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COVID-19: Implications for patients with myeloproliferative neoplasms

Oct 29, 2020
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Little is currently known about the impact of COVID-19 on patients with myeloproliferative neoplasms (MPN). Thromboembolic events are being observed with increasing frequency in patients with COVID-19, and since patients with MPN are predisposed to thrombosis (reviewed on the MPN Hub here), a better understanding of the implications for patients with MPN who become infected with the SARS-CoV-2 virus will be key to patient management. This was the focus of two presentations at the Texas Virtual MPN Workshop (TMW) 2020: First Annual Workshop and Meeting.

MPN Hub Steering Committee member, Tiziano Barbui, Papa Giovanni XXIII Hospital, Bergamo, located at the epicenter of the COVID-19 pandemic in Italy, presented data from a European LeukemiaNet (ELN) project on COVID-19 in patients with MPN (NCT04385160), the largest observational study to date of acute phase clinical and laboratory features in such patients.1 Using the same ELN study data, Valerio De Stefano compared the thrombotic events and outcomes for patients with MPN and COVID-19 to those for patients with either COVID-19 or MPN alone.2 Here, we are pleased to summarize the key points from these presentations.

Study design and treatment1

A total of 175 patients with MPN and COVID-19 were included in this retrospective, observational study involving 38 centers from Spain, Italy, Germany, France, UK, and Poland. Selected patient characteristics and interventions are shown in Table 1.

The most common MPN therapies to be administered prior to COVID-19 diagnosis were hydroxyurea and ruxolitinib. Due to its anti-inflammatory and immunomodulatory properties, ruxolitinib is currently being investigated as a therapeutic option for severe COVID-19 (reported on the MPN Hub here). In this cohort, ruxolitinib was mostly used to treat patients with myelofibrosis (MF). There was a frequent need for respiratory support in patients with MPN and COVID-19, and heparin was used in almost all patients.

Table 1. Selected patient characteristics and interventions1

*At last follow-up (median, 1.5 months before COVID-19; range, 0.8–3.0).

ET, essential thrombocythemia; ICU, intensive care unit; IQR, interquartile range; MF, myelofibrosis; MV, myelofibrosis; pre-PMF, prefibrotic primary myelofibrosis; PV, polycythemia vera.

 

ET

(n = 51)

PV

(n = 46)

MF

(n = 60)

Pre-PMF

(n = 18)

Total

(n = 175)

Median age, years (IQR)

72.0

(54.1–80.6)

70.0

(58.2–74.7)

70.9

(62.7–77.1)

78.8

(70.3–86.4)

71.0

(60.0–79.9)

Hospitalization, %

78.4

69.6

85.0

66.7

77.1

Median O2 saturation, % (IQR)

93.0

(92.0–95.0)

94.0

(88.0–97.0)

91.0

(88.0–97.0)

91.0

(85.0–93.0)

93.0

(88.0–96.0)

Comorbidities, %

Cancer

28.0

15.2

23.3

22.2

22.4

Hypertension

66.0

60.0

57.6

58.8

60.8

Diabetes mellitus

8.0

10.9

20.0

12.5

13.4

Pre-COVID-19 cytoreduction treatment*, %

Hydroxyurea

60.8

56.5

16.7

66.7

45.1

Ruxolitinib

3.9

17.1

56.7

5.6

25.7

COVID-19 intervention, %

Respiratory support

62.7

47.8

64.4

61.1

59.2

Transfer to ICU

11.8

8.9

12.1

11.1

11.0

Antithrombotic therapy (of which heparin)

64.0

(100.0)

40.9

(94.4)

57.1

(93.5)

68.8

(100.0)

96.7

(96.7)

Mortality rates

Overall, 29% of patients died, and mortality was particularly high (40%) for those with MF.1 Mortality was more likely to occur within the first 2 weeks of COVID-19 diagnosis, and no differences were observed in survival rates according to country.1

With mean worldwide mortality rates for patients with COVID-19 in March 2020 reported at 3.7%, the mortality rate for patients with MPN and COVID-19 is approximately 8-fold higher overall, and approximately 11-fold higher for MF, than for patients without MPN.2

Risk factors for mortality1

Variables were selected for analysis according to biological plausibility and clinical relevance. Independent risk factors for mortality, identified in multivariate analysis, were as follows:

  • male (hazard ratio [HR], 2.44),
  • a diagnosis of MF (HR, 2.82),
  • need for respiratory support (HR, 7.86), and
  • intensive care admission (HR, 3.19).

