Oncotarget

Clinical Research Papers:

Baseline factors associated with response to ruxolitinib: an independent study on 408 patients with myelofibrosis

Francesca Palandri _, Giuseppe Alberto Palumbo, Massimiliano Bonifacio, Mario Tiribelli, Giulia Benevolo, Bruno Martino, Elisabetta Abruzzese, Mariella D’Adda, Nicola Polverelli, Micaela Bergamaschi, Alessia Tieghi, Francesco Cavazzini, Adalberto Ibatici, Monica Crugnola Monica Crugnola, Costanza Bosi, Roberto Latagliata, Ambra Di Veroli, Luigi Scaffidi, Federico de Marchi, Elisa Cerqui, Barbara Anaclerico, Giovanna De Matteis, Giovanna De Matteis, Marco Spinsanti, Elena Sabattini, Lucia Catani, Franco Aversa, Francesco Di Raimondo, Umberto Vitolo, Roberto Massimo Lemoli, Renato Fanin, Francesco Merli, Domenico Russo, Antonio Cuneo, Maria Letizia Bacchi Reggiani, Michele Cavo, Nicola Vianelli and Massimo Breccia

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Oncotarget. 2017; 8:79073-79086. https://doi.org/10.18632/oncotarget.18674

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Abstract

Francesca Palandri1, Giuseppe Alberto Palumbo2, Massimiliano Bonifacio3, Mario Tiribelli4, Giulia Benevolo5, Bruno Martino6, Elisabetta Abruzzese7, Mariella D’Adda8, Nicola Polverelli9, Micaela Bergamaschi10, Alessia Tieghi11, Francesco Cavazzini12, Adalberto Ibatici13, Monica Crugnola14, Costanza Bosi15, Roberto Latagliata16, Ambra Di Veroli17, Luigi Scaffidi3, Federico de Marchi4, Elisa Cerqui8, Barbara Anaclerico18, Giovanna De Matteis19, Marco Spinsanti1, Elena Sabattini1, Lucia Catani1, Franco Aversa14, Francesco Di Raimondo2, Umberto Vitolo5, Roberto Massimo Lemoli10, Renato Fanin4, Francesco Merli11, Domenico Russo9, Antonio Cuneo12, Maria Letizia Bacchi Reggiani20, Michele Cavo1, Nicola Vianelli1 and Massimo Breccia16

1Institute of Hematology “L. and A. Seràgnoli”, Sant'Orsola-Malpighi University Hospital, Bologna, Italy

2Division of Hematology, AOU 'Policlinico-V.Emanuele', Catania, Italy

3Department of Hematology, University of Verona, Verona, Italy

4Division of Hematology and BMT, Azienda Sanitaria Universitaria Integrata di Udine, Udine, Italy

5Division of Hematology, Città della Salute e della Scienza Hospital, Torino, Italy

6Division of Hematology, Azienda Ospedaliera 'Bianchi Melacrino Morelli', Reggio Calabria, Italy

7Division of Hematology, Ospedale S. Eugenio, Roma, Italy

8Division of Hematology, ASST Spedali Civili di Brescia, Brescia, Italy

9Unit of Blood Diseases and Stem Cell Transplantation, ASST Spedali Civili di Brescia, Brescia, Italy

10Division of Hematology, IRCCS AOU San Martino-IST, Genova, Italy

11Department of Hematology, A.O. Arcispedale Santa Maria Nuova – IRCCS, Reggio Emilia, Italy

12Division of Hematology, University of Ferrara, Ferrara, Italy

13Division of Hematology and Bone Marrow Transplant, IRCCS San Martino-IST, Genova, Italy

14Division of Hematology, AOU of Parma, Parma, Italy

15Department of Hematology and Bone Marrow Transplantation, A.O. of Piacenza, Italy

16Division of Cellular Biotechnologies and Hematology, University Sapienza, Roma, Italy

17Division of Hematology, Policlinico Tor Vergata, Roma, Italy

18Division of Hematology, Ospedale S. Giovanni, Roma, Italy

19Department of Life and Reproduction Sciences, Section of Clinical Biochemistry, University of Verona, Verona, Italy

20Division of Cardiology, University of Bologna, Bologna, Italy

Correspondence to:

Francesca Palandri, email: francesca.palandri@unibo.it

Keywords: myelofibrosis, splenomegaly, response, ruxolitinib, predictive factors

Received: March 29, 2017     Accepted: May 15, 2017     Published: June 27, 2017

ABSTRACT

In patients with Myelofibrosis (MF) treated with ruxolitinib (RUX), the response is unpredictable at therapy start. We retrospectively evaluated the impact of clinical/laboratory factors on responses in 408 patients treated with RUX according to prescribing obligations in 18 Italian Hematology Centers. At 6 months, 114 out of 327 (34.9%) evaluable patients achieved a spleen response. By multivariable Cox proportional hazard regression model, pre-treatment factors negatively correlating with spleen response were: high/intermediate-2 IPSS risk (p=0.024), large splenomegaly (p=0.017), transfusion dependency (p=0.022), platelet count <200x109/l (p=0.028), and a time-interval between MF diagnosis and RUX start >2 years (p=0.048). Also, patients treated with higher (≥10 mg BID) average RUX doses in the first 12 weeks achieved higher response rates (p=0.019). After adjustment for IPSS risk, patients in spleen response at 6 months showed only a trend for better survival compared to non-responders. At 6 months, symptoms response was achieved by 85.5% of 344 evaluable patients; only a higher (>20) Total Symptom Score significantly correlated with lower probability of response (p<0.001). Increased disease severity, a delay in RUX start and titrated doses <10 mg BID were associated with patients achievinglower response rates. An early treatment and higher RUX doses may achieve better therapeutic results.


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PII: 18674