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Immunocompromised individuals, particularly autologous hematopoietic stem cell transplant (auHSCT) recipients, are at high risk for herpes zoster (HZ). We provide an in-depth description of humoral and cell-mediated immune (CMI) responses by age (protocol-defined) or underlying disease (post-hoc) as well as efficacy by underlying disease (post-hoc) of the adjuvanted recombinant zoster vaccine (RZV) in a randomized observer-blind phase III trial (ZOE-HSCT, NCT01610414). 1846 adult auHSCT recipients were randomized to receive a first dose of either RZV or placebo 50-70 days post-auHSCT, followed by the second dose at 1-2 months (M) later. In cohorts of 114-1721 participants, at 1 M post-second vaccine dose: Anti-gE antibody geometric mean concentrations (GMCs) and median gE-specific CD4[2+] T-cell frequencies (CD4 T cells expressing =2 of four assessed activation markers) were similar between 18-49 and =50-year-olds. Despite lower anti-gE antibody GMCs in non-Hodgkin B-cell lymphoma (NHBCL) patients, CD4[2+] T-cell frequencies were similar between NHBCL and other underlying diseases. The proportion of polyfunctional CD4 T cells increased over time, accounting for 79.6% of gE-specific CD4 T cells at 24 M post-dose two. Vaccine efficacy against HZ ranged between 42.5% and 82.5% across underlying diseases and was statistically significant in NHBCL and multiple myeloma patients. In conclusion, two RZV doses administered early post-auHSCT induced robust, persistent, and polyfunctional gE-specific immune responses. Efficacy against HZ was also high in NHBCL patients despite the lower humoral response.

IMPORTANCE Herpes zoster, a frequent complication following autologous hematopoietic stem cell transplantation (HSCT), is associated with significant morbidity. A nonlive adjuvanted recombinant zoster vaccine has been developed to prevent posttransplantation zoster. OBJECTIVE To assess the efficacy and adverse event profile of the recombinant zoster vaccine in immunocompromised autologous HSCT recipients. DESIGN, SETTING, AND PARTICIPANTS Phase 3, randomized, observer-blinded study conducted in 167 centers in 28 countries between July 13, 2012, and February 1, 2017, among 1846 patients aged 18 years or older who had undergone recent autologous HSCT. INTERVENTIONS Participants were randomized to receive 2 doses of either recombinant zoster vaccine (n=922) or placebo (n=924) administered into the deltoid muscle; the first dose was given 50 to 70 days after transplantation and the second dose 1 to 2 months thereafter. MAIN OUTCOMES AND MEASURES The primary end point was occurrence of confirmed herpes zoster cases. RESULTS Among 1846 autologous HSCT recipients (mean age, 55 years; 688 [37%] women) who received 1 vaccine or placebo dose, 1735 (94%) received a second dose and 1366 (74%) completed the study. During the 21-month median follow-up, at least 1 herpes zoster episode was confirmed in 49 vaccine and 135 placebo recipients (incidence, 30 and 94 per 1000 person-years, respectively), an incidence rate ratio (IRR) of 0.32 (95% CI, 0.22-0.44; P

EgeUn###, Importance: Herpes zoster, a frequent complication following autologous hematopoietic stem cell transplantation (HSCT), is associated with significant morbidity. A nonlive adjuvanted recombinant zoster vaccine has been developed to prevent posttransplantation zoster. Objective: To assess the efficacy and adverse event profile of the recombinant zoster vaccine in immunocompromised autologous HSCT recipients. Design, Setting, and Participants: Phase 3, randomized, observer-blinded study conducted in 167 centers in 28 countries between July 13, 2012, and February 1, 2017, among 1846 patients aged 18 years or older who had undergone recent autologous HSCT. Interventions: Participants were randomized to receive 2 doses of either recombinant zoster vaccine (n = 922) or placebo (n = 924) administered into