Quantitative analysis of mRNA-1273 COVID-19 vaccination response in immunocompromised adult hematology patients.

Abstract

Vaccination guidelines for patients treated for hematological diseases are typically conservative. Given their high risk for severe COVID-19, it is important to identify those patients that benefit from vaccination. We prospectively quantified serum immunoglobulin G (IgG) antibodies to spike subunit 1 (S1) antigens during and after 2-dose mRNA-1273 (Spikevax/Moderna) vaccination in hematology patients. Obtaining S1 IgG ≥ 300 binding antibody units (BAUs)/mL was considered adequate as it represents the lower level of S1 IgG concentration obtained in healthy individuals, and it correlates with potent virus neutralization. Selected patients (n = 723) were severely immunocompromised owing to their disease or treatment thereof. Nevertheless, >50% of patients obtained S1 IgG ≥ 300 BAUs/mL after 2-dose mRNA-1273. All patients with sickle cell disease or chronic myeloid leukemia obtained adequate antibody concentrations. Around 70% of patients with chronic graft-versus-host disease (cGVHD), multiple myeloma, or untreated chronic lymphocytic leukemia (CLL) obtained S1 IgG ≥ 300 BAUs/mL. Ruxolitinib or hypomethylating therapy but not high-dose chemotherapy blunted responses in myeloid malignancies. Responses in patients with lymphoma, patients with CLL on ibrutinib, and chimeric antigen receptor T-cell recipients were low. The minimal time interval after autologous hematopoietic cell transplantation (HCT) to reach adequate concentrations was <2 months for multiple myeloma, 8 months for lymphoma, and 4 to 6 months after allogeneic HCT. Serum IgG4, absolute B- and natural killer-cell number, and number of immunosuppressants predicted S1 IgG ≥ 300 BAUs/mL. Hematology patients on chemotherapy, shortly after HCT, or with cGVHD should not be precluded from vaccination. This trial was registered at Netherlands Trial Register as #NL9553.

• Authors: Sabine Haggenburg, Birgit I Lissenberg-Witte, Rob S van Binnendijk, Gerco den Hartog, Michel S Bhoekhan, Nienke J E Haverkate, Dennis M de Rooij, Johan van Meerloo, Jacqueline Cloos, Neeltje A Kootstra, Dorine Wouters, Suzanne S Weijers, Ester M M van Leeuwen, Hetty J Bontkes, Saïda Tonouh-Aajoud, Mirjam H M Heemskerk, Rogier W Sanders, Elianne Roelandse-Koop, Quincy Hofsink, Kazimierz Groen, Lucia Çetinel, Louis Schellekens, Yvonne M den Hartog, Belle Toussaint, Iris M J Kant, Thecla Graas, Emma de Pater, Willem A Dik, Marije D Engel, Cheyenne R N Pierie, Suzanne R Janssen, Edith van Dijkman, Meliawati Poniman, Judith A Burger, Joey H Bouhuijs, Gaby Smits, Nynke Y Rots, Sonja Zweegman, Arnon P Kater, Tom van Meerten, Pim G N J Mutsaers, Jaap A van Doesum, Annoek E C Broers, Marit J van Gils, Abraham Goorhuis, Caroline E Rutten, Mette D Hazenberg, Inger S Nijhof
• Journal: Blood advances (Blood Adv) Vol. 6 Issue 5 Pg. 1537-1546 (03 08 2022) ISSN: 2473-9537 [Electronic] United States
• PMID: 35114690 (Publication Type: Clinical Trial, Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: © 2022 by The American Society of Hematology. Licensed under Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International (CC BY-NC-ND 4.0), permitting only noncommercial, nonderivative use with attribution. All other rights reserved.

Chemical References

• COVID-19 Vaccines
• 2019-nCoV Vaccine mRNA-1273

Topics

• 2019-nCoV Vaccine mRNA-1273
• COVID-19 (prevention & control)
• COVID-19 Vaccines
• Hematology
• Humans
• SARS-CoV-2
• Vaccination