Cargando…

Timing and Immune Status after Cellular Therapies Predict Response to COVID-19 Vaccines

BACKGROUND Cellular therapies (allogeneic hematopoietic cell transplantation, allo-HCT, autologous hematopoietic cell transplantation, auto-HCT, and chimeric antigen receptor T cell therapy, CAR T) render patients severely immunocompromised for extended periods post-therapy. Emerging data suggest re...

Descripción completa

Detalles Bibliográficos
Autores principales: Tamari, Roni, Politikos, Ioannis, Knorr, David, Vardhana, Santosha, Young, Jennifer, Marcello, Leeann, Doddi, Sital, Devlin, Sean M, Ramanathan, Lakshmi, Pessin, Melissa S., Dunn, Erica, Palazzo, Meighan A., Bravo, Christina, Papanicolaou, Genovefa A., Kamboj, Mini, Perales, Miguel-Angel, Chung, David J., Shah, Gunjan L
Formato: Online Artículo Texto
Lenguaje:English
Publicado: American Society of Hematology. Published by Elsevier Inc. 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8701592/
http://dx.doi.org/10.1182/blood-2021-151376
_version_ 1784621039349661696
author Tamari, Roni
Politikos, Ioannis
Knorr, David
Vardhana, Santosha
Young, Jennifer
Marcello, Leeann
Doddi, Sital
Devlin, Sean M
Ramanathan, Lakshmi
Pessin, Melissa S.
Dunn, Erica
Palazzo, Meighan A.
Bravo, Christina
Papanicolaou, Genovefa A.
Kamboj, Mini
Perales, Miguel-Angel
Chung, David J.
Shah, Gunjan L
author_facet Tamari, Roni
Politikos, Ioannis
Knorr, David
Vardhana, Santosha
Young, Jennifer
Marcello, Leeann
Doddi, Sital
Devlin, Sean M
Ramanathan, Lakshmi
Pessin, Melissa S.
Dunn, Erica
Palazzo, Meighan A.
Bravo, Christina
Papanicolaou, Genovefa A.
Kamboj, Mini
Perales, Miguel-Angel
Chung, David J.
Shah, Gunjan L
author_sort Tamari, Roni
collection PubMed
description BACKGROUND Cellular therapies (allogeneic hematopoietic cell transplantation, allo-HCT, autologous hematopoietic cell transplantation, auto-HCT, and chimeric antigen receptor T cell therapy, CAR T) render patients severely immunocompromised for extended periods post-therapy. Emerging data suggest reduced immune responses to COVID-19 vaccines among patients with hematologic malignancies, but data for cellular therapy recipients are sparse. We therefore assessed immune responses to mRNA COVID-19 vaccines among patients who underwent cellular therapies at our center to identify predictors of response. PATIENT AND METHODS In this observational prospective study, anti-SARS-CoV-2 spike IgG antibody titers and circulating neutralizing antibodies were measured at 1 and 3 months after the 1 (st) dose of vaccination. CD4, CD19, mitogen, and IgG levels from patient samples collected prior to initiation of vaccination in a subset of patients were used to assess immune recovery and association with response. A concurrent healthy donor (HD) cohort provided control response rates. RESULTS Allo-HCT (N=149), auto HCT (N=61), and CAR T (N=7) patients vaccinated between 12/22/2020- 2/28/2021 with mRNA vaccines and 69 HD participated in this study. At 3 months, 188 pts (87%) had a positive anti-SARS-CoV-2 spike IgG levels (median 5,379 AU/mL, IQR 451-15,750), and 139 (77%) had a positive neutralization Ab assay (median 93%, IQR 36-96%). All HD (100%) had a positive anti-SARS-CoV-2 spike IgG and a positive neutralization Ab assay with median levels of 8,011 AU/mL (IQR 4573-11,159) and 96% (IQR 78- 96%), respectively. Time from vaccination to cellular therapy was associated with response; 67% of patients vaccinated in the first 12 months post-cellular therapy (N=42) mounted a serologic response, compared with patients vaccinated between 12-24 (89%) (N=45), 24-36 (91%) (N=32) and >36 (93%) (N=98) months post-treatment, p= 0.001 (figure 1). Patients with immune parameters below the recommended threshold for vaccinations post-cellular therapies were also less likely to mount a response (figure 2): CD4+ T-cell count < 200 vs >200 cells/μL, 66% vs 87% (p=0.012); CD19+ B-cell count <50 vs >50 cells/μL; 33% vs 95% (p<0.001), phytohemagglutinin mitogen response <40% vs >40%, 42% vs 89% (p<0.001), and IgG <500 vs >500 mg/dl, 71% vs 91% (p=0.003). Patient age, gender, prior COVID-19 infection, treatment with IVIG, and type of mRNA COVID-19 vaccine were not associated with the likelihood of serologic response. CONCLUSION This largest cohort to date, demonstrates that COVID-19 vaccine responses of cellular therapy recipients are reduced compared to healthy control and response varies based on time interval from cellular therapy and immune function at the time of vaccination, underscoring the importance of monitoring immune status parameters, as well as qualitative measures (neutralizing Ab) of vaccine response, in informing clinical decisions, including the indication for booster vaccines. [Figure: see text] DISCLOSURES: Politikos:  Merck: Research Funding; ExcellThera, Inc: Other: Member of DSMB - Uncompensated. Vardhana:  Immunai: Membership on an entity's Board of Directors or advisory committees. Perales:  Equilium: Honoraria; Cidara: Honoraria; Sellas Life Sciences: Honoraria; Miltenyi Biotec: Honoraria, Other; Celgene: Honoraria; MorphoSys: Honoraria; Takeda: Honoraria; Incyte: Honoraria, Other; Karyopharm: Honoraria; Kite/Gilead: Honoraria, Other; Merck: Honoraria; NexImmune: Honoraria; Novartis: Honoraria, Other; Medigene: Honoraria; Omeros: Honoraria; Servier: Honoraria; Bristol-Myers Squibb: Honoraria; Nektar Therapeutics: Honoraria, Other. Shah:  Amgen: Research Funding; Janssen Pharmaceutica: Research Funding.
