Epidemiology, outcome, and risk factors for infectious complications in myelofibrosis patients receiving ruxolitinib: A multicenter study on 446 patients

Nicola Polverelli, Giuseppe A Palumbo, Gianni Binotto, Elisabetta Abruzzese, Giulia Benevolo, Micaela Bergamaschi, Alessia Tieghi, Massimiliano Bonifacio, Massimo Breccia, Lucia Catani, Mario Tiribelli, Mariella D'Adda, Nicola Sgherza, Alessandro Isidori, Francesco Cavazzini, Bruno Martino, Roberto Latagliata, Monica Crugnola, Florian Heidel, Costanza BosiAdalberto Ibatici, Francesco Soci, Domenico Penna, Luigi Scaffidi, Franco Aversa, Roberto M Lemoli, Umberto Vitolo, Antonio Cuneo, Domenico Russo, Michele Cavo, Nicola Vianelli, Francesca Palandri

Research output: Contribution to journalArticle

Abstract

Infections represent one of the major concerns regarding the utilization of ruxolitinib (RUX) in patients with myelofibrosis. With the aim to investigate epidemiology, outcome and risk factors for infections in RUX-exposed patients, we collected clinical and laboratory data of 446 myelofibrosis patients treated with RUX between June 2011 and November 2016 in 23 European Hematology Centers. After a median RUX exposure of 23.5 months (range, 1-56), 123 patients (28%) experienced 161 infectious events (grades 3-4 32%, fatal 9%), for an incidence rate of 17 cases per 100 pts/y. The rate of infections tended to decrease over time: 14% of patients developed the first infection within 6 months, 5% between 6 and 12 months, 3.7% between 12 and 18 months, 3.4% between 18 and 24 months, and 7.9% thereafter (P < .0001). Respiratory tract infections were more frequently observed (81 events, 50%), and bacteria were the most frequent etiological agents (68.9%). However, also viral (14.9%) and fungal infections (2.5%) were observed. In multivariate analysis, previous infectious event (HR 2.54; 95% CI, 1.51-4.28; P = .0005) and high international prognostic score system category (IPSS) (HR 1.53; 95% CI, 1.07-2.20; P = .021) significantly correlated with higher infectious risk. On the contrary, spleen reduction ≥50% from baseline after 3 months of treatment (P = .02) was associated with better infection-free survival. Taken together, these findings reinforce the concept of disease severity as the most important risk factor for infections, and describe, for the first time, that a positive therapeutic effect in reducing splenomegaly may also reduce subsequent infectious complications.

Original languageEnglish
JournalHematological Oncology
DOIs
Publication statusE-pub ahead of print - Apr 6 2018

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Primary Myelofibrosis
Multicenter Studies
Epidemiology
Infection
Mycoses
Splenomegaly
Therapeutic Uses
Hematology
Virus Diseases
Respiratory Tract Infections
INCB018424
Spleen
Multivariate Analysis
Bacteria
Survival
Incidence

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Epidemiology, outcome, and risk factors for infectious complications in myelofibrosis patients receiving ruxolitinib : A multicenter study on 446 patients. / Polverelli, Nicola; Palumbo, Giuseppe A; Binotto, Gianni; Abruzzese, Elisabetta; Benevolo, Giulia; Bergamaschi, Micaela; Tieghi, Alessia; Bonifacio, Massimiliano; Breccia, Massimo; Catani, Lucia; Tiribelli, Mario; D'Adda, Mariella; Sgherza, Nicola; Isidori, Alessandro; Cavazzini, Francesco; Martino, Bruno; Latagliata, Roberto; Crugnola, Monica; Heidel, Florian; Bosi, Costanza; Ibatici, Adalberto; Soci, Francesco; Penna, Domenico; Scaffidi, Luigi; Aversa, Franco; Lemoli, Roberto M; Vitolo, Umberto; Cuneo, Antonio; Russo, Domenico; Cavo, Michele; Vianelli, Nicola; Palandri, Francesca.

In: Hematological Oncology, 06.04.2018.

