The use of erythropoiesis-stimulating agents is safe and effective in the management of anaemia in myelofibrosis patients treated with ruxolitinib

Erythropoiesis-stimulating agents (ESAs) were combined with ruxolitinib in 59 anaemic myelofibrosis patients (93% with Dynamic International Prognostic Scoring System [DIPSS] intermediate-2/high risk; 52·5% transfusion-dependent). Anaemia response (AR) rate was 54% and 76% of patients responded at 5 years. A further 15% displayed minor improvement in anaemia and 78% of patients reduced spleen size. Endogenous erythropoietin levels <125 u/l correlated with a higher AR rate (63% vs. 20%, P = 0·008). No thrombotic events or other toxicities occurred. Overall survival was 62% at 4 years, influenced by DIPSS and transfusion dependency. ESAs seem effective in improving anaemia in ruxruxolitinib-treated myelofibrosis patients

Benefit-risk profile of cytoreductive drugs along with antiplatelet and antithrombotic therapy after transient ischemic attack or ischemic stroke in myeloproliferative neoplasms

We analyzed 597 patients with myeloproliferative neoplasms (MPN) who presented transient ischemic attacks (TIA, n = 270) or ischemic stroke (IS, n = 327). Treatment included aspirin, oral anticoagulants, and cytoreductive drugs. The composite incidence of recurrent TIA and IS, acute myocardial infarction (AMI), and cardiovascular (CV) death was 4.21 and 19.2%, respectively at one and five years after the index event, an estimate unexpectedly lower than reported in the general population. Patients tended to replicate the first clinical manifestation (hazard ratio, HR: 2.41 and 4.41 for recurrent TIA and IS, respectively); additional factors for recurrent TIA were previous TIA (HR: 3.40) and microvascular disturbances (HR: 2.30); for recurrent IS arterial hypertension (HR: 4.24) and IS occurrence after MPN diagnosis (HR: 4.47). CV mortality was predicted by age over 60 years (HR: 3.98), an index IS (HR: 3.61), and the occurrence of index events after MPN diagnosis (HR: 2.62). Cytoreductive therapy was a strong protective factor (HR: 0.24). The rate of major bleeding was similar to the general population (0.90 per 100 patient-years). In conclusion, the long-term clinical outcome after TIA and IS in MPN appears even more favorable than in the general population, suggesting an advantageous benefit-risk profile of antithrombotic and cytoreductive treatment

A Prognostic Model to Predict Ruxolitinib Discontinuation and Death in Patients with Myelofibrosis

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 &lt;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 &lt; 100 × 109/L, Hb &lt; 10 g/dL, primary MF, absence of spleen response at 3 months and ruxolitinib starting dose &lt;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

Ruxolitinib in cytopenic myelofibrosis: Response, toxicity, drug discontinuation, and outcome

Background: Patients with cytopenic myelofibrosis (MF) have more limited therapeutic options and poorer prognoses compared with patients with the myeloproliferative phenotype. Aims and methods: Prognostic correlates of cytopenic phenotype were explored in 886 ruxolitinib-treated patients with primary/secondary MF (PMF/SMF) included in the RUX-MF retrospective study. Cytopenia was defined as: leukocyte count &lt;4&nbsp;×&nbsp;109 /L and/or hemoglobin &lt;11/&lt;10&nbsp;g/dL (males/females) and/or platelets &lt;100&nbsp;×&nbsp;109 /L. Results: Overall, 407 (45.9%) patients had a cytopenic MF, including 249 (52.4%) with PMF. In multivariable analysis, high molecular risk mutations (p&nbsp;=&nbsp;.04), intermediate 2/high Dynamic International Prognostic Score System (p&nbsp;&lt;&nbsp;.001) and intermediate 2/high Myelofibrosis Secondary to Polycythemia Vera and Essential Thrombocythemia Prognostic Model (p&nbsp;&lt;&nbsp;.001) remained associated with cytopenic MF in the overall cohort, PMF, and SMF, respectively. Patients with cytopenia received lower average ruxolitinib at the starting (25.2&nbsp;mg/day vs. 30.2&nbsp;mg/day, p&nbsp;&lt;&nbsp;.001) and overall doses (23.6&nbsp;mg/day vs. 26.8&nbsp;mg/day, p&nbsp;&lt;&nbsp;.001) and achieved lower rates of spleen (26.5% vs. 34.1%, p&nbsp;=&nbsp;.04) and symptom (59.8% vs. 68.8%, p&nbsp;=&nbsp;.008) responses at 6&nbsp;months compared with patients with the proliferative phenotype. Patients with cytopenia also had higher rates of thrombocytopenia at 3&nbsp;months (31.1% vs. 18.8%, p&nbsp;&lt;&nbsp;.001) but lower rates of anemia (65.6% vs. 57.7%, p&nbsp;=&nbsp;.02 at 3&nbsp;months and 56.6% vs. 23.9% at 6&nbsp;months, p&nbsp;&lt;&nbsp;.001). After competing risk analysis, the cumulative incidence of ruxolitinib discontinuation at 5&nbsp;years was 57% and 38% in patients with cytopenia and the proliferative phenotype (p&nbsp;&lt;&nbsp;.001), whereas cumulative incidence of leukemic transformation was similar (p&nbsp;=&nbsp;.06). In Cox regression analysis adjusted for Dynamic International Prognostic Score System score, survival was significantly shorter in patients with cytopenia (p&nbsp;&lt;&nbsp;.001). Conclusions: Cytopenic MF has a lower probability of therapeutic success with ruxolitinib as monotherapy and worse outcome. These patients should be considered for alternative therapeutic strategies