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

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.

Data di pubblicazione: 2017
Titolo: Baseline factors associated with response to ruxolitinib: An independent study on 408 patients with myelofibrosis
Autori: Palandri, Francesca; Palumbo, Giuseppe Alberto; Bonifacio, Massimiliano; Tiribelli, Mario; Benevolo, Giulia; Martino, Bruno; Abruzzese, Elisabetta; D'Adda, Mariella; Polverelli, Nicola; Bergamaschi, Micaela; Tieghi, Alessia; Cavazzini, Francesco; Ibatici, Adalberto; Crugnola, Monica; Bosi, Costanza; Latagliata, Roberto; Di Veroli, Ambra; Scaffidi, Luigi; de Marchi, Federico; Cerqui, Elisa; Anaclerico, Barbara; De Matteis, Giovanna; Spinsanti, Marco; Sabattini, Elena; Catani, Lucia; Aversa, Franco; Di Raimondo, Francesco; Vitolo, Umberto; Lemoli, Roberto Massimo; Fanin, Renato; Merli, Francesco; Russo, Domenico; Cuneo, Antonio; Reggiani, Maria Letizia Bacchi; Cavo, Michele; Vianelli, Nicola; Breccia, Massimo
Rivista: ONCOTARGET
Keywords: Myelofibrosis; Predictive factors; Response; Ruxolitinib; Splenomegaly; Oncology
Abstract in inglese: 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.
Digital Object Identifier (DOI): 10.18632/oncotarget.18674
Handle: http://hdl.handle.net/11392/2382548
Appare nelle tipologie:03.1 Articolo su rivista

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