the deltoid muscle; the first dose was given 50 to 70 days after transplantation and the second dose 1 to 2 months thereafter. Main Outcomes and Measures: The primary end point was occurrence of confirmed herpes zoster cases. Results: Among 1846 autologous HSCT recipients (mean age, 55 years; 688 [37%] women) who received 1 vaccine or placebo dose, 1735 (94%) received a second dose and 1366 (74%) completed the study. During the 21-month median follow-up, at least 1 herpes zoster episode was confirmed in 49 vaccine and 135 placebo recipients (incidence, 30 and 94 per 1000 person-years, respectively), an incidence rate ratio (IRR) of 0.32 (95% CI, 0.22-0.44; P, Cornell University University of Manchester Universitat de València University of Kansas Medical Center, KUMC University of Manchester College of Medicine, Korea University Chonnam National University, CNU North Carolina GlaxoSmithKline Foundation Università degli Studi del Piemonte Orientale, UPO Gilead Sciences Pfizer National Institute of Allergy and Infectious Diseases, NIAID Amgen Merck GlaxoSmithKline foundation, GSK National and Kapodistrian University of Athens Chung Hua University, CHU University of Melbourne Thomas Jefferson University, TJU National Center for Medical Rehabilitation Research, NCMRR Cancer Center, University of Colorado National Cancer Center Helsingin Yliopisto Hacettepe Üniversitesi Tufts Medical Center City, University of London, City Gachon University Chung Hua University, CHU Uniwersytet Jagiellonski Collegium Medicum Manchester Biomedical Research Centre, BRC China Medical University Hospital, CMUH Chonbuk National University Hospital Seoul National University Hospital, SNUH Universitair Medisch Centrum Utrecht, UMC Universiti Kebangsaan Malaysia University of Seoul, UOS University of Minnesota, UM Ankara Universitesi Cleveland Clinic Foundation, CCF City, University of London, City University of North Carolina at Chapel Hill, UNC-CH Kyungpook National University, KNU, Author Affiliations: GlaxoSmithKline, Wavre, Belgium (Bastidas, Campora, Lopez-Fauqued); Hospital Universitario 12 de Octubre, Madrid, Spain (de la Serna); GlaxoSmithKline, Rixensart, Belgium (El Idrissi); CureVac AG, Tübingen, Germany (Oostvogels); University Hospital of Montpellier, Montpellier, France (Quittet); Hospital Ramón y Cajal, Madrid, Spain (López-Jiménez); Ege University Medical School, Izmir, Turkey (Vural); Charles University Hospital, Prague, Czech Republic (Pohlreich); Rambam Health Care Campus, Haifa, Israel (Zuckerman); Brigham and Women’s Hospital/Dana-Farber Cancer Institute, Boston, Massachusetts (Issa); Department of Translational Medicine, University of Eastern Piedmont, Novara, Italy (Gaidano); Chonnam National University Hwasun Hospital, Jellanamdo, Republic of Korea (J.-J. Lee); University of Kansas Cancer Center, Westwood (Abhyankar); Hospital Clínico Universitario, School of Medicine, University of Valencia, Valencia, Spain (Solano); Centro Integral Oncológico Clara Campal (CIOCC), Universidad CEU San Pablo, Madrid, Spain (Perez de Oteyza); Weill Medical College of Cornell University, New York, New York (Satlin); Department of Hematology and Oncology, Charité University Medical Center, Berlin, Germany (Schwartz); Preventive Medicine and Epidemiology Department, University Hospital Vall d’Hebron, Barcelona, Spain (Campins); Haematology Department, Manchester University NHS Foundation Trust, Manchester Royal Infirmary, Manchester, England (Rocci); Faculty of Biology, Medicine and Health, School of Medical Science, Division of Cancer Sciences, University of Manchester, Manchester, England (Rocci); Hospital de Donostia, San Sebastián, Spain (Vallejo Llamas); Department of Internal Medicine, Seoul St Mary’s Hospital, College of Medicine, Catholic University of Korea, Seoul, South Korea (D.