Clinical outcomes of ruxolitinib treatment in 595 intermediate‐1 risk patients with myelofibrosis: The RUX‐MF Real‐World Study

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 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, U2AF1 Q157 ) 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 10 9 /L: n = 43; white blood cells <4 x 10 9 /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.