Project description:Myelofibrosis (MF), a Philadelphia chromosome-negative myeloproliferative neoplasm, is characterized by progressive bone marrow fibrosis and ineffective hematopoiesis. Clinical hallmarks include splenomegaly, anemia, and debilitating symptoms. In 2 randomized phase III studies, the Janus kinase (JAK) 1/JAK2 inhibitor ruxolitinib significantly improved splenomegaly and disease-related symptoms compared with placebo (Controlled Myelofibrosis Study with Oral JAK Inhibitor Treatment [COMFORT-I]) or best available therapy (COMFORT-II) in patients with intermediate-2 or high-risk MF. Although ruxolitinib therapy was associated with dose-dependent anemia and thrombocytopenia, these adverse events rarely led to treatment discontinuation. This update of the clinical effects of ruxolitinib in patients with MF was based on original articles and meeting abstracts published after the primary publication of the COMFORT trials in March 2012. Long-term follow-up data from the COMFORT trials and clinical experience with ruxolitinib in unselected patient populations suggest that improvement of splenomegaly and symptoms is durable. Patients benefit from ruxolitinib therapy across subgroups defined by age, MF type, risk category, performance status, JAK2 V617F mutation status, extent of splenomegaly, or presence of cytopenias. In COMFORT-I, platelet counts stabilized with dose adjustments, and hemoglobin levels gradually recovered to slightly below baseline after the first 8 to 12 weeks of therapy. After initial increases, the need for red blood cell transfusions decreased to a level similar to that found in the placebo group. The 2-year follow-up data from the COMFORT trials suggest that patients with intermediate-2 or high-risk MF receiving ruxolitinib therapy may have improved survival compared with those receiving no (placebo) or traditional therapy.

| S-EPMC5556922 | biostudies-other

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

Project description:BackgroundRuxolitinib (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.MethodsThe authors investigated the benefit of RUX in 1055 MF patients, included in the "RUX-MF" retrospective study.ResultsAt 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).ConclusionsIn 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.

| S-EPMC11585342 | biostudies-literature

Real-World Assessment of Clinical Outcomes in Patients with Lower-Risk Myelofibrosis Receiving Treatment with Ruxolitinib.

Project description:Few trial-based assessments of ruxolitinib in patients with lower-risk myelofibrosis (MF) have been conducted, and no studies have made such assessments in a real-world population. We assessed changes in spleen size and constitutional symptoms during ruxolitinib treatment using a retrospective, observational review of anonymized US medical record data of patients diagnosed with IPSS low-risk (n = 25) or intermediate-1-risk (n = 83) MF. The majority of patients were male (low risk, 60%; intermediate-1 risk, 69%). Most patients (92% and 77%) were still receiving ruxolitinib at the medical record abstraction date (median observation/exposure time, 8 months). The proportion of patients with moderate or severe palpable splenomegaly (≥10 cm) decreased from diagnosis (56%) to best response (12%). Fatigue was reported in 47% of patients and was the most common constitutional symptom. For most symptoms in both risk groups, shifts in the distribution of severity from more to less severe from diagnosis to best response were observed. Both patients with low-risk and intermediate-1-risk MF experienced a substantial decrease in spleen size with ruxolitinib treatment in real-world settings. For most symptoms examined, there were distinct improvements in the distribution of severity during ruxolitinib treatment. These findings suggest that patients with lower-risk MF may benefit clinically from ruxolitinib treatment.

| S-EPMC4655278 | biostudies-literature

Cytopenic overt primary myelofibrosis at presentation: Analysis of outcomes in the prospective, real-world ERNEST-2 registry.

Project description: Not available

| S-EPMC11783225 | biostudies-literature

Real-life ruxolitinib experience in intermediate-risk myelofibrosis.