-G. Lee); Hospital Ampang, Selangor, Malaysia (Tan); Royal Hobart Hospital, Hobart, Australia (Johnston); Department of Clinical Haematology, Austin Health, Heidelberg, Australia (Grigg); Fred Hutchinson Cancer Research Center, Seattle, Washington (Boeckh); Halozyme Therapeutics, San Diego, California (Heineman); University of Pennsylvania, Philadelphia (Stadtmauer); Duke University Medical Center, Durham, North Carolina (Sullivan). -- reported being employed by and holding stock options in GlaxoSmithKline (GSK). Dr El Idrissi reported being employed by and holding stock options in GSK. Dr Oostvogels reported being employed by GSK during conception and/or conduct of the study and being currently employed by CureVac AG; being an inventor on a patent owned by GSK relevant to recombinant zoster vaccine; and holding stock in GSK. Dr López-Jiménez reported receipt of grants from Hospital Ramon y Cajal. Dr Vural reported receipt of grants and personal fees from GSK. Dr Issa reported receipt of grants from GSK, Merck, and Astellas and personal fees from Akros Pharma. Dr Gaidano reported receipt of trial patient fees from GSK and personal fees from Abbvie, Roche, Gilead, Janssen, and Morphosys. Dr Perez de Oteyza reported receipt of grants from GSK, Pharmacyclics, Vivia-Biotech, Morphosys, and Helsinn; grants and personal fees from Roche, Janssen, Takeda, and Celgene; and personal fees from Servier and Gilead. Dr Satlin reported receipt of grants from GSK, Allergan, Merck, Biofire Diagnostics, and Biomerieux and consulting fees from Achaogen and Shionogi. Dr Schwartz reported receipt of grants from GSK and personal fees and nonfinancial support from Amgen, Basilea Pharmaceutica, Gilead, Jazz Pharmaceuticals, Merck Sharp & Dohme, and Pfizer. Dr Campins reported receipt of grants and personal fees from GSK; participation as an investigator in clinical trials from GSK and Novartis; and participation in expert meetings and symposiums organized by Pfizer, GSK, Sanofi-Pasteur, Merck Sharp & Dohme, and Novartis. Dr Rocci reported receipt of consultancy fees from Takeda and Sanofi and honoraria from Takeda, Celgene, Novartis, Amgen, and Janssen and advisory board membership for Novartis, Amgen, and Janssen. Dr Johnston reported receipt of personal fees from Roche, Janssen Cilag, Celgene, and Merck Sharp & Dohme. Dr Grigg reports advisory board membership for Novartis, Gilead, Roche, Merck Sharp & Dohme, Takeda, and Bristol-Myers Squibb. Dr Boeckh reported receipt of grants and personal fees from GSK, Merck, and Chimerix and personal fees from Clinigen. Dr Campora reported being an employee of GSK; owning shares in GSK; and receipt of personal fees from GSK. Dr Lopez-Fauqued reported being an employee of GSK. Dr Heineman reported being an employee of GSK during conception and/or conduct of the study; holding stock and stock options in GSK; being an inventor on a patent owned by GSK relevant to recombinant zoster vaccine; being a paid consultant for GSK. Dr Stadtmauer reported receipt of grants from GSK. Dr Sullivan reported receipt of grants and personal fees from GSK; personal fees from Kiadis Pharmaceutical and Roche Genentech; and a grant from the National Institute of Allergy and Infectious Diseases awarded to his university. No other disclosures were reported. -- (Hematology Department, National and Kapodistrian University of Athens, “Laikon” General Hospital, Athens, Greece), Veli-Jukka Anttila, MD, PhD (Inflammation Center, University of Helsinki and Helsinki University Hospital, Helsinki, Finland), Mickael Aoun, MD (Microbiologie Infectious Diseases, Institut Jules Bordet, Bruxelles, Belgium), Ibrahim Barista, MD (Hacettepe University Medical Faculty, Ankara, Turkey), Leanne Berkahn, MB, ChB (Department of Heamatology, Auckland City Hospital, Grafton, New Zealand), Adrian J. C. Bloor, PhD, FRCP (Haematology and Transplant Unit, Christie NHS Foundation Trust, Manchester, England), Raewyn Broady, MB, ChB (Vancouver General Hospital, Vancouver, British Columbia, Canada), Peter Brossart, MD (Universitaetsklinikum