Haggenburg S, Lissenberg-Witte BI, van Binnendijk RS, den Hartog G, Bhoekhan MS, Haverkate NJE, de Rooij DM, van Meerloo J, Cloos J, Kootstra NA, Wouters D, Weijers SS, van Leeuwen EMM, Bontkes HJ, Tonouh-Aajoud S, Heemskerk MHM, Sanders RW, Roelandse-Koop E, Hofsink Q, Groen K, Çetinel L, Schellekens L, den Hartog YM, Toussaint B, Kant IMJ, Graas T, de Pater E, Dik WA, Engel MD, Pierie CRN, Janssen SR, van Dijkman E, Poniman M, Burger JA, Bouhuijs JH, Smits G, Rots NY, Zweegman S, Kater AP, van Meerten T, Mutsaers PGNJ, van Doesum JA, Broers AEC, van Gils MJ, Goorhuis A, Rutten CE, Hazenberg MD, and Nijhof IS
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., (© 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.)