by Dr. Srdan Verstovsek MD, PhD. The United Energy Resources, Inc., Professor of Medicine and hematologist-oncologist at MD Anderson. Dr. Verstovsek is a global leader in myeloproliferative neoplasms (MPN) and the Founder/Director of the largest MPN Clinical Research Center worldwide
The respiratory illness syndrome named coronavirus disease 2019 (COVID-19) is a contagious disease caused by the newly diagnosed coronavirus severe acute respiratory syndrome-coronavirus 2 (SARS-CoV-2). The COVID-19 pandemic has challenged the health care system and severely impacted many aspects of our society on a global level. COVID-19 manifests a wide clinical spectrum ranging from asymptomatic infection, mild upper respiratory tract illness; and severe pneumonia with respiratory failure and high risk of death. Major complications are more likely to occur in older patients and those with pre-existing conditions. In addition, patients infected with COVID-19 have a higher risk of thrombosis (blood clotting). Clinical experience has shown that critically ill patients present a severe over-reaction of the immune system named “cytokine storm”, which is attributed to an overproduction of several pro-inflammatory cytokines (small proteins in the blood that are important for cell function). Patients with severe COVID-19 infection are treated with medications that decrease inflammation in the body, for example, corticosteroids and JAK inhibitors.
The three chronic myeloproliferative neoplasms (MPNs) are myelofibrosis (MF), polycythemia vera (PV), and essential thrombocythemia (ET). MPNs can decrease survival, especially in the case of MF, the most aggressive MPN (the expected survival is about 5-7 years). Furthermore, MPNs are associated with a higher risk of thrombosis and hemorrhagic complications than the general population. Ruxolitinib is a JAK1/2 inhibitor (inhibits proteins in the body called JAK1 and JAK2) that has emerged as the standard of care medication for MF and a second-line agent for PV. It is good anti-proliferative and anti-inflammatory medication. Other JAK1/2 inhibitors can be prescribed for different types of inflammatory and autoimmune diseases (where the immune system attacks the cells in the body). During the past year, JAK1/2 inhibitors have been evaluated as a treatment for patients with severe COVID-19 infection because of its established broad and fast anti-inflammatory effects.
Until the present, however, there were no reports about the outcome of patients who were on ruxolitinib as a therapy for their MPN, that became infected with COVID-19 and ruxolitinib was stopped at that time. The topic of interest is whether stopping ruxolitinib, an anti-inflammatory agent, at the time of acquiring COVID-19 infection impacts the outcome of the MPN patients.
To address this important matter, Dr. Barbui and colleagues recently reported the clinical features and risk factors that affected the survival of 175 patients with MPN and a concurrent COVID-19 infection. The patients were diagnosed with MPN between February and June 2020 at 38 medical centers and were monitored for an average follow-up period of 50 days. The estimated mortality of MPN patients during COVID-19 infection was higher as compared to the general population, and mortality was highest in MF patients. A noteworthy observation emerging from this study was the significant increase in the risk of death related to discontinuation of ruxolitinib treatment after COVID-19 diagnosis versus ongoing ruxolitinib treatment. Statistical analysis of the data showed that the subgroup continuing ruxolitinib had 68% probability to survive as compared to only 11% in the subgroup that discontinued the medication. The benefit that ruxolitinib treatment confers to MPN patients may be attributed to the drug’s anti-inflammatory effect on the “cytokine storm” (severe over-reaction of the immune system) that is triggered in advanced stages of COVID-19 infection. Sudden discontinuation of ruxolitinib likely underlies the devastating enhancement of inflammation and the ensuing fatal clinical implications in MPN patients infected with COVID-19. These findings merit further investigation of the critical role that ruxolitinib treatment plays in decreasing the mortality of MPN patients who acquire COVID-19 infection.
Two Year TKI Consolidation Allowed for TKI Cessation in Select Patients With CML
Research suggests some patients with CML can safely discontinue TKI therapy - NCCN guidelines published.
The American Society of Hematology (ASH) has appointed MPN experts across the globe to provide advice regarding management of MPN patients who get infected with COVID-19. On the basis of the experience acquired during the past year, the general recommendation for MPN patients is to adhere to the treatment and management they followed prior to COVID-19 onset. These recommendations are in agreement with the results of the present study.
- Barbui T, Vannucchi AM, Alvarez-Larran A, et al. High-mortality rate in COVID-19 patients with myeloproliferative neoplasms after abrupt withdrawal of ruxolitinib. Leukemia. 2020;35(2):485-493.
- Satarker S, Tom AA, Shaji RA, Alosious A, Luvis M, Nampoothiri M. JAK-STAT pathway inhibition and their implications in COVID-19 therapy. Postgrad. Medicine. 2020 Dec 16;1-19.
- Botta C, Indrieri A, Garofalo E, et al. COVID-19: High-JAKing of the inflammatory “flight” by Ruxolitinib to avoid the cytokine storm. Frontiers Oncol. 2021;10:599502.