Bonn, Bonn, Germany), Francis K. Buadi, MB, ChB (Mayo Clinic, Rochester, Minnesota), Claude-Eric Bulabois, MD (Service d’Hématologie, CHU de Grenoble–Hôpital Michallon, Grenoble, France), Guy Cantin, MD (CHU de Quebec–Hopital de l’Enfant-Jesus, Quebec City, Quebec, Canada), Claudia Cellini, MD (UO di Ematologia, Ospedale Santa Maria delle Croci, Ravenna, Italy), Pranatharthi Haran Chandrasekar, MD (Karmanos Cancer Institute, Detroit, Michigan), Thomas Chauncey, MD (Veterans Administration Puget Sound Health Care System, Seattle, Washington), Antonio Cuneo, MD (Unità Operativa di Ematologia, Azienda Ospedale Universitaria Arcispedale S. Anna, Venice, Italy), Sanjeet Singh Dadwal, MD (City of Hope National Medical Center, Duarte, California) , Michael Dickinson, MBBS(hons), DMedSci, FRACP, FRCPA (Clinical Haematology, Peter MacCallum Cancer Centre and Royal Melbourne Hospital, and Sir Peter MacCallum Department of Oncology, University of Melbourne, Melbourne, Australia), HyeonSeok Eom, MD, PhD (National Cancer Center, Kyunggi-do, Korea), Albert Esquirol Sanfeliu, MD (Hospital Santa Creu i Sant Pau, Barcelona, Spain), Christelle Ferra Coll, MD, PhD (Hospital Germans Trias i Pujol, Barcelona, Spain), Phyllis R. Flomenberg, MD (Kimmel Cancer Center, Thomas Jefferson University, Philadelphia, Pennsylvania), Ana Pilar González-Rodríguez, MD, PhD (Hospital Central de Asturias, Oviedo, Spain), David J. Gottlieb, MD (Department of Haematology, Westmead Hospital, Westmead, Australia), Sigal Grisariu, MD (Hadassah Medical Center, Jerusalem, Israel), Andreas Guenther, MD (Universitaetsklinikum Schleswig-Holstein, Kiel, Germany), Jonathan Gutman, MD (University of Colorado Cancer Center, Aurora), Uwe Hahn, MD (Department of Haematology and Oncology, Queen Elizabeth Hospital, Woodville, Australia), Werner J. Heinz, MD (Universitaetsklinikum Wuerzburg, Wuerzburg, Germany), Inmaculada Heras, MD, PhD (Hospital General Universitario J. M. Morales Meseguer, Murcia, Spain), Takashi Ikeda, MD, PhD (Shizuoka Cancer Center, Shizuoka, Japan), Isidro Jarque, MD, PhD (Hospital Universitario y Politécnico La Fe, Valencia, Spain), Meinolf Karthaus, MD (Staedtisches Krankenhaus Muenchen, Muenchen, Germany), Tessa Kerre, MD, PhD (Hematologie, UZ Gent, Gent, Belgium), Alexander Kiani, MD (Klinikum Bayreuth, Bayreuth, Germany), Andreas K. Klein, MD (Tufts Medical Center, Boston, Massachusetts), Grzegorz Kofla, MD (Charite, Berlin, Germany), Irina V. Kryuchkova, MD, PhD (Research Institute of Clinical Immunology, Novosibirsk, Russia), Ching-Yuan Kuo, MD (Chang Gung Memorial Hospital–Kaoshiung, Kaohsiung, Taiwan), John Kuruvilla, MD (Princess -- Margaret Hospital, Toronto, Ontario, Canada), Aleksey Kuvshinov (Russian Hematology and Transfusiology Research Center, St Petersburg, Russia), Jae-Yong Kwak, MD, PhD (Chonbuk National University Hospital, Jeonju, South Korea), Jae Hoon Lee, MD, PhD (Hematology, Gachon University Gil Hospital, Incheon, South Korea), Stéphane Lepretre, MD (Département d’Hématologie, Centre Henri Becquerel, Rouen, France), Albert Kwok-Wai Lie, MBBS (Division of Hematology/Oncology and Bone Marrow Transplantation, Department of Medicine, Queen Mary Hospital, Hong Kong, China), Alessandro Lucchesi, MD (Oncologia Medica, Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori IRCCS, Meldola, Italy), Johan Maertens, MD, PhD (Hematologie, UZ Leuven–Campus Gasthuisberg, Leuven, Belgium), Erik W. A. Marijt, MD, PhD (Leids UMC, Leiden, Netherlands), Carmen Martínez Muñoz, MD (Hospital Clinic i Provincial, Barcelona, Spain), Mariagrazia Michieli, MD (UOS Dipartimento Terapia Cellulare-Chemioter Alte Dosi, Centro di Riferimento Oncologico IRCCS, Aviano, Italy), Samuel T. Milliken, MBBS (Department of Haematology, St Vincent’s Hospital, Darlinghurst, Australia), Noël Milpied, MD (Hématologie Clinique et Thérapie Cellulaire, CHU de Bordeaux–Hôpital du Haut Lévêque, Pessac, France), Jorge Monserrat Coll, MD (Hospital Virgen