TY - JOUR
T1 - Immunogenicity and safety of the adjuvanted recombinant zoster vaccine in adults with haematological malignancies
T2 - a phase 3, randomised, clinical trial and post-hoc efficacy analysis
AU - Dagnew, Alemnew F.
AU - Ilhan, Osman
AU - Lee, Won Sik
AU - Woszczyk, Dariusz
AU - Kwak, Jae Yong
AU - Bowcock, Stella
AU - Sohn, Sang Kyun
AU - Rodriguez Macías, Gabriela
AU - Chiou, Tzeon Jye
AU - Quiel, Dimas
AU - Aoun, Mickael
AU - Navarro Matilla, Maria Belen
AU - de la Serna, Javier
AU - Milliken, Samuel
AU - Murphy, John
AU - McNeil, Shelly A.
AU - Salaun, Bruno
AU - Di Paolo, Emmanuel
AU - Campora, Laura
AU - López-Fauqued, Marta
AU - El Idrissi, Mohamed
AU - Schuind, Anne
AU - Heineman, Thomas C.
AU - Van den Steen, Peter
AU - Oostvogels, Lidia
AU - Acar, Kadir
AU - Afanasyev, Boris
AU - Alonso Alonso, Aránzazu
AU - Anttila, Veli Jukka
AU - Barba Suñol, Pere
AU - Blesing, Norbert
AU - Comeau, Terrance
AU - del Campo, Teresa
AU - Disperati, Patricia
AU - Eek, Richard
AU - Eom, Hyeon Seok
AU - Gaidano, Gianluca
AU - Grosicki, Sebastian
AU - Guillaume, Thierry
AU - Homenda, Wojciech
AU - Hwang, William
AU - Ilyin, Nikolay
AU - Johnston, Anna
AU - Kim, Seok Jin
AU - Kuo, Ching Yuan
AU - Kuvshinov, Aleksey
AU - Lee, Dong Gun
AU - Lee, Jae Hoon
AU - Lee, Je Jung
AU - Lepretre, Stephane
AU - Lie, Albert Kwok Wai
AU - Lucchesi, Alessandro
AU - Masood, Ahmed
AU - Mir, Naheed
AU - Miranda Castillo, Anna Carolina
AU - Mullane, Kathleen
AU - Myasnikov, Alexandr
AU - Oña Navarrete, Raquel
AU - Pauksens, Karlis
AU - Peniket, Andrew
AU - Perez de Oteyza, Jaime
AU - Pohlreich, David
AU - Pullon, Humphrey
AU - Quittet, Philippe
AU - Rodon, Philippe
AU - Rombo, Lars
AU - Samoylova, Olga
AU - Sanmartin Berglund, Johan
AU - Schattner, Ariah
AU - Selleslag, Dominik
AU - Sinisalo, Marjatta
AU - Sultan, Faisal
AU - Theunissen, Koen
AU - Turner, Paul
AU - Wang, Po Nan
AU - Yáñez San Segundo, Lucrecia
AU - Young, Jo Anne
AU - Zachee, Pierre
AU - Zaja, Francesco
N1 - Funding Information:
AFD, LC, EDP, MEI, ML-F, AS, PVdS, BS, TCH, and LO were employees of the GSK group of companies at the time this study was designed, initiated, and conducted. AFD, LC, EDP, MEI, ML-F, AS, PVdS, and BS are employed by GSK. LO is an employee of CureVac as of March 1, 2018, and is inventor on a patent application related to the vaccine used in this study. TCH was a paid consultant for GSK during the development of this manuscript and is the co-inventor of a patent application related to the vaccine used in this study. AS, AFD, EDP, LC, MEI, PVdS, LO, TCH, and BS hold shares or stock options in GSK as part of their current or former employee remuneration. SAM declares that her institution has a clinical trial contract with Novartis and has received research grants for conduct of clinical trials by GSK, Merck, Pfizer, and Sanofi Pasteur. SAM received honoraria for participation in scientific advisory boards from GSK, Pfizer, Sanofi Pasteur, and Merck, and for provision of accredited continuing medical education to health-care professionals on adult immunisation and zoster vaccines. JM reports grants from GSK during the conduct of the study and personal fees for participation in Roche Pharmaceuticals advisory boards. JM has received grants from Novartis and Chugai to support meeting attendance. All other authors declare no competing interests.
Publisher Copyright:
© 2019 Elsevier Ltd
Copyright:
Copyright 2020 Elsevier B.V., All rights reserved.
PY - 2019/9
Y1 - 2019/9
N2 - Background: 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. Methods: 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. Findings: 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. Interpretation: 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. Funding: GlaxoSmithKline Biologicals SA.
AB - Background: 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. Methods: 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. Findings: 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. Interpretation: 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. Funding: GlaxoSmithKline Biologicals SA.
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U2 - 10.1016/S1473-3099(19)30163-X
DO - 10.1016/S1473-3099(19)30163-X
M3 - Article
C2 - 31399377
AN - SCOPUS:85071373973
SN - 1473-3099
VL - 19
SP - 988
EP - 1000
JO - The Lancet Infectious Diseases
JF - The Lancet Infectious Diseases
IS - 9
ER -
