MPN patients show higher mortality with COVID-19 ‘ruxolitinib discontinuation syndrome’

Patients with myeloproliferative neoplasms (MPN) face a higher mortality risk from COVID-19 infections than the general population, according to a new study.

The findings, published in Nature, also show that patients who discontinued ruxolitinib therapy had a ‘striking’ increase in risk of death compared to patients who continued taking the drug.

Prior to this, there was limited information on outcomes of patients with MPN and COVID-19, the researchers said.

“Natural history of MPN is marked by a high incidence of thrombosis and haemorrhagic complications and by a natural propensity to transform into overt MF and acute leukaemia,” wrote study authors, led by Professor Tiziano Barbui, Haematologist at the Bergamo Hospital, Italy.

The study was conducted across six European countries, and included a total of 175 patients with essential thrombocythemia (51 patients), polycythemia vera (46 patients), myelofibrosis (60 patients), or prefibrotic primary myelofibrosis (18 patients).

Following COVID-19 diagnosis, 77% of the patients in the cohort were hospitalised. A total of 59.2% required respiratory support, about half of whom were managed with noninvasive support.

A total of 50 patients (28.6%) in the cohort died after a median of 9.5 days following diagnosis. Myelofibrosis appeared to have the highest mortality risk; compared with the other MPNs, myelofibrosis patients had a significantly reduced survival probability (P = 0.023).

There was no difference in survival with regard to driver mutations, palpable splenomegaly, duration of MPN disease, or blood counts; the only exception to the latter was a decreased lymphocyte count and higher neutrophil/lymphocyte ratio seen in those who died.

At the time of COVID-19 diagnosis, approximately one-quarter of the cohort were receiving ruxolitinib (25.7%), while 45.1% were receiving hydroxyurea. A total of 11.4% and 24.4% of those on hydroxyurea and ruxolitinib, respectively, stopped treatment after COVID-19 diagnosis.

The probability of survival 60 days after COVID-19 diagnosis was 68% in patients who continued ruxolitinib therapy, compared with only 11% in those who discontinued the drug (P < 0.001). No such difference was seen in patients who stopped taking hydroxyurea.

“The biological plausibility of this effect may be related to the devastating enhancement of inflammation (‘cytokine storm’) that follows the abrupt suspension of ruxolitinib, leading to the ‘ruxolitinib discontinuation syndrome’, which in turn may lead to fatal clinical complications and multiorgan failure,” the study authors wrote.

They noted the study was limited by a relatively small number of patients, especially in the group that discontinued ruxolitinib. Still, a number of adjustments and sensitivity analyses were conducted to confirm the results.

“We believe this work suggests that ruxolitinib treatment in MPN patients who are already [receiving] it at COVID-19 diagnosis should be continued, in agreement with the ASH recommendations,” they concluded.

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