Project description:BackgroundIn this retrospective cohort of patients with primary, post-polycythemia vera, or post-essential thrombocythemia myelofibrosis, 57 patients with MF who received ruxolitinib for MF-related symptoms or symptomatic splenomegaly were evaluated.MethodsThe median age of the patients in this cohort was approximately 58 years. Of these, there were 33 patients (57.9%) in INT-1, 23 patients (40.4%) in INT-2, and 1 patient (1.8%) at high risk. Overall, spleen size reduction of at least 35% (spleen response) was achieved in 56.6% and 63.3% of all cohort and INT-1 risk at any time, respectively.ResultsSymptom response and clinical improvement were observed in 21.7% and 60.7% of patients, respectively. Anemia and thrombocytopenia were prevalent, but manageable. About 73.7% of patients continued treatment during a median follow-up of 22 months. Two-year OS probability was approximately 84.5% (95% CI, 63.1‒94.0%) and 62.3% (95% CI, 37.5‒79.6%) for the intermediate-1 and -2 risk groups, respectively.ConclusionReal-life experience in a community-based hospital confirms the efficacy and safety profile of ruxolitinib in intermediate-risk myelofibrosis. Treatment discontinuation rates were lower than those in clinical trials.

| S-EPMC8721444 | biostudies-literature

Dosing and clinical outcomes of ruxolitinib in patients with myelofibrosis in a real-world setting: Interim results of the Italian observational study (ROMEI).

Project description:BackgroundMyelofibrosis (MF) significantly impacts patients' overall survival (OS) and quality of life (QOL). This prospective study analyzed ruxolitinib dosing patterns and associated clinical outcomes in patients with MF over 12 months.MethodsROMEI, a multicenter, observational, ongoing study, enrolled 508 adult patients with MF treated with ruxolitinib. For the current interim analysis, eligible patients with baseline platelet values were categorized into two groups based on ruxolitinib starting dosage: as expected (AsEx, n = 174) and lower than expected (LtEx, n = 132); ruxolitinib dose changes, interruptions and time to permanent discontinuation were analyzed, along with symptoms response, health-related QOL scores, spleen response, OS, and safety.ResultsForty-three percent of patients started at a lower-than-expected dose. Both groups showed reduction in average daily ruxolitinib doses over 12 months. Symptoms response rate was similar in both groups at week 48 (40.8% AsEx vs 40.9% LtEx). The AsEx group demonstrated higher spleen response rates at both 24 weeks (50.0% vs 30.2%) and 48 weeks (57.7% vs 45.8%) with a shorter median time to first response (3.3 vs 11.1 months, p = .019) when compared to the LtEx group. Both groups showed upward trends in health-related QOL values. Estimated median OS was not reached for the AsEx group versus 4.7 years in the LtEx group (p = .014). Adverse events were reported in 87.4% and 84.9% of patients in the AsEx and LtEx groups, respectively.ConclusionsThe ROMEI study demonstrated the importance of optimal ruxolitinib dosage in patients with MF for maximum effectiveness and improved OS, with manageable safety.

| S-EPMC11925231 | biostudies-literature

Impact of ruxolitinib on myelofibrosis patients post allogeneic stem cell transplant-a pilot study.

Project description: Not available

| S-EPMC6706301 | biostudies-literature

Impact of calreticulin mutations on treatment and survival outcomes in myelofibrosis during ruxolitinib therapy.

Project description:Calreticulin (CALR) mutations are detected in around 20% of patients with primary and post-essential thrombocythemia myelofibrosis (MF). Regardless of driver mutations, patients with splenomegaly and symptoms are generally treated with JAK2-inhibitors, most commonly ruxolitinib. Recently, new therapies specifically targeting the CALR mutant clone have entered clinical investigation. To collect information on efficacy and safety of ruxolitinib in CALR-mutated patients, we report a sub-analysis of the "RUX-MF" (NCT06516406) study, comprising 135 CALR-mutated and 786 JAK2-mutated ruxolitinib-treated patients. Compared to JAK2-mutated patients, CALR-mutated patients started ruxolitinib with a more severe disease (higher peripheral blast counts, lower hemoglobin levels and worse marrow fibrosis) and after a longer median time from diagnosis (2.6 versus 0.7 years, p < 0.001). At 6 months, spleen responses were numerically inferior in CALR-mutated patients, who also had significantly lower rates of symptom responses (56.1% versus 66.7%, p = 0.04).

| S-EPMC11868333 | biostudies-literature

The impact of anemia on overall survival in patients with myelofibrosis treated with ruxolitinib in the COMFORT studies.

Project description: Not available

| S-EPMC5479619 | biostudies-literature