Background: Ruxolitinib (RUX) is a JAK1/2 inhibitor approved for the therapy of myelofibrosis (MF) based on clinical trials including only intermediate2-high risk (INT2/HIGH) patients. However, RUX is commonly used in intermediate-1 (INT1) patients, with scarce information on responses and outcome. Methods: The authors investigated the benefit of RUX in 1055 MF patients, included in the ``RUX-MF{''} retrospective study. Results: At baseline (BL), 595 (56.2\%) patients were at INT1-risk according to DIPSS (PMF) or MYSEC-PM (SMF). The spleen was palpable at <5 cm, between 5 and 10 cm, and >10 cm below costal margin in 5.9\%, 47.4\%, and 39.7\% of patients, respectively; 300 (54.1\%) were highly symptomatic (total symptom score >= 20). High-molecular-risk (HMR) mutations (IDH1/2, ASXL-1, SRSF2, EZH2, U2AF1Q157) were detected in 77/167 patients. A total of 101 (19.2\%) patients had >= 1 cytopenia (Hb < 10 g/dL: n.36; PLT <100 x 109/L: n = 43; white blood cells <4 x 109/L: n = 40). After 6 months on RUX, IWG-MRT-defined spleen and symptoms response rates were 26.8\% and 67.9\%, respectively. In univariate analysis, predictors of SR at 6 months were no HMR mutations odds ratio {[}OR], 2.0, p = .05], no cytopenia (OR, 2.10; p = .01), and blasts <1\% (OR, 1.91; p = .01). In multivariate analysis, absence of HMR maintained a significant association (OR, 2.1 {[}1.12-3.76]; p = .01). Conclusions: In INT1 patients, responses were more frequent and durable, whereas toxicity rates were lower compared to INT2/high-risk patients. Presence of HMR mutations, cytopenia, and peripheral blasts identified less-responsive INT1 patients, who may benefit for alternative therapeutic strategies.
Clinical outcomes of ruxolitinib treatment in 595 intermediate-1 risk patients with myelofibrosis: The RUX-MF Real-World Study / Palandri, Francesca; Elli, Elena M.; Morsia, Erika; Benevolo, Giulia; Tiribelli, Mario; Beggiato, Eloise; Bonifacio, Massimiliano; Farina, Mirko; Martino, Bruno; Caocci, Giovanni; Pugliese, Novella; Tieghi, Alessia; Crugnola, Monica; Binotto, Gianni; Cavazzini, Francesco; Abruzzese, Elisabetta; Iurlo, Alessandra; Isidori, Alessandro; Bosi, Costanza; Guglielmana, Veronica; Venturi, Marta; Dedola, Alessandra; Loffredo, Michele; Fontana, Gabriele; Duminuco, Andrea; Moioli, Alessia; Tosoni, Luca; Scalzulli, Emilia; Cattaneo, Daniele; Lemoli, Roberto M.; Cilloni, Daniela; Bocchia, Monica; Pane, Fabrizio; Heidel, Florian H.; Vianelli, Nicola; Cavo, Michele; Palumbo, Giuseppe A.; Branzanti, Filippo; Breccia, Massimo. - In: CANCER. - ISSN 0008-543X. - (2024). [10.1002/cncr.35489]
Clinical outcomes of ruxolitinib treatment in 595 intermediate-1 risk patients with myelofibrosis: The RUX-MF Real-World Study
Scalzulli, Emilia;Breccia, Massimo
2024
Abstract
Background: Ruxolitinib (RUX) is a JAK1/2 inhibitor approved for the therapy of myelofibrosis (MF) based on clinical trials including only intermediate2-high risk (INT2/HIGH) patients. However, RUX is commonly used in intermediate-1 (INT1) patients, with scarce information on responses and outcome. Methods: The authors investigated the benefit of RUX in 1055 MF patients, included in the ``RUX-MF{''} retrospective study. Results: At baseline (BL), 595 (56.2\%) patients were at INT1-risk according to DIPSS (PMF) or MYSEC-PM (SMF). The spleen was palpable at <5 cm, between 5 and 10 cm, and >10 cm below costal margin in 5.9\%, 47.4\%, and 39.7\% of patients, respectively; 300 (54.1\%) were highly symptomatic (total symptom score >= 20). High-molecular-risk (HMR) mutations (IDH1/2, ASXL-1, SRSF2, EZH2, U2AF1Q157) were detected in 77/167 patients. A total of 101 (19.2\%) patients had >= 1 cytopenia (Hb < 10 g/dL: n.36; PLT <100 x 109/L: n = 43; white blood cells <4 x 109/L: n = 40). After 6 months on RUX, IWG-MRT-defined spleen and symptoms response rates were 26.8\% and 67.9\%, respectively. In univariate analysis, predictors of SR at 6 months were no HMR mutations odds ratio {[}OR], 2.0, p = .05], no cytopenia (OR, 2.10; p = .01), and blasts <1\% (OR, 1.91; p = .01). In multivariate analysis, absence of HMR maintained a significant association (OR, 2.1 {[}1.12-3.76]; p = .01). Conclusions: In INT1 patients, responses were more frequent and durable, whereas toxicity rates were lower compared to INT2/high-risk patients. Presence of HMR mutations, cytopenia, and peripheral blasts identified less-responsive INT1 patients, who may benefit for alternative therapeutic strategies.I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.
