Validation and molecular integration of the RR6 model to predict survival after 6 months of therapy with ruxolitinib (original) (raw)
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Ruxolitinib Clinical and Microbiological Implications and Possible Association with B Cell Lymphoma
Cukurova Anestezi ve Cerrahi Bilimler Dergisi
Introduction: Ruxolitinib is a Janus kinase (JAK)1/JAK2 inhibitor for the treatment with primary myelofibrosis (PMF), postpolycythemia MF (PPVMF), and post-essential thrombocythemia MF (PETMF) for disease-related splenomegaly or symptoms in adult patients. Ruxolitinib is effective treatment choice for myelofibrosis. But ruxolitinib has some adverse event, hematologic and non-hematologic. In this study, we wanted to present the results of our patients using ruxolitinib. Materials and Methods: Total 40 patient's data were retrospectively analyzed. Categorical and continuous data were expressed as ratio (%) and median (range). Overall survival (OS) is taken as endpoints of this study. Results: The total number of patients was 40. 4 patients received ruxolitinib for chronic graft versus host disease (cGVHD) after allogeneic stem cell transplantation. The total number of patients who analyzed was 28. The median age of patients was 54 years (35-78). Median ruxolitinib treatment duration was 383 days (37-1596 days). After ruxolitinib, median platelet, hemoglobin, neutrophil nadir durations were 46 days (0-546), 40 days (14-218days) and 112 days (16-546days), respectively. The median nadir hemoglobin and platelet level were 8.3 g/dl (5 g/dl-15 g/dl) and 147.5×10 3 /µl (29×10 3 /µl-589×10 3 /µl), respectively. The median follows up was 1291 days (40-8053 days). The 5-year OS rate was 60.6% and 90% in hemoglobin and platelet recovery time <100days and ≥100 days (p=0.9). 7 patients were died, one of them had opportunistic fungal infection. Conclusion: In conclusion, although ruxolitinib has been shown to improve survival in myelofibrosis in the long term, survival may be short due to side effects.
A prognostic model to predict survival after 6 months of ruxolitinib in patients with myelofibrosis
Blood Advances, 2022
Ruxolitinib (RUX) is extensively used in myelofibrosis (MF). Despite its early efficacy, most patients lose response over time and, after discontinuation, have a worse overall survival (OS). Currently, response criteria able to predict OS in RUX-treated patients are lacking, leading to uncertainty regarding the switch to second-line treatments. In this study, we investigated predictors of survival collected after 6 months of RUX in 209 MF patients participating in the real-world ambispective observational RUXOREL-MF study (NCT03959371). Multivariable analysis identified the following risk factors: (1) RUX dose <20 mg twice daily at baseline, months 3 and 6 (hazard ratio [HR], 1.79; 95% confidence interval [CI], 1.07-3.00; P = .03), (2) palpable spleen length reduction from baseline ≤30% at months 3 and 6 (HR, 2.26; 95% CI, 1.40-3.65; P = .0009), (3) red blood cell (RBC) transfusion need at months 3 and/or 6 (HR, 1.66; 95% CI, 0.95-2.88; P = .07), and (4) RBC transfusion need at a...
British Journal of Haematology, 2013
Myelofibrosis (MF) patients can present with a wide spectrum of disease characteristics. We analysed the consistency of ruxolitinib efficacy across patient subgroups in the COntrolled MyeloFibrosis Study With ORal JAK Inhibitor Treatment (COMFORT-I,) a double-blind trial, where patients with intermediate-2 or high-risk MF were randomized to twice-daily oral ruxolitinib (n = 155) or placebo (n = 154). Subgroups analysed included MF subtype (primary, post-polycythaemia vera, post-essential thrombocythaemia), age (≤65, > 65 years), International Prognostic Scoring System risk group, baseline Eastern Cooperative Oncology Group performance status (0, 1, ≥2), JAK2 V617F mutation (positive, negative), baseline haemoglobin level (≥100, <100 g/l), baseline platelet count (100-200 × 10 9 /l, >200 × 10 9 /l), baseline palpable spleen size (≤10, >10 cm), and baseline quartile of spleen volume and Total Symptom Score (TSS; Q1 = lowest, Q4 = highest). Mean percentage change from baseline to week 24 in spleen volume and TSS were calculated for ruxolitinib and placebo in each subgroup. Overall survival was estimated by Kaplan-Meier method according to original randomization group. In ruxolitinibtreated patients, reductions in spleen volume and TSS and evidence of improved survival relative to placebo across subgroups were consistent with those seen in the COMFORT-I population, confirming that ruxolitinib is an effective therapy for the spectrum of MF patients studied in COMFORT-I.
Journal of Clinical Medicine
The wide use of ruxolitinib, approved for treating primary and secondary myelofibrosis (MF), has revolutionized the landscape of these diseases. This molecule can reduce spleen volume and constitutional symptoms, guaranteeing patients a better quality of life and survival or even a valid bridge to bone marrow transplantation. Despite a rapid response within the first 3 to 6 months of treatment, some patients fail to achieve a significant benefit or lose early response. After ruxolitinib failure, new drugs are available to provide an additional therapeutic option for these patients. However, the correct timing point for deciding on a therapy shift is still an open challenge. Recently, a clinical prognostic score named RR6 (Response to Ruxolitinib after 6 months) was proposed to determine survival after 6 months of treatment with ruxolitinib in patients affected by MF. We applied this model to a cohort of consecutive patients treated at our center to validate the results obtained in t...
Oncotarget, 2017
In patients with Myelofibrosis (MF) treated with ruxolitinib (RUX), the response is unpredictable at therapy start. We retrospectively evaluated the impact of clinical/laboratory factors on responses in 408 patients treated with RUX according to prescribing obligations in 18 Italian Hematology Centers. At 6 months, 114 out of 327 (34.9%) evaluable patients achieved a spleen response. By multivariable Cox proportional hazard regression model, pre-treatment factors negatively correlating with spleen response were: high/intermediate-2 IPSS risk (p=0.024), large splenomegaly (p=0.017), transfusion dependency (p=0.022), platelet count <200x109/l (p=0.028), and a time-interval between MF diagnosis and RUX start >2 years (p=0.048). Also, patients treated with higher (≥10 mg BID) average RUX doses in the first 12 weeks achieved higher response rates (p=0.019). After adjustment for IPSS risk, patients in spleen response at 6 months showed only a trend for better survival compared to no...