Impaired response to first SARS-CoV-2 dose vaccination in myeloproliferative neoplasm patients receiving ruxolitinib

American Journal of Hematology

 

Published July 31, 2021

COVID19, the disease caused by pandemic SARSCoV2 infection, had significant impact on patients with hematologic conditions; a metaanalysis involving 3,377 patients with hematologic malignancies who were affected by COVID19 reported a mortality rate of 34%. A similarly dismal outcome was documented among 175 patients with chronic myeloproliferative neoplasms (MPN), collected in a European observational study, where mortality rate was 30% for the entire cohort, reaching 48% in primary overt myelofibrosis (MF). COVID19 was also associated with higher incidence of thrombosis in patients with essential thrombocythemia (ET), compared to MF and polycythemia vera (PV) (20% versus 5% for both, respectively). Finally, MPN patients surviving the acute phase may suffer from additional longterm sequelae from COVID-19, that furtherly increase mortality and morbidity.
The JAK1 and JAK2 inhibitor (JAKi) ruxolitinib is approved for the treatment of patients with MF and hydroxyurea resistant/refractory PV. By inhibiting JAKSTAT signaling, ruxolitinib has profound effects on different cell compartments of the immune system, including T cells, natural killer, and dendritic cells, in addition to potently dampening inflammatory cytokine production. These properties have been mechanistically linked to the increased rate of infections in MPN patients receiving ruxolitinib, and, conversely, were explored successfully in the setting of steroid-refractory acute graft versus host disease following allogeneic stem cell transplantation. In the above cited European study in MPN, rapid discontinuation of the drug was implicated in 75% of deaths occurring in the ruxolitinibtreated cohort; these were ascribed to a previously described discontinuation syndrome”, a potentially fatal complication due to a cytokine storm that follows the abrupt suspension of ruxolitinib. In fact, observational studies support the effectiveness of ruxolitinib to quench the hyperflammatory reaction accompanying COVID19 in the general population. Due to the immunomodulatory properties of ruxolitinib, the question arises
whether response to vaccination for SARSCoV2 in patients under stable ruxolitinib therapy might be impaired.
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