ABSTRACT
SARS-CoV-2 infection, and resulting disease, COVID-19, has a high mortality amongst patients with haematological malignancies. Global vaccine rollouts have reduced hospitalisations and deaths, but vaccine efficacy in patients with haematological malignancies is known to be reduced. The UK-strategy offered a third, mRNA-based, vaccine as an extension to the primary course in these patients. The MARCH database is a retrospective observational study of serological responses in patients with blood disorders. Here we present data on 381 patients with haematological malignancies. By comparison with healthy controls, we report suboptimal responses following two primary vaccines, with significantly enhanced responses following the third primary dose. These responses however are heterogeneous and determined by haematological malignancy sub-type and therapy. We identify a group of patients with continued suboptimal vaccine responses who may benefit from additional doses, prophylactic extended half-life neutralising monoclonal therapies (nMAB) or prompt nMAB treatment in the event of SARS-CoV-2 infection.
Subject(s)
COVID-19 , Hematologic Neoplasms , Viral Vaccines , Humans , COVID-19 Vaccines , SARS-CoV-2 , COVID-19/prevention & control , Antibody Formation , Hematologic Neoplasms/therapy , Antibodies, ViralABSTRACT
SARS-CoV-2 infection, and resulting disease, COVID-19, has a high mortality amongst patients with haematological malignancies. Global vaccine rollouts have successfully reduced hospitalisations and deaths, but the efficacy of vaccination in patients with haematological malignancies is known to be reduced. The UK-strategy offered a third, mRNA-based, vaccine as an extension to the primary course in these patients. Here we quantify serological responses following these vaccines in a cohort of 381 patients with haematological malignancies attending routine haematology outpatient clinics. By comparison with healthy controls, we report suboptimal responses following two primary vaccines, with significantly enhanced responses following the third primary dose. These responses however are heterogeneous and determined by haematological malignancy sub-type and therapy. We identify a group of patients with continued sub-optimal vaccine responses who may benefit from additional doses, as well as early intervention with monoclonal therapies in the event of developing SARS-CoV-2 infection.
Subject(s)
COVID-19 , Leukemia, Myelogenous, Chronic, BCR-ABL Positive , Antibodies, Viral , COVID-19/prevention & control , COVID-19 Vaccines , Humans , Leukemia, Myelogenous, Chronic, BCR-ABL Positive/drug therapy , Protein Kinase Inhibitors/pharmacology , Protein Kinase Inhibitors/therapeutic useABSTRACT
Immune modulation in COVID-19 is emerging as an important therapeutic strategy as increasing evidence suggests that inflammatory pathways are implicated in lung damage. Bruton tyrosine kinase inhibitors (BTKi), such as ibrutinib, are commonly used to treat indolent B-cell neoplasms and chronic graft-versus-host disease (GvHD). Given their potential to suppress pulmonary inflammatory cytokines and lessen acute lung injury, this could be applicable in the context of hospitalised COVID-19 patients. We describe an 81 year-old male receiving ibrutinib for Waldenstrom macroglobulinaemia (WM) who was hospitalised with COVID-19. On stopping the BTKi due to concerns of additional immunosuppression, he required non-invasive ventilation (NIV) in the intensive care unit (ICU) and demonstrated prompt clinical recovery when ibrutinib was reinstated. Continuing ibrutinib in patients with COVID-19 may be advantageous given its immunomodulatory properties and withdrawal of ibrutinib therapy may be detrimental. Further evidence is required to explore the potential therapeutic impact of BTKis and other immunomodulatory agents on the clinical course of COVID-19 as is currently being carried out in a number of clinical trials.