How Do Patients With Myeloproliferative Neoplasms Fare After COVID-19 Infection?

Two analyses from the MPN-COVID study from a group of researchers led by Tiziano Barbui, MD, of the United Hospitals of Bergamo in Italy, describe the outcomes for patients with myeloproliferative neoplasms (MPNs) who have been diagnosed with COVID-19.1,2 Overall, patients with essential thrombocythemia (ET) have an increased risk of venous thromboembolism (VTE) and patients with MPNs had higher rates of mortality compared with the general population – particularly those with myelofibrosis (MF) or who discontinued ruxolitinib at the time of COVID-19 diagnosis.

The MPN-COVID study is a retrospective, multicenter cohort study that included 180 patients from 38 hematology units in Europe. Eligible patients had MPNs (including ET, MF, and polycythemia vera [PV]) and a diagnosis of COVID-19 between February and May 2020.

In the first analysis, published in Blood Cancer Journal, Dr. Barbui and researchers examined VTE risk among 162 study participants who had a minimum follow-up of one month.

Diagnoses in this group included ET (n=48), PV (n=42), MF (n=56), and prefibrotic myelofibrosis (n=16). Fourteen patients experienced a total of 15 major thromboses, including three arterial and 12 venous events. All but one of these patients were receiving low-molecular-weight heparin prophylaxis.

Over a median follow-up period of 50.5 days, a total of 19 patients experienced thrombo-hemorrhagic events at home (2.5%), during hospitalization in regular wards (12.4%), or in the intensive care unit (ICU; 29.4%) during the acute phase of infection (p=0.016). After 60 days of follow-up, the cumulative incidence of thrombosis, adjusted for the competing risk of death, reached 8.5%.

Most thrombotic events were VTE (7.4%), which were detected at a higher frequency in patients with ET versus PV or MF (16.7% vs. 4.8% vs. 3.6%, respectively; p=0.031). Notably, eight of the 12 VTEs observed occurred in patients with ET.

At the time of COVID-19 diagnosis, individuals had significantly lower platelet counts compared with their last pre-COVID follow-up, which was conducted at a median of 47 days prior to the COVID-19 diagnosis (median = 250.5×109/L vs. 326×109/L; p<0.0001). According to the investigators, this decline in platelet count was much higher in patients with ET (−23.3%; p<0.0001), compared to those with PV (−16.4%; p=0.1730). This decline also correlated with a significantly higher mortality rate for pneumonia (p=0.001). Pneumonia was reported in a greater proportion of patients with ET versus PV and MF.

Other independent risk factors for thrombosis included transfer to the intensive care unit (ICU; sub-distribution hazard ratio [SHR] = 3.73; p=0.029), neutrophil/lymphocyte ratio (SHR=1.1; p=0.001), and ET phenotype (SHR=4.37; p=0.006).

These results suggest that the increased susceptibility to ET-associated VTE in patients with COVID-19 and MPNs “may recognize a common biological plausibility and deserve to be delved to tailor new antithrombotic regimens including antiplatelet drugs.”

In the second analysis, published in Leukemia, Dr. Barbui and colleagues evaluated data from 175 patients with MPNs and COVID-19, finding that these patients had a higher risk for mortality than the general population diagnosed with COVID-19, and factors such as abrupt withdrawal of ruxolitinib further increased this risk.

Patients were followed for a median of 50 days and a total of 50 of patients died (28.6%). The median time from diagnosis to death was 9.5 days.

The only MPN phenotype that correlated significantly with survival was MF, which had a mortality rate of 48% compared with 28.8% in other MPNs (p=0.016). Other factors associated with higher mortality rates included treatment in the ICU, compared with patients treated in the regular ward and at home (50% vs. 25% and 6%, respectively; p<0.001).

Regarding MPN-directed treatment, the most common treatments at the time of COVID-19 diagnosis were hydroxyurea (45.1%) and ruxolitinib (25.7%). Nearly 20% of patients were not taking any MPN-directed therapy. After diagnosis of COVID-19, 11.4% of patients receiving hydroxyurea and 24.4% of patients receiving ruxolitinib discontinued their respective treatments. The authors reported that a significantly greater proportion of patients who died during follow-up were treated with ruxolitinib compared with survivors (40% vs. 20%, respectively; p=0.006).

In a logistic multivariable model, ruxolitinib discontinuation was one of the factors associated with the highest risk for mortality (odds ratio [OR] = 8.4; p=0.04). Only the need for respiratory support was considered a stronger risk factor (OR=10.4; p<0.001). The researchers explained, however, that the confidence intervals for ruxolitinib discontinuation were wide, possibly because of the low number of events compared with the number of confounders.

Despite study limitations such as a relatively small sample size and small number of events, the authors argue that the results from this analysis suggest clinicians should continue treatment with ruxolitinib in patients with MPNs who are already receiving it at the time of a COVID-19 diagnosis, per American Society of Hematology recommendations.

Study authors report no relevant conflicts of interest.

References

  1. Barbui T, De Stefano V, Alvarez-Larran A, et al. Among classic myeloproliferative neoplasms, essential thrombocythemia is associated with the greatest risk of venous thromboembolism during COVID-19. Blood Cancer J. 2021;11(2):21.
  2. 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. 2021;35(2):485-493.