Most patients with myelofibrosis (MF) discontinue ruxolitinib (JAK1/JAK2 inhibitor) in the first 5 years of therapy due to therapy failure. As the therapeutic possibilities of MF are expanding, it is critical to identify patients predisposed to early ruxolitinib monotherapy failure and worse outcomes. We investigated predictors of early ruxolitinib discontinuation and death on therapy in 889 patients included in the "RUX-MF" retrospective study. Overall, 172 patients were alive on ruxolitinib after ≥5 years (long-term ruxolitinib, LTR), 115 patients were alive but off ruxolitinib after ≥5 yrs (short-term RUX, STR), and 123 patients died while on ruxolitinib after <5 yrs (early death on ruxolitinib, EDR). The cumulative incidence of the blast phase was similar in LTR and STR patients (p = 0.08). Overall survival (OS) was significantly longer in LTR pts (p = 0.002). In multivariate analysis, PLT < 100 × 109/L, Hb < 10 g/dL, primary MF, absence of spleen response at 3 months and ruxolitinib starting dose <10 mg BID were associated with higher probability of STR. Assigning one point to each significant variable, a prognostic model for STR (STR-PM) was built, and three groups were identified: low (score 0-1), intermediate (score 2), and high risk (score ≥ 3). The STR-PM may identify patients at higher risk of failure with ruxolitinib monotherapy who should be considered for alternative frontline strategies.
Keywords: myelofibrosis; prognostic model; ruxolitinib.