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

2024-01-01

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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.