format Online
Article
Text
id pubmed-8701592
institution National Center for Biotechnology Information
language English
publishDate 2021
publisher American Society of Hematology. Published by Elsevier Inc.
record_format MEDLINE/PubMed
spelling pubmed-87015922021-12-28 Timing and Immune Status after Cellular Therapies Predict Response to COVID-19 Vaccines Tamari, Roni Politikos, Ioannis Knorr, David Vardhana, Santosha Young, Jennifer Marcello, Leeann Doddi, Sital Devlin, Sean M Ramanathan, Lakshmi Pessin, Melissa S. Dunn, Erica Palazzo, Meighan A. Bravo, Christina Papanicolaou, Genovefa A. Kamboj, Mini Perales, Miguel-Angel Chung, David J. Shah, Gunjan L Blood 722.Allogeneic Transplantation: Acute and Chronic GVHD, Immune Reconstitution BACKGROUND Cellular therapies (allogeneic hematopoietic cell transplantation, allo-HCT, autologous hematopoietic cell transplantation, auto-HCT, and chimeric antigen receptor T cell therapy, CAR T) render patients severely immunocompromised for extended periods post-therapy. Emerging data suggest reduced immune responses to COVID-19 vaccines among patients with hematologic malignancies, but data for cellular therapy recipients are sparse. We therefore assessed immune responses to mRNA COVID-19 vaccines among patients who underwent cellular therapies at our center to identify predictors of response. PATIENT AND METHODS In this observational prospective study, anti-SARS-CoV-2 spike IgG antibody titers and circulating neutralizing antibodies were measured at 1 and 3 months after the 1 (st) dose of vaccination. CD4, CD19, mitogen, and IgG levels from patient samples collected prior to initiation of vaccination in a subset of patients were used to assess immune recovery and association with response. A concurrent healthy donor (HD) cohort provided control response rates. RESULTS Allo-HCT (N=149), auto HCT (N=61), and CAR T (N=7) patients vaccinated between 12/22/2020- 2/28/2021 with mRNA vaccines and 69 HD participated in this study. At 3 months, 188 pts (87%) had a positive anti-SARS-CoV-2 spike IgG levels (median 5,379 AU/mL, IQR 451-15,750), and 139 (77%) had a positive neutralization Ab assay (median 93%, IQR 36-96%). All HD (100%) had a positive anti-SARS-CoV-2 spike IgG and a positive neutralization Ab assay with median levels of 8,011 AU/mL (IQR 4573-11,159) and 96% (IQR 78- 96%), respectively. Time from vaccination to cellular therapy was associated with response; 67% of patients vaccinated in the first 12 months post-cellular therapy (N=42) mounted a serologic response, compared with patients vaccinated between 12-24 (89%) (N=45), 24-36 (91%) (N=32) and >36 (93%) (N=98) months post-treatment, p= 0.001 (figure 1). Patients with immune parameters below the recommended threshold for vaccinations post-cellular therapies were also less likely to mount a response (figure 2): CD4+ T-cell count < 200 vs >200 cells/μL, 66% vs 87% (p=0.012); CD19+ B-cell count <50 vs >50 cells/μL; 33% vs 95% (p<0.001), phytohemagglutinin mitogen response <40% vs >40%, 42% vs 89% (p<0.001), and IgG <500 vs >500 mg/dl, 71% vs 91% (p=0.003). Patient age, gender, prior COVID-19 infection, treatment with IVIG, and type of mRNA COVID-19 vaccine were not associated with the likelihood of serologic response. CONCLUSION This largest cohort to date, demonstrates that COVID-19 vaccine responses of cellular therapy recipients are reduced compared to healthy control and response varies based on time interval from cellular therapy and immune function at the time of vaccination, underscoring the importance of monitoring immune status parameters, as well as qualitative measures (neutralizing Ab) of vaccine response, in informing clinical decisions, including the indication for booster vaccines. [Figure: see text] DISCLOSURES: Politikos:  Merck: Research Funding; ExcellThera, Inc: Other: Member of DSMB - Uncompensated. Vardhana:  Immunai: Membership on an entity's Board of Directors or advisory committees. Perales:  Equilium: Honoraria; Cidara: Honoraria; Sellas Life Sciences: Honoraria; Miltenyi Biotec: Honoraria, Other; Celgene: Honoraria; MorphoSys: Honoraria; Takeda: Honoraria; Incyte: Honoraria, Other; Karyopharm: Honoraria; Kite/Gilead: Honoraria, Other; Merck: Honoraria; NexImmune: