Humoral and cellular immune responses after three or four doses of BNT162b2 in patients with hematological malignancies

Line Dam Heftdal, Sebastian Rask Hamm, Laura Pérez-Alós, Johannes Roth Madsen, Jose Juan Almagro Armenteros, Kamille Fogh, Christoffer Cronwald Kronborg, Anders Pommer Vallentin, Rasmus Bo Hasselbalch, Dina Leth Møller, Cecilie Bo Hansen, Mia Pries-Heje, Anne Ortved Gang, Sisse Rye Ostrowski, Ruth Frikke-Schmidt, Erik Sørensen, Linda Hilsted, Henning Bundgaard, Kasper Iversen, Peter GarredSusanne Dam Nielsen, Kirsten Grønbaek*

*Corresponding author for this work
2 Citations (Scopus)


OBJECTIVES: Initial responses to coronavirus disease 2019 vaccination are impaired in patients with hematological malignancies. We investigated immune responses after three or four doses of BNT162b2 in patients with myeloid and lymphoid malignancies compared to controls, and identified risk factors for humoral and cellular nonresponse 1 year after first vaccination.

METHODS: In 407 hematological patients (45 myeloid, 362 lymphoid) and 98 matched controls, we measured immunoglobulin G (IgG) and neutralizing antibodies specific for the receptor-binding domain of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) at baseline, 3 weeks, 2, 6, and 12 months, and interferon-γ release at 12 months.

RESULTS: In patients with lymphoid malignancies, SARS-CoV-2 receptor-binding domain IgG concentration and mean neutralizing capacity was lower than in controls at all time points. A diagnosis of chronic lymphocytic B-cell leukemia (CLL) or lymphoma was associated with humoral nonresponse at 12 months compared to having multiple myeloma/amyloidosis (p < .001 and p = .013). Compared to controls, patients with lymphoid malignancies had increased risk of cellular nonresponse. A lymphoma diagnosis was associated with lower risk of cellular nonresponse compared to patients with multiple myeloma/amyloidosis, while patients with CLL had comparable response rates to patients with multiple myeloma/amyloidosis (p = .037 and p = .280).

CONCLUSIONS: In conclusion, long-term humoral and cellular immune responses to BNT162b2 were impaired in patients with lymphoid malignancies.

Original languageEnglish
JournalEuropean Journal of Haematology
Issue number2
Pages (from-to)229-239
Number of pages11
Publication statusPublished - Aug 2023


  • Amyloidosis
  • Antibodies, Viral
  • BNT162 Vaccine
  • COVID-19
  • Hematologic Neoplasms/diagnosis
  • Humans
  • Immunity, Cellular
  • Immunoglobulin G
  • Leukemia, Lymphocytic, Chronic, B-Cell
  • Multiple Myeloma
  • SARS-CoV-2
  • Vaccination


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