata and, as expected, vaccine was more reactogenic than placebo (within 7 days after vaccination pain was reported by 221 [79·5%] of 278 vaccine group participants and 45 [16·4%] of 274 placebo group participants; fatigue was reported by 162 [58·3%] of 278 vaccine group participants and 102 [37·2%] of 274 placebo group participants). Incidences of unsolicited or serious adverse events, potential immune-mediated diseases, disease-related events, and fatal serious adverse events were similar between the groups.
The immunocompromised adult population with haematological malignancies is at high risk for herpes zoster. The adjuvanted recombinant zoster vaccine, which is currently licensed in certain countries for adults aged 50 years and older, is likely to benefit this population.
GlaxoSmithKline Biologicals SA.
佐剂重组带状疱疹疫苗（Shingrix）可预防老年人和自体造血干细胞移植受者的带状疱疹。我们评估了该疫苗在接受免疫抑制癌症治疗的血液恶性肿瘤患者中的安全性和免疫原性。
在这项在全球 77 个中心进行的 3 期、随机、观察者盲法、安慰剂对照研究中，我们将年龄在 18 岁及以上的患有血液恶性肿瘤的患者按照 1:1 的比例随机分配，接受佐剂重组带状疱疹疫苗或安慰剂，在免疫抑制癌症治疗期间或之后间隔 1-2 个月接种两剂，并根据基础疾病进行分层。研究的主要次要目标是从第一次接种到所有参与者最后一次接种后 30 天内，评估佐剂重组带状疱疹疫苗与安慰剂相比的安全性和反应原性；评估所有参与者中，基于抗糖蛋白 E 体液免疫反应的疫苗接种者比例，在所有参与者中（不包括非霍奇金 B 细胞淋巴瘤和慢性淋巴细胞白血病患者）在第 2 个月；评估所有参与者中，与安慰剂相比，第 2 个月的抗糖蛋白 E 体液免疫反应，在所有参与者中（不包括非霍奇金 B 细胞淋巴瘤和慢性淋巴细胞白血病患者）。我们在方案规定的队列中评估了免疫原性，在总接种疫苗的队列中评估了安全性。该研究在 ClinicalTrials.gov 注册，编号为 NCT01767467，并在欧盟临床试验注册中心注册，编号为 2012-003438-18。
2013 年 3 月 1 日至 2015 年 9 月 10 日，我们将 286 名参与者随机分配至佐剂重组带状疱疹疫苗组和 283 名安慰剂组。283 名疫苗组和 279 名安慰剂组接受了疫苗接种。在第 2 个月，148 名参与者中有 119 名（80.4%，95%CI73.1-86.5）对佐剂重组带状疱疹疫苗有体液疫苗反应，而安慰剂组中有 130 名参与者中有 1 名（0.8%，0.0-4.2），疫苗组的调整后的几何平均抗糖蛋白 E 抗体浓度为 23132.9 mIU/mL（95%CI16642.8-32153.9），安慰剂组为 777.6 mIU/mL（702.8-860.3）（调整后的几何平均比 29.75，21.09-41.96；p<0.0001），所有患者，不包括非霍奇金 B 细胞淋巴瘤和慢性淋巴细胞白血病患者。在所有分层中，体液和细胞介导的免疫反应均高于基线，直至第 13 个月，与安慰剂相比，疫苗的反应原性更高（接种后 7 天内，278 名疫苗组参与者中有 221 名（79.5%）和 274 名安慰剂组参与者中有 45 名（16.4%）报告疼痛；278 名疫苗组参与者中有 162 名（58.3%）和 274 名安慰剂组参与者中有 102 名（37.2%）报告疲劳）。两组间未报告或严重不良事件、潜在免疫介导性疾病、疾病相关事件和致命严重不良事件的发生率相似。
患有血液恶性肿瘤的免疫功能低下的成年人群带状疱疹的风险很高。佐剂重组带状疱疹疫苗目前在某些国家批准用于 50 岁及以上的成年人，可能对这一人群有益。
葛兰素史克生物制品有限公司。
