Epidemiology and risk factors Epidemiology and risk factors

固形腫瘍

免疫抑制・化学療法施行中の固形腫瘍患者21

免疫抑制・化学療法を受けている固形腫瘍患者（18歳以上）を対象に、組換え帯状疱疹ワクチン (RZV)を0ヶ月および1～2ヶ月のスケジュールで2回筋肉内投与した場合の免疫原性および安全性を評価する無作為化観察者盲検プラセボ対照多施設共同第Ⅱ/Ⅲ相臨床試験。21,26,27

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試験デザイン21

study-design-to-asses-the-immunogenicity-and-safety-of-the-recombinant-zoster-vaccine-when-administered-intramuscularly-to-adults-aged-18-years-and-older-with-solid-tumours-receiving-chemotherapy.-adults-with-solid-tumours-undergoing-chemotherapy-were-randomised-four-to-four-to-one-to-one-to-receive-two-doses-of-either-the-recombinant-zoster-vaccine-or-placebo-one-to-two-months-apart.-the-first-two-groups-received-the-first-dose-between-8-and-30-days-before-the-start-of-their-chemotherapy-cycle-and-the-latter-two-groups-at-the-start-of-their-first-or-second-chemotherapy-cycle.-visits-were-carried-out-at-months-0,-1,-2,-7-and-13-and-blood-sampling-occurred-at-each-visit.- participants-were-contacted-by-telephone-between-the-last-two-visits.-the-follow-up-period-was-month-2-to-month-13-

*Blood samples were collected from a sub cohort of subjects at Visit 1, 2, 3 and 5 for cell-mediated immunity.
†Second dose administered between 1 and 2 months after the first vaccination, at the first day of a subsequent cycle of chemotherapy.
‡Visit 4 occurred within Months 4 to 13 for a blood sample at the start of the last cycle of chemotherapy (if at least 2 months after the previous blood sample).
RZV, recombinant zoster vaccine; YOA, years of age

stacked-column-chart-depicting-the-proportion-of-solid-tumour-diagnosis-in-all-study-participants.-breast-cancer-was-the-most-common-diagnosis-followed-by-colorectal-cancer-

*Includes gastric, endometrial, ovarian, head and neck, larynx, mouth, sinus, tonsil, liposarcoma myxoid, liver, oesophageal, renal, sarcoma, stomach, testicular embryonic carcinoma, thyroid, tongue, cervix, urothelial, uterine leiomyosarcoma.

RZV, recombinant zoster vaccine.

The figure has been independently created by GSK from Vink P. Poster 1349. Presented at IDWeek; 4–8 October, 2017; San Diego, CA, USA.

液性免疫応答21,27

column-graph-depicting-the-anti-glycoprotein-e-antibody-geometric-mean-concentration-in-patients-with-solid-tumours.-one-month-post-vaccine-dose-2,-the-pooled-anti-glycoprotein-e-antibody-geometric-mean-concentration-was-18292-milli-international-units-per-milliliter-and-remained-higher-in-the-vaccine-pre-chemo-group-than-in-the-vaccine-on-chemo-group.-patients-vaccinated-before-chemotherapy-showed-higher-antibody-levels-1-month-after-dose-1-and-1-month-after-dose-2,-compared-with-those-vaccinated-while-on-chemotherapy.-however,-the-levels-were-similar-at-month-12-after-two-dose-schedule-completion-

ATP cohort for humoral immunogenicity and humoral persistence.
ATP, according-to-protocol; gE, glycoprotein; GMC, geometric mean concentration; Mo, month; PI, post-dose 1; PII, post-dose 2; Pre, pre-vaccination; RZV, recombinant zoster vaccine

PRE-chemo群における細胞性免疫応答21,26,27

 

RZV-CMI

(N=25)

Placebo-CMI

(N=30)
Frequency of gE-specific CD4+ T cells, cells/million
Month 0

Number of patients analysed

Median (IQR)

25

127.3 (49.7–192.4)

27

104.8 (27.5–151.5)
Month 1

Number of patients analysed

Median (IQR)

25

391.9 (139.7–603.7)

30

50.0 (1.0–179.4)
Month 2

Number of patients analysed

Median (IQR)

22

778.8 (393.1–1098.2)

29

61.8 (17.4–139.5)
Month 13

Number of patients analysed

Median (IQR)

18

332.9 (114.9–604.6)

19

51.2 (1.0–288.6)

Frequencies of gE-specific CD4+ T cells per 106 total CD4+ T cells (ATP subcohort for CMI, PRE-chemo groups only). 
ATP cohort for humoral immunogenicity and humoral persistence.
ATP, according-to-protocol; CMI, cell-mediated immunity; gE, glycoprotein E; Mo, month; Pre, pre-vaccination Mo 0; Q, quartile; RZV, recombinant zoster vaccine.

