High mortality rate in COVID-19 patients with myeloproliferative neoplasms after abrupt withdrawal of ruxolitinib.
Aged
COVID-19
/ complications
Europe
/ epidemiology
Female
Follow-Up Studies
Humans
Male
Middle Aged
Myeloproliferative Disorders
/ drug therapy
Nitriles
Prognosis
Pyrazoles
/ administration & dosage
Pyrimidines
Retrospective Studies
SARS-CoV-2
/ isolation & purification
Survival Rate
Withholding Treatment
/ statistics & numerical data
Journal
Leukemia
ISSN: 1476-5551
Titre abrégé: Leukemia
Pays: England
ID NLM: 8704895
Informations de publication
Date de publication:
02 2021
02 2021
Historique:
received:
07
10
2020
accepted:
27
11
2020
revised:
29
10
2020
pubmed:
9
1
2021
medline:
16
2
2021
entrez:
8
1
2021
Statut:
ppublish
Résumé
We report the clinical presentation and risk factors for survival in 175 patients with myeloproliferative neoplasms (MPN) and COVID-19, diagnosed between February and June 2020. After a median follow-up of 50 days, mortality was higher than in the general population and reached 48% in myelofibrosis (MF). Univariate analysis, showed a significant relationship between death and age, male gender, decreased lymphocyte counts, need for respiratory support, comorbidities and diagnosis of MF, while no association with essential thrombocythemia (ET), polycythemia vera (PV), and prefibrotic-PMF (pre-PMF) was found. Regarding MPN-directed therapy ongoing at the time of COVID-19 diagnosis, Ruxolitinib (Ruxo) was significantly more frequent in patients who died in comparison with survivors (p = 0.006). Conversely, multivariable analysis found no effect of Ruxo alone on mortality, but highlighted an increased risk of death in the 11 out of 45 patients who discontinued treatment. These findings were also confirmed in a propensity score matching analysis. In conclusion, we found a high risk of mortality during COVID-19 infection among MPN patients, especially in MF patients and/or discontinuing Ruxo at COVID-19 diagnosis. These findings call for deeper investigation on the role of Ruxo treatment and its interruption, in affecting mortality in MPN patients with COVID-19.
Identifiants
pubmed: 33414483
doi: 10.1038/s41375-020-01107-y
pii: 10.1038/s41375-020-01107-y
pmc: PMC7789078
doi:
Substances chimiques
Nitriles
0
Pyrazoles
0
Pyrimidines
0
ruxolitinib
82S8X8XX8H
Types de publication
Journal Article
Multicenter Study
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
485-493Commentaires et corrections
Type : CommentIn
Type : CommentIn
Références
Richardson S, Hirsch JS, Narasimhan M, Crawford JM, McGinn T, Davidson KW, et al. Presenting characteristics, comorbidities, and outcomes among 5700 patients hospitalized with COVID-19 in the New York City Area. JAMA. 2020;323:2052–9.
doi: 10.1001/jama.2020.6775
Xu J, Wang L, Zhao L, Li F, Liu J, Zhang L, et al. Risk assessment of venous thromboembolism and bleeding in COVID-19 patients. Research Square 2020. On line publication. https://doi.org/10.21203/rs.3.rs-18340/v1 .
Carsana L, Sonzogni A, Nasr A, Rossi RS, Pellegrinelli A, Zerbi P, et al. Pulmonary post-mortem findings in a series of COVID-19 cases from northern Italy: a two-centre descriptive study. Lancet Infect Dis. 2020;20:1135–40.
doi: 10.1016/S1473-3099(20)30434-5
Breccia M, Piciocchi A, De Stefano V, Finazzi G, Iurlo A, Fazi P, et al. COVID-19 in Philadelphia-negative myeloproliferative disorders: a GIMEMA survey. Leukemia. 2020;34:2813–4.
doi: 10.1038/s41375-020-01032-0
Palandri F, Piciocchi A, De Stefano V, Breccia M, Finazzi G, Iurlo A, et al. How the coronavirus pandemic has affected the clinical management of Philadelphia-negative chronic myeloproliferative neoplasms in Italy-a GIMEMA MPN WP survey. Leukemia. 2020;34:2805–8.
doi: 10.1038/s41375-020-0953-3
Barbui T, Tefferi A, Vannucchi AM, Passamonti F, Silver RT, Hoffman R, et al. Philadelphia chromosome-negative classical myeloproliferative neoplasms: revised management recommendations from European LeukemiaNet. Leukemia. 2018;32:1057–69.
doi: 10.1038/s41375-018-0077-1
Rosenbaum PR, Rubin DB. The central role of the propensity score in observational studies for causal effects. Biometrika. 1983;70:41–55.
doi: 10.1093/biomet/70.1.41
Vannucchi AM, Sordi B, Morettini A, Nozzoli C, Poggesi L, Pieralli F, et al. Compassionate use of JAK1/2 inhibitor ruxolitinib for severe COVID-19: a prospective observational study. Leukemia. 2020;19:1–13.
Pemmaraju N, Yu J, Parasuraman S, Paranagama D, Kish J, Visaria J, et al. Ruxolitinib (RUX) retreatment in patients (Pts) with myelofibrosis (MF): Real-world evidence on pt characteristics and outcomes. J Clin Onc. 2020;38:e19535.
Passamonti F, Cattaneo C, Arcaini L, Bruna R, Cavo M, Merli F, et al. Clinical characteristics and risk factors associated with COVID-19 severity in patients with haematological malignancies in Italy: a retrospective, multicentre, cohort study. Lancet Haematol. 2020;7:e737–45.
doi: 10.1016/S2352-3026(20)30251-9
Onder G, Rezza G, Brusaferro S. Case-fatality rate and characteristics of patients dying in relation to COVID-19 in Italy. JAMA. 2020;323:1775–6.
pubmed: 32203977
Posso M, Comas M, Román M, Domingo L, Louro J, González C, et al. Comorbidities and mortality in patients with COVID-19 aged 60 years and older in a university hospital in Spain. Arch Bronconeumol. 2020;S0300-2896:30215–5.
Tefferi A, Pardanani A. Serious adverse events during ruxolitinib treatment discontinuation in patients with myelofibrosis. Mayo Clin Proc. 2011;86:1188–91.
doi: 10.4065/mcp.2011.0518
Coltro G, Mannelli F, Guglielmelli P, Pacilli A, Bosi A, Vannucchi AM. A life-threatening ruxolitinib discontinuation syndrome. Am J Hematol. 2017;92:833–8.
doi: 10.1002/ajh.24775
La Rosée F, Bremer HC, Gehrke I, Kehr A, Hochhaus A, Birndt S, et al. The Janus kinase 1/2 inhibitor ruxolitinib in COVID-19 with severe systemic hyperinflammation. Leukemia. 2020;34:1805–15.
doi: 10.1038/s41375-020-0891-0
Heidel F, Hochhaus A. Holding CoVID in check through JAK? The MPN-approved compound ruxolitinib as a potential strategy to treat SARS-CoV-2 induced systemic hyperinflammation. Leukemia. 2020;34:1723–5.
doi: 10.1038/s41375-020-0898-6
Koschmieder S, Jost E, Cornelissen C, Müller T, Schulze-Hagen M, Bickenbach J, et al. Favorable COVID-19 course despite significant comorbidities in a ruxolitinib-treated patient with primary myelofibrosis. Eur J Haematol. 2020;105:655–8.