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

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 GroenLucia 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

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review


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 5 723) 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.

Original languageEnglish
Pages (from-to)1537-1546
Number of pages10
Issue number5
Publication statusPublished - 8 Mar 2022

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