1. Immunogenicity and safety of the adjuvanted recombinant zoster vaccine in adults with haematological malignancies: a phase 3, randomised, clinical trial and post-hoc efficacy analysis
- Author
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David Pohlreich, Lidia Oostvogels, Mohamed El Idrissi, Alemnew F Dagnew, Jaime Pérez de Oteyza, Maria Belen Navarro Matilla, Dong-Gun Lee, Lars Rombo, Osman Ilhan, Shelly A. McNeil, Aránzazu Alonso Alonso, Po Nan Wang, Anna Johnston, Marta López-Fauqued, Jae Yong Kwak, Raquel Oña Navarrete, Gianluca Gaidano, Javier de la Serna, Ariah Schattner, Philippe Rodon, Ahmed Masood, Teresa del Campo, Bruno Salaun, Terrance Comeau, Andrew Peniket, John Murphy, Boris Afanasyev, Hyeon Seok Eom, Pere Barba Suñol, Sam Milliken, Alessandro Lucchesi, Pierre Zachee, Aleksey Kuvshinov, Seok Jin Kim, Anna Carolina Miranda Castillo, Stella Bowcock, Tzeon Jye Chiou, Stephane Lepretre, Richard Eek, Veli-Jukka Anttila, Faisal Sultan, Sebastian Grosicki, Anne Schuind, Patricia Disperati, Jo Anne H. Young, William Hwang, Thierry Guillaume, Emmanuel Di Paolo, Philippe Quittet, Paul Turner, Dariusz Woszczyk, Dimas Quiel, Norbert Blesing, Naheed Mir, Lucrecia Yáñez San Segundo, Ching Yuan Kuo, Humphrey Pullon, Koen Theunissen, Jae Hoon Lee, Karlis Pauksens, Thomas C. Heineman, Wojciech Homenda, Nikolay Ilyin, Johan Sanmartin Berglund, Dominik Selleslag, Marjatta Sinisalo, Kathleen M. Mullane, Sang Kyun Sohn, Kadir Acar, Albert Kwok Wai Lie, Mickael Aoun, Won Sik Lee, Francesco Zaja, Alexandr Myasnikov, Gabriela Rodriguez Macías, Laura Campora, Je Jung Lee, Olga Samoylova, Peter Van den Steen, Dagnew, A. F., Ilhan, O., Lee, W. -S., Woszczyk, D., Kwak, J. -Y., Bowcock, S., Sohn, S. K., Rodriguez Macias, G., Chiou, T. -J., Quiel, D., Aoun, M., Navarro Matilla, M. B., de la Serna, J., Milliken, S., Murphy, J., Mcneil, S. A., Salaun, B., Di Paolo, E., Campora, L., Lopez-Fauqued, M., El Idrissi, M., Schuind, A., Heineman, T. C., Van den Steen, P., Oostvogels, L., Acar, K., Afanasyev, B., Alonso Alonso, A., Anttila, V. -J., Barba Sunol, P., Blesing, N., Comeau, T., del Campo, T., Disperati, P., Eek, R., Eom, H., Gaidano, G., Grosicki, S., Guillaume, T., Homenda, W., Hwang, W., Ilyin, N., Johnston, A., Kim, S. J., Kuo, C. -Y., Kuvshinov, A., Lee, D. -G., Lee, J. H., Lee, J. -J., Lepretre, S., Lie, A. K. -W., Lucchesi, A., Masood, A., Mir, N., Miranda Castillo, A. C., Mullane, K., Myasnikov, A., Ona Navarrete, R., Pauksens, K., Peniket, A., Perez de Oteyza, J., Pohlreich, D., Pullon, H., Quittet, P., Rodon, P., Rombo, L., Samoylova, O., Sanmartin Berglund, J., Schattner, A., Selleslag, D., Sinisalo, M., Sultan, F., Theunissen, K., Turner, P., Wang, P. -N., Yanez San Segundo, L., Young, J. -A., Zachee, P., and Zaja, F.
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Adult ,Male ,Herpesvirus 3, Human ,medicine.medical_specialty ,Adolescent ,Population ,Antineoplastic Agents ,Antibodies, Viral ,Placebo ,Hematological malignancies ,Immunocompromised Host ,Young Adult ,03 medical and health sciences ,0302 clinical medicine ,Viral Envelope Proteins ,Internal medicine ,medicine ,Herpes Zoster Vaccine ,Humans ,Single-Blind Method ,030212 general & internal medicine ,education ,Adverse effect ,Fatigue ,Immunity, Cellular ,Vaccines, Synthetic ,education.field_of_study ,Vaccines ,Reactogenicity ,H. Zoster ,business.industry ,Immunogenicity ,Middle Aged ,CD4 Lymphocyte Count ,Injection Site Reaction ,Vaccination ,Clinical trial ,Infectious Diseases ,Hematologic Neoplasms ,030220 oncology & carcinogenesis ,Female ,Zoster vaccine ,business ,Vaccine ,medicine.drug - Abstract
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
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- 2019