de la Arrixaca, Murcia, Spain), Sherif Beniameen Mossad, MD (Department of Infectious Diseases, Cleveland Clinic Foundation, Cleveland, Ohio), John Murphy, MB, ChB (Monklands Hospital, Airdrie, Scotland), María Belén Navarro Matilla, MD (Hospital Puerta de Hierro, Madrid, Spain), Jan Novak, MD, PhD (Oddeleni Klinicke Hematologie, Fakultni Nemocnice Kralovske Vinohrady, Prague, Czech Republic), Harold J. Olney, MD, CM (Centre Hospitalier de l’Universite de Montreal, Montreal, Quebec, Canada), Raquel Oña Navarrete, MD, PhD (M. D. Anderson, Madrid, Spain), María Jesús Pascual Cascón, MD (Hospital Carlos Haya, Málaga, Spain), Andy Peniket (Oxford University Biomedical Research Centre, Oxford, England), Ganeva Penka (CTH Sofia, Sofia, Bulgaria), Beata Piatkowska-Jakubas, DSc, MD (Department of Haematology, Jagiellonian University Medical College, Krakow, Poland), Marta Polo Zarzuela, MD (Hospital Clínico San Carlos, Madrid, Spain), Dimas Quiel, MD (Complejo Hospitalario Dr Arnulfo Arias Madrid, Panama City, Panama), Scott D. Rowley, MD, FACP (John Theuer Cancer Center, Hackensack University Medical Center, Hackensack, New Jersey), Waleed Sabry, MD, MSc, PhD (Saskatoon Cancer Centre, Saskatoon, Saskatchewan, Canada), Tommi Mikael Salmi, MD (Sisatautien Klinikka, Hematologian Yksikko os 015, Turun Yliopistollinen Keskussairaala, Turku, Finland), Dominik L. D. Selleslag, MD (Hematologie, AZ Sint-Jan Brugge– Oostende AV–Campus Sint-Jan, Brugge, Belgium), Thomas C. Shea, MD (Division of Hematology and Medical Oncology, University of North Carolina at Chapel Hill), Gerda Silling, MD (Universitaetsklinikum Muenster, Muenster, Germany), Ulla Marjatta Sinisalo, MD, PhD (Hematology Unit, Department of Internal Medicine, Tampere University Hospital, Tampere, Finland), Sang Kyun Sohn, MD, PhD (School of Medicine, Kyungpook National University, Daegu, South Korea), Peter Staib, MD, PhD (St Antonius Hospital, Eschweiler, Germany), Jeff Szer, MBBS (Haematology Department, Royal Melbourne Hospital, Parkville, Australia), Koen Theunissen, MD (Hematologie, Jessa Ziekenhuis–Campus Virga Jesse, Hasselt, Belgium), Pervin Topcuoglu, MD (Ankara University, Ankara, Turkey), Natalya G. Tyurina, PhD (Moscow Oncology Reserach Institute NA Herzen, Moscow, Russia), Mikhail Uvarov, MD, PhD (City Clinical Hospital No. 31, St Petersburg, Russia), Fadilah S. Abdul Wahid, PhD (Department of Medicine, Universiti Kebangsaan Malaysia Medical Center, Kuala Lumpur, Malaysia), Lucrecia Yáñez San Segundo, MD, PhD (Hospital Marqués de Valdecilla, Santander, Spain), Zeynep Arzu Yegin (Gazi University Medical Faculty, Ankara, Turkey), Su-Peng Yeh, MD (Department of Hematology, China Medical University Hospital, Taichung, Taiwan), Sze-Fai Yip, MD (Department of Medicine and Geriatrics, Tuen Mun Hospital, Tuen Mun, Hong Kong), Sung Soo Yoon, MD, PhD (Seoul National University Hospital, Seoul, South Korea), Jo-Anne H. Young, MD (University of Minnesota, Minneapolis), Pierre Zachée, MD, PhD (Hematologie-Oncologie, Ziekenhuisnetwerk Antwerpen, ZNA Stuivenberg and ZNA Middelheim, Antwerpen, Belgium), Francesco Zaja, MD (Clinica Ematologica, Azienda Ospedaliero Universitaria S. Maria Misericordia, Udine, Italy). Principal investigators and study sites are listed in eTable 9 and committees and GSK team members are listed in the eBox in Supplement 3. -- --

Introduction Peripheral T-cell lymphoma (PTCL) is a rare and heterogeneous group of diseases associated with poor prognosis, representing 10-15% of non-Hodgkin lymphomas. Although CHOP (cyclophosphamide, doxorubicin, vincristine, and prednisone) or CHOP-like regimens are often preferred as 1st line treatment, the treatment outcome is poor with 5-year overall survival (OS) rate of 30-40%. In an effort to improve the survival outcomes of these patients, autologous hematopoietic stem cell transplantation (ASCT) as an upfront consolidative treatment has been proposed for patients achieving