SARS-CoV-2 vaccination in the first year after hematopoietic cell transplant or chimeric antigen receptor T cell therapy: A prospective, multicenter, observational study (BMT CTN 2101)

Joshua A Hill; Michael J Martens; Jo-Anne H Young; Kavita Bhavsar; Jianqun Kou; Min Chen; Lik Wee Lee; Aliyah Baluch; Madhav V Dhodapkar; Ryotaro Nakamura; Kristin Peyton; Dianna S Howard; Uroosa Ibrahim; Zainab Shahid; Paul Armistead; Peter Westervelt; John McCarty; Joseph McGuirk; Mehdi Hamadani; Susan DeWolf; Kinga Hosszu; Elad Sharon; Ashley Spahn; Amir A Toor; Stephanie Waldvogel; Lee M Greenberger; Jeffery J Auletta; Mary M Horowitz; Marcie L Riches; Miguel-Angel Perales

doi:10.1101/2024.01.24.24301058

SARS-CoV-2 vaccination in the first year after hematopoietic cell transplant or chimeric antigen receptor T cell therapy: A prospective, multicenter, observational study (BMT CTN 2101)

medRxiv [Preprint]. 2024 Jan 25:2024.01.24.24301058. doi: 10.1101/2024.01.24.24301058.

Authors

Joshua A Hill¹, Michael J Martens^{2

3}, Jo-Anne H Young⁴, Kavita Bhavsar², Jianqun Kou², Min Chen², Lik Wee Lee⁵, Aliyah Baluch⁶, Madhav V Dhodapkar⁷, Ryotaro Nakamura⁸, Kristin Peyton⁹, Dianna S Howard¹⁰, Uroosa Ibrahim¹¹, Zainab Shahid¹², Paul Armistead¹³, Peter Westervelt¹⁴, John McCarty¹⁵, Joseph McGuirk¹⁶, Mehdi Hamadani¹⁷, Susan DeWolf¹², Kinga Hosszu¹², Elad Sharon¹⁸, Ashley Spahn¹⁹, Amir A Toor²⁰, Stephanie Waldvogel¹⁹, Lee M Greenberger²¹, Jeffery J Auletta^{19

22}, Mary M Horowitz², Marcie L Riches², Miguel-Angel Perales^{12

23}

Affiliations

¹ Vaccine and Infectious Disease, Fred Hutchinson Cancer Center, and Department of Medicine, University of Washington, Seattle, WA, USA.
² Center for International Blood and Marrow Transplantation Research, Medical College of Wisconsin, Milwaukee, WI, USA.
³ Division of Biostatistics, Medical College of Wisconsin, Milwaukee, WI, USA.
⁴ University of Minnesota, Minneapolis, MN, USA.
⁵ Adaptive Biotechnologies Corp, Seattle, WA, USA.
⁶ H. Lee Moffitt Cancer Center and Research Institute, Tampa, FL, USA.
⁷ Emory University - School of Medicine, Atlanta, GA, USA.
⁸ City of Hope, Duarte, CA, USA.
⁹ The Emmes Company, Rockville, MD, USA.
¹⁰ Wake Forest Baptist, Winston-Salem, NC, USA.
¹¹ Mount Sinai Hospital, New York, NY, USA.
¹² Memorial Sloan Kettering Cancer Center, New York, NY, USA.
¹³ University of North Carolina Medical Center, Chapel Hill, NC, USA.
¹⁴ Barnes-Jewish Hospital, Washington University, St. Louis, MO, USA.
¹⁵ Virginia Commonwealth University, Richmond, VA, USA.
¹⁶ University of Kansas, Lawrence, KS, USA.
¹⁷ Medical College of Wisconsin, Milwaukee, WI, USA.
¹⁸ National Cancer Institute, Bethesda, MD, USA.
¹⁹ National Marrow Donor Program/Center for International Blood and Marrow Transplant Research, Minneapolis, MN, USA.
²⁰ Lehigh Valley Health Network, Allentown, PA, USA.
²¹ The Leukemia and Lymphoma Society, Rye Brook, New York, NY, USA.
²² Nationwide Children's Hospital, Columbus, OH, USA.
²³ Weill Cornell Medical College, New York, NY, USA.

Abstract

Background: The optimal timing of vaccination with SARS-CoV-2 vaccines after cellular therapy is incompletely understood.

Objective: To describe humoral and cellular responses after SARS-CoV-2 vaccination initiated <4 months versus 4-12 months after cellular therapy.

Design: Multicenter prospective observational study.

Setting: 34 centers in the United States.

Participants: 466 allogeneic hematopoietic cell transplant (HCT; n=231), autologous HCT (n=170), or chimeric antigen receptor T cell (CAR-T cell) therapy (n=65) recipients enrolled between April 2021 and June 2022.

Interventions: SARS-CoV-2 vaccination as part of routine care.

Measurements: We obtained blood prior to and after vaccinations at up to five time points and tested for SARS-CoV-2 spike (anti-S) IgG in all participants and neutralizing antibodies for Wuhan D614G, Delta B.1.617.2, and Omicron B.1.1.529 strains, as well as SARS-CoV-2-specific T cell receptors (TCRs), in a subgroup.

Results: Anti-S IgG and neutralizing antibody responses increased with vaccination in HCT recipients irrespective of vaccine initiation timing but were unchanged in CAR-T cell recipients initiating vaccines within 4 months. Anti-S IgG ^≥2,500 U/mL was correlated with high neutralizing antibody titers and attained by the last time point in 70%, 69%, and 34% of allogeneic HCT, autologous HCT, and CAR-T cell recipients, respectively. SARS-CoV-2-specific T cell responses were attained in 57%, 83%, and 58%, respectively. Humoral and cellular responses did not significantly differ among participants initiating vaccinations <4 months vs 4-12 months after cellular therapy. Pre-cellular therapy SARS-CoV-2 infection or vaccination were key predictors of post-cellular therapy anti-S IgG levels.

Limitations: The majority of participants were adults and received mRNA vaccines.

Conclusions: These data support starting mRNA SARS-CoV-2 vaccination three to four months after allogeneic HCT, autologous HCT, and CAR-T cell therapy.

Funding: National Marrow Donor Program, Leukemia and Lymphoma Society, Multiple Myeloma Research Foundation, Novartis, LabCorp, American Society for Transplantation and Cellular Therapy, Adaptive Biotechnologies, and the National Institutes of Health.

Keywords: Covid-19; SARS-CoV-2; hematopoietic cell transplant; transplant; vaccine.

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Preprint

Abstract

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