Honoraria; Novartis: Honoraria, Other; Medigene: Honoraria; Omeros: Honoraria; Servier: Honoraria; Bristol-Myers Squibb: Honoraria; Nektar Therapeutics: Honoraria, Other. Shah:  Amgen: Research Funding; Janssen Pharmaceutica: Research Funding. American Society of Hematology. Published by Elsevier Inc. 2021-11-23 2021-12-24 /pmc/articles/PMC8701592/ http://dx.doi.org/10.1182/blood-2021-151376 Text en Copyright © 2021 American Society of Hematology. Published by Elsevier Inc. All rights reserved. Since January 2020 Elsevier has created a COVID-19 resource centre with free information in English and Mandarin on the novel coronavirus COVID-19. The COVID-19 resource centre is hosted on Elsevier Connect, the company's public news and information website. Elsevier hereby grants permission to make all its COVID-19-related research that is available on the COVID-19 resource centre - including this research content - immediately available in PubMed Central and other publicly funded repositories, such as the WHO COVID database with rights for unrestricted research re-use and analyses in any form or by any means with acknowledgement of the original source. These permissions are granted for free by Elsevier for as long as the COVID-19 resource centre remains active.
spellingShingle 722.Allogeneic Transplantation: Acute and Chronic GVHD, Immune Reconstitution
Tamari, Roni
Politikos, Ioannis
Knorr, David
Vardhana, Santosha
Young, Jennifer
Marcello, Leeann
Doddi, Sital
Devlin, Sean M
Ramanathan, Lakshmi
Pessin, Melissa S.
Dunn, Erica
Palazzo, Meighan A.
Bravo, Christina
Papanicolaou, Genovefa A.
Kamboj, Mini
Perales, Miguel-Angel
Chung, David J.
Shah, Gunjan L
Timing and Immune Status after Cellular Therapies Predict Response to COVID-19 Vaccines
title Timing and Immune Status after Cellular Therapies Predict Response to COVID-19 Vaccines
title_full Timing and Immune Status after Cellular Therapies Predict Response to COVID-19 Vaccines
title_fullStr Timing and Immune Status after Cellular Therapies Predict Response to COVID-19 Vaccines
title_full_unstemmed Timing and Immune Status after Cellular Therapies Predict Response to COVID-19 Vaccines
title_short Timing and Immune Status after Cellular Therapies Predict Response to COVID-19 Vaccines
title_sort timing and immune status after cellular therapies predict response to covid-19 vaccines
topic 722.Allogeneic Transplantation: Acute and Chronic GVHD, Immune Reconstitution
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8701592/
http://dx.doi.org/10.1182/blood-2021-151376
work_keys_str_mv AT tamarironi timingandimmunestatusaftercellulartherapiespredictresponsetocovid19vaccines
AT politikosioannis timingandimmunestatusaftercellulartherapiespredictresponsetocovid19vaccines
AT knorrdavid timingandimmunestatusaftercellulartherapiespredictresponsetocovid19vaccines
AT vardhanasantosha timingandimmunestatusaftercellulartherapiespredictresponsetocovid19vaccines
AT youngjennifer timingandimmunestatusaftercellulartherapiespredictresponsetocovid19vaccines
AT marcelloleeann timingandimmunestatusaftercellulartherapiespredictresponsetocovid19vaccines
AT doddisital timingandimmunestatusaftercellulartherapiespredictresponsetocovid19vaccines
AT devlinseanm timingandimmunestatusaftercellulartherapiespredictresponsetocovid19vaccines
AT ramanathanlakshmi timingandimmunestatusaftercellulartherapiespredictresponsetocovid19vaccines
AT pessinmelissas timingandimmunestatusaftercellulartherapiespredictresponsetocovid19vaccines
AT dunnerica timingandimmunestatusaftercellulartherapiespredictresponsetocovid19vaccines
AT palazzomeighana timingandimmunestatusaftercellulartherapiespredictresponsetocovid19vaccines
AT bravochristina timingandimmunestatusaftercellulartherapiespredictresponsetocovid19vaccines
AT papanicolaougenovefaa timingandimmunestatusaftercellulartherapiespredictresponsetocovid19vaccines
AT kambojmini timingandimmunestatusaftercellulartherapiespredictresponsetocovid19vaccines
AT peralesmiguelangel timingandimmunestatusaftercellulartherapiespredictresponsetocovid19vaccines
AT chungdavidj timingandimmunestatusaftercellulartherapiespredictresponsetocovid19vaccines
AT shahgunjanl timingandimmunestatusaftercellulartherapiespredictresponsetocovid19vaccines