Research output: Contribution to journalArticle

Polverelli, N, Palumbo, GA, Binotto, G, Abruzzese, E, Benevolo, G, Bergamaschi, M, Tieghi, A, Bonifacio, M, Breccia, M, Catani, L, Tiribelli, M, D'Adda, M, Sgherza, N, Isidori, A, Cavazzini, F, Martino, B, Latagliata, R, Crugnola, M, Heidel, F, Bosi, C, Ibatici, A, Soci, F, Penna, D, Scaffidi, L, Aversa, F, Lemoli, RM, Vitolo, U, Cuneo, A, Russo, D, Cavo, M, Vianelli, N & Palandri, F 2018, 'Epidemiology, outcome, and risk factors for infectious complications in myelofibrosis patients receiving ruxolitinib: A multicenter study on 446 patients', Hematological Oncology. https://doi.org/10.1002/hon.2509
Polverelli, Nicola ; Palumbo, Giuseppe A ; Binotto, Gianni ; Abruzzese, Elisabetta ; Benevolo, Giulia ; Bergamaschi, Micaela ; Tieghi, Alessia ; Bonifacio, Massimiliano ; Breccia, Massimo ; Catani, Lucia ; Tiribelli, Mario ; D'Adda, Mariella ; Sgherza, Nicola ; Isidori, Alessandro ; Cavazzini, Francesco ; Martino, Bruno ; Latagliata, Roberto ; Crugnola, Monica ; Heidel, Florian ; Bosi, Costanza ; Ibatici, Adalberto ; Soci, Francesco ; Penna, Domenico ; Scaffidi, Luigi ; Aversa, Franco ; Lemoli, Roberto M ; Vitolo, Umberto ; Cuneo, Antonio ; Russo, Domenico ; Cavo, Michele ; Vianelli, Nicola ; Palandri, Francesca. / Epidemiology, outcome, and risk factors for infectious complications in myelofibrosis patients receiving ruxolitinib : A multicenter study on 446 patients. In: Hematological Oncology. 2018.
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abstract = "Infections represent one of the major concerns regarding the utilization of ruxolitinib (RUX) in patients with myelofibrosis. With the aim to investigate epidemiology, outcome and risk factors for infections in RUX-exposed patients, we collected clinical and laboratory data of 446 myelofibrosis patients treated with RUX between June 2011 and November 2016 in 23 European Hematology Centers. After a median RUX exposure of 23.5 months (range, 1-56), 123 patients (28{\%}) experienced 161 infectious events (grades 3-4 32{\%}, fatal 9{\%}), for an incidence rate of 17 cases per 100 pts/y. The rate of infections tended to decrease over time: 14{\%} of patients developed the first infection within 6 months, 5{\%} between 6 and 12 months, 3.7{\%} between 12 and 18 months, 3.4{\%} between 18 and 24 months, and 7.9{\%} thereafter (P < .0001). Respiratory tract infections were more frequently observed (81 events, 50{\%}), and bacteria were the most frequent etiological agents (68.9{\%}). However, also viral (14.9{\%}) and fungal infections (2.5{\%}) were observed. In multivariate analysis, previous infectious event (HR 2.54; 95{\%} CI, 1.51-4.28; P = .0005) and high international prognostic score system category (IPSS) (HR 1.53; 95{\%} CI, 1.07-2.20; P = .021) significantly correlated with higher infectious risk. On the contrary, spleen reduction ≥50{\%} from baseline after 3 months of treatment (P = .02) was associated with better infection-free survival. Taken together, these findings reinforce the concept of disease severity as the most important risk factor for infections, and describe, for the first time, that a positive therapeutic effect in reducing splenomegaly may also reduce subsequent infectious complications.",
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T1 - Epidemiology, outcome, and risk factors for infectious complications in myelofibrosis patients receiving ruxolitinib

