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Chronic lymphocytic leukemia (CLL) is the most common type of leukemia in Western countries, predominantly affecting older patients and characterized by several alterations in the way the immune system functions. The advent of the SARS-CoV-2 pandemic has been challenging for patients with CLL, who are predisposed to infections due to the immunodeficiency related to the leukemia itself and to immunosuppression caused by cumulative treatments. The novel coronavirus activates a severe, aberrant, and uncontrollable inflammatory response, known as a cytokine storm, involving both innate and adaptive responses and leading to major acute clinical complications and high mortality rates for this high-risk group.
Ibrutinib is a Bruton’s tyrosine kinase (BTK) inhibitor with clinical efficacy for patients with relapsed/refractory CLL. Recent studies have suggested that ibrutinib could also offer protection against lung injury in patients with CLL and COVID-19 by moderating the hyperinflammatory state and managing better outcomes and shorter hospitalization. Despite this, BTK inhibitor treatment is often interrupted at the onset of COVID-19.
In a letter to the editor recently published in Haematologica, Stefania Fiorcari and colleagues examined the modulation of treatment with ibrutinib on the cytokines released by monocytes (CD14+) and T cells (CD3+) in patients with CLL and an active COVID-19 infection.1
Following stimulation of PBMCs from treatment-naïve patients with SARS-CoV-2 peptides, the investigators observed:
The following immunomodulatory modifications were reported following treatment with ibrutinib in the presence of stimulation with SARS-CoV-2 peptides:
CLL patient samples before treatment and after 3 months of treatment with ibrutinib were evaluated to compare the response of CD3+ and CD14+ cells to SARS-CoV-2:
According to the available evidence, the inhibition of BTK, expressed by myeloid immune cells, does not seem to worsen the COVID-19-specific immune response, but rather it appears to mitigate inflammation through the NF-κB pathway and improve resolution of infection. The results of this study indicate a protective action of ibrutinib against COVID-19 by limiting the inflammatory cytokine storm and preventing lung injury, hence providing a rationale for continuation of ibrutinib treatment in patients with CLL who develop a SARS-CoV-2 infection.
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Treatment with ublituximab plus ibrutinib versus ibrutinib alone: A phase III randomised trial (GENUINE) for patients with relapsed or refractory high-risk CLL
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