Of note, treatment was not evaluated as a risk factor here because a further subanalysis is planned to establish the influence of therapies, particularly ruxolitinib, on mortality risk.

Incidence of thrombosis

Thrombosis was a frequent event in patients with MPN and COVID-19, particularly in patients with essential thrombocythemia (ET; Table 2), and was observed very soon after COVID-19 diagnosis.1 Venous thrombosis occurred in 17% of patients with ET; 75% of these had a pulmonary embolism. In these patients, median time to pulmonary embolism was 4 days (IQR, 0.0–8.0). Incidence of thrombosis was not influenced by prior history of thrombotic events.

Table 2. Incidence of thrombosis in patients with MPN and COVID-19.1

MF, myelofibrosis; MV, myelofibrosis; PE, pulmonary embolism; pre-PMF, prefibrotic primary myelofibrosis; PV, polycythemia vera.

 

ET

PV

MF

Pre-PMF

Patients with thrombosis, %

18.8

4.8

5.4

6.3

Arterial

2.1

0.0

1.8

6.3

Venous

(of which PE)

16.7

(75.0)

4.8

(100.0)

3.6

(100.0)

0.0

(–)

In his review of comparative data, Valerio De Stefano reported that patients with MPN and COVID-19 were at higher risk of thrombosis than patients with MPN but without COVID-19 infection.2 Interestingly, venous thrombosis accounted for 75% of cases in patients with MPN and COVID-19, whereas arterial thrombosis generally accounts for around two-thirds of cases for patients with MPN but without COVID-19. It was noted, however, that for patients hospitalized for acute illness, in the absence of anti-thrombotic prophylaxis, the rate of venous thrombosis is around 5%, which is comparable to that observed in patients with PV and MF.

Whether patients with MPN and COVID-19 are at a higher risk of thrombosis and major bleeding than patients with COVID-19 but without MPN is unclear since there is heterogeneity between the comparison cohorts.2 Incidence of thrombotic events in hospitalized patients with COVID-19 ranged from 2–8% overall and increased to between 20%–35% in patients admitted to intensive care. At around 10%, the incidence of thrombosis in patients with MPN and COVID-19 is similar to that for the overall population of hospitalized patients with COVID-19, but lower compared with patients in intensive care. At around 5%, the incidence of major bleeding for patients with MPN appears to be similar to the rate in other patients with COVID-19. However, due to conflicting data from the literature, a thorough assessment of the bleeding risk remains currently inconclusive.

Conclusions

Patients with MPN and COVID-19 have a higher risk of thrombosis than patients with MPN alone, likely due to the increased risk associated with hospitalization for acute illness. Incidence of venous thromboembolism was higher in patients with ET than patients with PV or MF, which may be attributed to a more severe SARS-CoV-2 infection. In general, the incidence of thrombosis is no greater for patients with MPN and COVID-19 than for the overall COVID-19 patient population, however mortality risk is greater for all patients with MPN, particularly those with MF. Further analysis is in progress to explore the influence of low molecular weight heparin on patient outcomes, and an extended study is planned until the end of this year to evaluate the long-term sequelae of COVID-19 infection in patients with MPN.

  1. Barbui, T. European LeukemiaNet project on COVID in patients with myeloproliferative neoplasms. Texas MPN Workshop (TMW) 2020: First Annual Workshop and Meeting; Aug 28, 2020; Virtual.
  2. De Stefano, V. Thrombosis issues in MPN-COVID. Texas MPN Workshop (TMW) 2020: First Annual Workshop and Meeting; Aug 28, 2020; Virtual.

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