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, Costanza Bosi, Roberto Latagliata, Ambra Di Veroli, Luigi Scaffidi, Federico de Marchi, Elisa CerquiBarbara Anaclerico, 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, Massimo Breccia

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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 <200×109/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.

Original languageEnglish
Pages (from-to)79073-79086
Number of pages14
JournalOncotarget
Volume8
Issue number45
DOIs
Publication statusPublished - Oct 3 2017

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Primary Myelofibrosis
Spleen
Risk Adjustment
Splenomegaly
Hematology
Therapeutics
INCB018424
Platelet Count
Proportional Hazards Models
Survival

Keywords

  • Journal Article

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Baseline factors associated with response to ruxolitinib : an independent study on 408 patients with myelofibrosis. / 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; Bacchi Reggiani, Maria Letizia; Cavo, Michele; Vianelli, Nicola; Breccia, Massimo.

In: Oncotarget, Vol. 8, No. 45, 03.10.2017, p. 79073-79086.

Research output: Contribution to journalArticle

Palandri, F, Palumbo, GA, Bonifacio, M, Tiribelli, M, Benevolo, G, Martino, B, Abruzzese, E, D'Adda, M, Polverelli, N, Bergamaschi, M, Tieghi, A, Cavazzini, F, Ibatici, A, Crugnola, M, Bosi, C, Latagliata, R, Di Veroli, A, Scaffidi, L, de Marchi, F, Cerqui, E, Anaclerico, B, De Matteis, G, Spinsanti, M, Sabattini, E, Catani, L, Aversa, F, Di Raimondo, F, Vitolo, U, Lemoli, RM, Fanin, R, Merli, F, Russo, D, Cuneo, A, Bacchi Reggiani, ML, Cavo, M, Vianelli, N & Breccia, M 2017, 'Baseline factors associated with response to ruxolitinib: an independent study on 408 patients with myelofibrosis', Oncotarget, vol. 8, no. 45, pp. 79073-79086. https://doi.org/10.18632/oncotarget.18674
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 ; Bacchi Reggiani, Maria Letizia ; Cavo, Michele ; Vianelli, Nicola ; Breccia, Massimo. / Baseline factors associated with response to ruxolitinib : an independent study on 408 patients with myelofibrosis. In: Oncotarget. 2017 ; Vol. 8, No. 45. pp. 79073-79086.
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AU - Palandri, Francesca

AU - Palumbo, Giuseppe Alberto

AU - Bonifacio, Massimiliano

AU - Tiribelli, Mario

AU - Benevolo, Giulia

AU - Martino, Bruno

AU - Abruzzese, Elisabetta

AU - D'Adda, Mariella

AU - Polverelli, Nicola

AU - Bergamaschi, Micaela

AU - Tieghi, Alessia

AU - Cavazzini, Francesco

AU - Ibatici, Adalberto

AU - Crugnola, Monica

AU - Bosi, Costanza

AU - Latagliata, Roberto

AU - Di Veroli, Ambra

AU - Scaffidi, Luigi

AU - de Marchi, Federico

AU - Cerqui, Elisa

AU - Anaclerico, Barbara

AU - De Matteis, Giovanna

AU - Spinsanti, Marco

AU - Sabattini, Elena

AU - Catani, Lucia

AU - Aversa, Franco

AU - Di Raimondo, Francesco

AU - Vitolo, Umberto

AU - Lemoli, Roberto Massimo

AU - Fanin, Renato

AU - Merli, Francesco

AU - Russo, Domenico

AU - Cuneo, Antonio

AU - Bacchi Reggiani, Maria Letizia

AU - Cavo, Michele

AU - Vianelli, Nicola

AU - Breccia, Massimo

PY - 2017/10/3

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N2 - 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 <200×109/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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