液性および細胞性免疫応答は、最初のワクチン接種のタイミングが化学療法開始前か開始時かにかかわらず、ワクチン接種から12ヵ月後も持続しました。gE特異的CD4＋T細胞出現頻度は、18～49歳および50歳以上のRZV接種群で同程度でした。21,27

column-graphs-depicting-the-local-and-general-reactions-in-patients-with-solid-tumours-who-received-either-the-recombinant-zoster-vaccine-or-placebo.-in-patients-who-received-the-recombinant-zoster-vaccine-the-most-frequently-reported-local-adverse-reaction-was-pain-at-the-injection-site;-fatigue,-myalgia-and-gastrointestinal-symptoms-were-the-most-frequently-reported-general-reactions-

Figures adapted with permission from Vink P et al. Cancer 2019;125:1301–1312.
Grade 3 pain, pain that prevented normal activity; grade 3 redness/swelling, redness/swelling spreading beyond 100 mm of injection site; grade 3 fever >39.0°C.
AE, adverse event; GI, gastrointestinal (nausea, vomiting, diarrhoea and/or abdominal pain); RZV, recombinant zoster vaccine.

最も一般的な局所および全身性の有害事象は、注射部位の疼痛、疲労、筋肉痛でした。21,27 局所性および全身性の特定有害事象は、RZV 投与群ではプラセボ投与群よりも頻度が高かったものの、症状の強さは軽度から中等度であり、症状の持続期間の中央値は最大4日間であり一過的でした21,27。

column-graph-summarising-serious-adverse-events,-related-serious-adverse-events,-fatal-adverse-events,-potential-immune-mediated-diseases-and-unsolicited-adverse-events-in-patients-with-a-solid-tumour-who-received-either-the-recombinant-zoster-vaccine-or-placebo.-overall-incidences-of-serious-adverse-events,-deaths,-potential-immune-mediated-diseases-and-unsolicited-adverse-events-were-similar-between-the-recombinant-zoster-vaccine-and-placebo-groups-

AE, adverse event; pIMDs, potential immune-mediated diseases; RZV, recombinant zoster vaccine; SAE, serious adverse event.
The graph has been independently created by GSK from Zoster-028 Clinical Study Report 116427. Available at: https://gsk-clinicalstudyregister.com/files2/116427-Clinical-Study-Result-Summary.pdf (accessed May 2023) and Vink P, et al. Cancer. 2019;125(8):1301–1312.

AE、SAE、および死亡に至る有害事象の割合は、RZV群とプラセボ群で同程度でした。21
RZV 群、プラセボ群ともに、一般的な有害事象の症状の頻度は、免疫健常の高齢者と比較して高い結果でしたが、これは基礎疾患である悪性腫瘍や治療に関連した有害事象が多いことを示唆しています。21

自家造血幹細胞移植（auHSCT）患者におけるワクチンの試験概要・結果

血液悪性腫瘍患者におけるワクチンの試験概要・結果

固形腫瘍患者におけるワクチンの試験概要・結果

腎移植患者におけるワクチンの試験概要・結果

HIV感染症患者におけるワクチンの試験概要・結果

Abbreviations

AE, adverse event; ART, anti-retroviral therapy; ATP, according to protocol; BCL, B-cell lymphoma; CLL, chronic lymphocytic leukaemia; CMI, cell-mediated immunity; gE, glycoprotein E; GI, gastrointestinal; GMC, geometric mean concentration; HIV, human immunodeficiency virus; IQR, interquartile range; LL, lower limit; Mo, month; mTVC, modified total vaccinated cohort; pIMD, potential immune-mediated disease; PHN, post-herpetic neuralgia; Pre, pre-vaccination; Q, quartile; RZV, recombinat zoster vaccine; SAE, serious adverse event; TVC, total vaccinated cohort; UL, upper limit; VE, vaccine efficacy; VRR, vaccine response rate; YOA, years of age

AE, adverse event; ART, anti-retroviral therapy; ATP, according to protocol; BCL, B-cell lymphoma; CLL, chronic lymphocytic leukaemia; CMI, cell-mediated immunity; gE, glycoprotein E; GI, gastrointestinal; GMC, geometric mean concentration; HIV, human immunodeficiency virus; IQR, interquartile range; LL, lower limit; Mo, month; mTVC, modified total vaccinated cohort; pIMD, potential immune-mediated disease; PHN, post-herpetic neuralgia; Pre, pre-vaccination; Q, quartile; RZV, recombinat zoster vaccine; SAE, serious adverse event; TVC, total vaccinated cohort; UL, upper limit; VE, vaccine efficacy; VRR, vaccine response rate; YOA, years of age

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NX-JP-SGX-WCNT-230013 | November 2023