T2 - A multicenter study on 446 patients

AU - Polverelli, Nicola

AU - Palumbo, Giuseppe A

AU - Binotto, Gianni

AU - Abruzzese, Elisabetta

AU - Benevolo, Giulia

AU - Bergamaschi, Micaela

AU - Tieghi, Alessia

AU - Bonifacio, Massimiliano

AU - Breccia, Massimo

AU - Catani, Lucia

AU - Tiribelli, Mario

AU - D'Adda, Mariella

AU - Sgherza, Nicola

AU - Isidori, Alessandro

AU - Cavazzini, Francesco

AU - Martino, Bruno

AU - Latagliata, Roberto

AU - Crugnola, Monica

AU - Heidel, Florian

AU - Bosi, Costanza

AU - Ibatici, Adalberto

AU - Soci, Francesco

AU - Penna, Domenico

AU - Scaffidi, Luigi

AU - Aversa, Franco

AU - Lemoli, Roberto M

AU - Vitolo, Umberto

AU - Cuneo, Antonio

AU - Russo, Domenico

AU - Cavo, Michele

AU - Vianelli, Nicola

AU - Palandri, Francesca

N1 - Copyright © 2018 John Wiley & Sons, Ltd.

PY - 2018/4/6

Y1 - 2018/4/6

N2 - Infections represent one of the major concerns regarding the utilization of ruxolitinib (RUX) in patients with myelofibrosis. With the aim to investigate epidemiology, outcome and risk factors for infections in RUX-exposed patients, we collected clinical and laboratory data of 446 myelofibrosis patients treated with RUX between June 2011 and November 2016 in 23 European Hematology Centers. After a median RUX exposure of 23.5 months (range, 1-56), 123 patients (28%) experienced 161 infectious events (grades 3-4 32%, fatal 9%), for an incidence rate of 17 cases per 100 pts/y. The rate of infections tended to decrease over time: 14% of patients developed the first infection within 6 months, 5% between 6 and 12 months, 3.7% between 12 and 18 months, 3.4% between 18 and 24 months, and 7.9% thereafter (P < .0001). Respiratory tract infections were more frequently observed (81 events, 50%), and bacteria were the most frequent etiological agents (68.9%). However, also viral (14.9%) and fungal infections (2.5%) were observed. In multivariate analysis, previous infectious event (HR 2.54; 95% CI, 1.51-4.28; P = .0005) and high international prognostic score system category (IPSS) (HR 1.53; 95% CI, 1.07-2.20; P = .021) significantly correlated with higher infectious risk. On the contrary, spleen reduction ≥50% from baseline after 3 months of treatment (P = .02) was associated with better infection-free survival. Taken together, these findings reinforce the concept of disease severity as the most important risk factor for infections, and describe, for the first time, that a positive therapeutic effect in reducing splenomegaly may also reduce subsequent infectious complications.

AB - Infections represent one of the major concerns regarding the utilization of ruxolitinib (RUX) in patients with myelofibrosis. With the aim to investigate epidemiology, outcome and risk factors for infections in RUX-exposed patients, we collected clinical and laboratory data of 446 myelofibrosis patients treated with RUX between June 2011 and November 2016 in 23 European Hematology Centers. After a median RUX exposure of 23.5 months (range, 1-56), 123 patients (28%) experienced 161 infectious events (grades 3-4 32%, fatal 9%), for an incidence rate of 17 cases per 100 pts/y. The rate of infections tended to decrease over time: 14% of patients developed the first infection within 6 months, 5% between 6 and 12 months, 3.7% between 12 and 18 months, 3.4% between 18 and 24 months, and 7.9% thereafter (P < .0001). Respiratory tract infections were more frequently observed (81 events, 50%), and bacteria were the most frequent etiological agents (68.9%). However, also viral (14.9%) and fungal infections (2.5%) were observed. In multivariate analysis, previous infectious event (HR 2.54; 95% CI, 1.51-4.28; P = .0005) and high international prognostic score system category (IPSS) (HR 1.53; 95% CI, 1.07-2.20; P = .021) significantly correlated with higher infectious risk. On the contrary, spleen reduction ≥50% from baseline after 3 months of treatment (P = .02) was associated with better infection-free survival. Taken together, these findings reinforce the concept of disease severity as the most important risk factor for infections, and describe, for the first time, that a positive therapeutic effect in reducing splenomegaly may also reduce subsequent infectious complications.

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DO - 10.1002/hon.2509

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JF - Hematological Oncology

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