partial or complete remission after induction therapy. However, the role of ASCT still remains undefined since no randomized trials have demonstrated survival benefit of ASCT in this setting. To better understand the clinical characteristics, treatment patterns, and outcomes in patients with PTCL, we have conducted a nationwide, multicenter, prospective registry study for newly diagnosed patients with PTCL. Methods Patients with PTCL receiving chemotherapy with curative intent were registered and prospectively monitored (ClinicalTrials.gov, no. NCT02364466). All patients were pathologically diagnosed with PTCL according to the 2008 World Health Organization classification of lymphoid neoplasms. Extranodal NK/T cell lymphoma, cutaneous T cell lymphoma, Mycosis fungoides and Sezary syndrome were excluded. The target number for enrollment was 200, and an interim analysis was previously reported at the time of enrollment of 155 patients (ASH 2017). An updated analysis of 198 patients was performed. Results The median age was 59 years (range, 49-70), 122 patients (61.6%) were male and 168 (84.9%) had ECOG performance status of 0-1. PTCL, not otherwise specified was the most common pathologic subtype (n = 80, 40.4%), followed by angioimmunoblastic T cell lymphoma (n = 60, 30.3%). The most frequently administered 1st line regimen was CHOP or CHOP-like regimen (n = 165, 83.3%), followed by ICE (ifosfamide, carboplatin, and etoposide) or ICE-like regimen (n = 23, 11.6%), and others (n = 10, 5.1%). With a median follow-up duration of 28.2 months (95% CI, 25.6-30.6), 2-yr progression-free survival (PFS) rate was 44.4% (95% CI, 37.5-57.4) and 2-yr OS rate was 64.4% (95% CI, 57.4-72.1). Response evaluation for 1st line regimens were available in 175 patients. Among these patients, there was no significant difference in overall response rate (ORR) and complete response (CR) rate between patients treated with CHOP or CHOP-like vs. ICE or ICE-like regimen (ORR: 73.6 vs. 72.7%, P = 1.000; CR rate: 58.1% vs. 45.5%, P = 0.375). In addition, no significant difference was observed regarding PFS and OS between the two treatment groups (CHOP or CHOP-like vs. ICE or ICE-like; 2-yr PFS rate: 45.2 vs. 38.3%, P = 0.39; 2-year OS rate: 65.7 vs. 50.7% P = 0.43) (Figure 1A, B). Among 121 patients younger than 65 years of age who are eligible for transplantation, autologous hematopoietic stem cell transplantation (ASCT) was performed as an upfront consolidative treatment in 51 patients (42.1%). Patients who received upfront ASCT was associated with significantly better PFS and OS compared with patients who did not, with a 2-yr PFS rate of 52.3 vs. 37.0% (P = 0.032) and 2-yr OS rate of 74.2 vs. 57.1% (P = 0.028), respectively (Figure 2A, B). A total of 81 patients were treated with 2nd line chemotherapy for refractory or relapsed disease, and response evaluation for 2nd line chemotherapy was available in 63 patients. Among these patients ORR and CR rate were 49.2% and 30.2%, respectively. Conclusion Our study demonstrated that survival outcome with current treatment options for patients with PTCL remains poor. Although CHOP or CHOP-like regimens were the most commonly used 1st line regimens, no survival benefit was observed when compared with ICE or ICE-like regimens, suggesting that more efforts are needed to establish a standard 1st line treatment for PTCL. ASCT may provide survival benefit in transplant eligible patients, which warrants further evaluation in randomized controlled trials. Disclosures Yoon: Janssen: Consultancy; MSD: Consultancy; Novartis: Consultancy, Honoraria; Yuhan Pharma: Research Funding; Amgen: Consultancy, Honoraria; Genentech, Inc.: Research Funding; Kyowa Hako Kirin: Research Funding. Kim:F. Hoffmann-La Roche Ltd: Research Funding; Celltrion: Research Funding; Novartis: Research Funding; Donga: Research Funding; Kyowa-Kirin: Research Funding; Novartis: Research Funding; J + J: Research Funding.