Ruxolitinib (RUX) is extensively used in myelofibrosis (MF). Despite its early efficacy, most patients lose response over time and, after discontinuation, have a worse overall survival (OS). Currently, response criteria able to predict OS in RUX-treated patients are lacking, leading to uncertainty regarding the switch to second-line treatments. In this study, we investigated predictors of survival collected after 6 months of RUX in 209 MF patients participating in the real-world ambispective observational RUXOREL-MF study (NCT03959371). Multivariable analysis identified the following risk factors: (1) RUX dose,20 mg twice daily at baseline, months 3 and 6 (hazard ratio [HR], 1.79; 95% confidence interval [CI], 1.07-3.00; P 5.03), (2) palpable spleen length reduction from baseline #30% at months 3 and 6 (HR, 2.26; 95% CI, 1.40-3.65; P 5.0009), (3) red blood cell (RBC) transfusion need at months 3 and/or 6 (HR, 1.66; 95% CI, 0.95-2.88; P 5.07), and (4) RBC transfusion need at all time points (ie, baseline and months 3 and 6; HR, 2.32; 95% CI, 1.19-4.54; P 5.02). Hence, we developed a prognostic model, named Response to Ruxolitinib After 6 Months (RR6), dissecting 3 risk categories: low (median OS, not reached), intermediate (median OS, 61 months; 95% CI, 43-80), and high (median OS, 33 months; 95% CI, 21-50). The RR6 model was validated and confirmed in an external cohort comprised of 40 MF patients. In conclusion, the RR6 prognostic model allows for the early identification of RUX-treated MF patients with impaired survival who might benefit from a prompt treatment shift.

A prognostic model to predict survival after 6 months of ruxolitinib in patients with myelofibrosis

Mora B.;Passamonti F.
2022-01-01

Abstract

Ruxolitinib (RUX) is extensively used in myelofibrosis (MF). Despite its early efficacy, most patients lose response over time and, after discontinuation, have a worse overall survival (OS). Currently, response criteria able to predict OS in RUX-treated patients are lacking, leading to uncertainty regarding the switch to second-line treatments. In this study, we investigated predictors of survival collected after 6 months of RUX in 209 MF patients participating in the real-world ambispective observational RUXOREL-MF study (NCT03959371). Multivariable analysis identified the following risk factors: (1) RUX dose,20 mg twice daily at baseline, months 3 and 6 (hazard ratio [HR], 1.79; 95% confidence interval [CI], 1.07-3.00; P 5.03), (2) palpable spleen length reduction from baseline #30% at months 3 and 6 (HR, 2.26; 95% CI, 1.40-3.65; P 5.0009), (3) red blood cell (RBC) transfusion need at months 3 and/or 6 (HR, 1.66; 95% CI, 0.95-2.88; P 5.07), and (4) RBC transfusion need at all time points (ie, baseline and months 3 and 6; HR, 2.32; 95% CI, 1.19-4.54; P 5.02). Hence, we developed a prognostic model, named Response to Ruxolitinib After 6 Months (RR6), dissecting 3 risk categories: low (median OS, not reached), intermediate (median OS, 61 months; 95% CI, 43-80), and high (median OS, 33 months; 95% CI, 21-50). The RR6 model was validated and confirmed in an external cohort comprised of 40 MF patients. In conclusion, the RR6 prognostic model allows for the early identification of RUX-treated MF patients with impaired survival who might benefit from a prompt treatment shift.
2022
Humans; Nitriles; Prognosis; Pyrazoles; Pyrimidines; Retrospective Studies; Primary Myelofibrosis
Maffioli, M.; Mora, B.; Ball, S.; Iurlo, A.; Elli, E. M.; Finazzi, M. C.; Polverelli, N.; Rumi, E.; Caramella, M.; Carraro, M. C.; D'Adda, M.; Molteni, A.; Sissa, C.; Lunghi, F.; Vismara, A.; Ubezio, M.; Guidetti, A.; Caberlon, S.; Anghilieri, M.; Komrokji, R.; Cattaneo, D.; Della Porta, M. G.; Giorgino, T.; Bertu, L.; Brociner, M.; Kuykendall, A.; Passamonti, F.
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11383/2143458
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