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

Haggenburg, S.; Lissenberg-Witte, B.I.; Binnendijk, R.S. van; Hartog, G. den; Bhoekhan, M.S.; Haverkate, N.J.E.; Rooij, D.M. de; Meerloo, J. van; Cloos, J.; Kootstra, N.A.; Wouters, D.; Weijers, S.S.; Leeuwen, E.M.M. van; Bontkes, H.J.; Tonouh-Aajoud, S.; Heemskerk, M.H.M.; Sanders, R.W.; Roelandse-Koop, E.; Hofsink, Q.; Groen, K.; Cetinel, L.; Schellekens, L.; Hartog, Y.M. den; Toussaint, B.; Kant, I.M.J.; Graas, T.; Pater, E. de; Dik, W.A.; Engel, M.D.; Pierie, C.R.N.; Janssen, S.R.; Dijkman, E. van; Poniman, M.; Burger, J.A.; Bouhuijs, J.H.; Smits, G.; Rots, N.Y.; Zweegman, S.; Kater, A.P.; Meerten, T. van; Mutsaers, P.G.N.J.; Doesum, J.A. van; Broers, A.E.C.; Gils, M.J. van; Goorhuis, A.; Rutten, C.E.; Hazenberg, M.D.; Nijhof, I.S.

doi:doi:10.1182/bloodadvances.2021006917

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-dosemRNA-1273 (Spikevax/Moderna) vaccination in hematology patients. Obtaining S1 IgG >= 300 binding antibody units (BAUs)/mLwas 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-dosemRNA-1273. All patients with sickle cell disease or chronicmyeloid leukemia obtained adequate antibody concentrations. Around 70% of patients with chronic graft-versus-host disease (cGVHD),...Show moreVaccination 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-dosemRNA-1273 (Spikevax/Moderna) vaccination in hematology patients. Obtaining S1 IgG >= 300 binding antibody units (BAUs)/mLwas 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-dosemRNA-1273. All patients with sickle cell disease or chronicmyeloid 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 inmyeloidmalignancies. 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 <= 2months formultiplemyeloma, 8months 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 fromvaccination.Show less

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