Ruxolitinib (RUX) retreatment in patients (Pts) with myelofibrosis (MF): Real-world evidence on pt characteristics and outcomes.

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. e19535-e19535 ◽  
Author(s):  
Naveen Pemmaraju ◽  
Jingbo Yu ◽  
Shreekant Parasuraman ◽  
Dilan Paranagama ◽  
Jonathan Kish ◽  
...  
Keyword(s):  
Case Reports ◽  
Spleen Size ◽  
Jak Inhibitors ◽  
Clinical Practices ◽  
Community Based ◽  
Future Studies ◽  
Jak2 Inhibitor ◽  
Loss Of Response ◽  
Integrated Research ◽  
Real World Evidence

e19535 Background: RUX is a JAK1/JAK2 inhibitor FDA-approved for treatment (tx) of int/high risk MF. In the COMFORT studies, RUX reduced spleen volume in pts with MF (primary endpoint), with a median time to response of 3 mo. Case reports and clinical studies have shown some pts’ symptoms and/or splenomegaly improve upon RUX reinitiation after interruption. In the era of novel JAK inhibitors (JAKi), dose optimization and identifying indicators for tx changes remain major challenges. This study describes tx patterns and clinical outcomes of pts with MF with RUX interruption and retreatment in community-based clinical practices. Methods: Two independent patient care data sources were queried (not directly compared): (1) Cardinal Health Oncology Provider Extended Network (OPEN), (2) HealthCore Integrated Research Environment (HIRE); retrospective review of medical charts was conducted. Rigorous entry criteria for this analysis included: age ≥18 y; primary MF (PMF), post-polycythemia vera (PV) MF, or post-essential thrombocythemia (ET) MF diagnosis between 1/1/2012–12/31/2016 (OPEN) or 1/2013–11/2017 (HIRE); use of RUX for MF; and documented physician-directed RUX interruption. MF-related symptoms, splenomegaly, and tx dose and patterns were analyzed. Results: 26 pts met entry criteria (Table). Pre-interruption median (IQR) RUX tx duration was 123 (57–391, OPEN) and 110 (37–148, HIRE) days; 50% had tx interruption within 3 mo. Most interruptions were for adverse events (AEs; 50% and 71%, respectively), followed by (in OPEN) alternative tx (17%), disease progression (8%), no response (8%), or loss of response (8%). After restarting RUX, median (IQR) retreatment duration was 196 (54–553) and 166 (108–262) days, respectively. Symptoms improved in 45% and 43% of evaluable pts, respectively, and spleen size improved in 40% and 33%. Conclusions: Consistent with previous reports, MF symptoms and spleen size improved with RUX retreatment in some pts. While RUX was discontinued for various reasons, one reason for clinical improvements upon reinitiation may be that tx was discontinued before deriving full JAKi benefit. Future studies are warranted investigating JAKi tx sequencing and reinitiation. [Table: see text]

Ruxolitinib Re-Treatment in Patients with Myelofibrosis: Real-World Evidence on Patient Characteristics and Outcomes

2022 ◽  
pp. 1-5
Author(s):  
Aaron T. Gerds ◽  
Jingbo Yu ◽  
Robyn M. Scherber ◽  
Dilan Paranagama ◽  
Jonathan K. Kish ◽  
...  
Keyword(s):  
Treatment Duration ◽  
Treatment Options ◽  
Patient Characteristics ◽  
Spleen Size ◽  
Spleen Volume ◽  
Phase 3 ◽  
Secondary Use ◽  
Integrated Research ◽  
Real World Evidence ◽  
Dose Modifications

Ruxolitinib is an FDA-approved treatment of intermediate- and high-risk myelofibrosis. In the phase 3 COMFORT studies, ruxolitinib reduced spleen volume in patients with myelofibrosis, with a median time to response of 3 months. However, nearly 20% of patients discontinued by month 4 with few treatment options available following discontinuation of ruxolitinib treatment. In this study, 2 independent patient care data sources were queried (Cardinal Health Oncology Provider Extended Network [OPEN] and HealthCore Integrated Research Environment [HIRE®]), and a retrospective review of medical charts was conducted. Patients aged ≥18 years with a diagnosis of myelofibrosis (primary or secondary), use of ruxolitinib for myelofibrosis, and documented physician-directed ruxolitinib interruption were included. Among 26 included patients, pre-interruption median (interquartile range [IQR]) ruxolitinib treatment duration was 123 (57–391, OPEN) and 110 (37–148, HIRE) days. Half the patients interrupted treatment within 3 months, commonly for adverse events (42% and 71%, respectively). After restarting ruxolitinib, median (IQR) re-treatment duration was 196 (54–553) and 166 (108–262) days, respectively. Consistent with previous reports, symptoms and spleen size improved in (OPEN/HIRE) 45%/43% and 40%/33% of evaluable patients, respectively. Further studies investigating the management of dose modifications and interruptions are needed to optimize benefit from ruxolitinib therapy.

scholarly journals Efficacy and safety of urate-lowering therapy in people with kidney impairment: a GCAN-initiated literature review

2021 ◽  
Author(s):  
Hamish Farquhar ◽  
Ana B Vargas-Santos ◽  
Huai Leng Pisaniello ◽  
Mark Fisher ◽  
Catherine Hill ◽  
...  
Keyword(s):  
Renal Function ◽  
Renal Impairment ◽  
Case Reports ◽  
Serum Urate ◽  
Cochrane Library ◽  
Future Studies ◽  
Kidney Impairment ◽  
The Cochrane Library ◽  
Study Designs ◽  
Different Levels

Abstract Objectives To evaluate the efficacy, defined as achieving target serum urate <6.0 mg/dl, and safety of urate-lowering therapies (ULT) for people with gout and CKD stages 3–5. Methods PubMed, The Cochrane Library, and EMBASE, were searched from 1 January 1959 to 31 January 2018 for studies that enrolled people with gout, who had an estimated glomerular filtration rate (eGFR) or creatinine clearance (CrCl) of < 60 mL/min, and exposure to allopurinol, febuxostat, probenecid, benzbromarone, lesinurad or pegloticase. All study designs other than case reports were included, except for people on dialysis, for which we did include case reports. Results There were 36 reports with an analysis of efficacy and/or safety based upon renal function – allopurinol (n = 12), febuxostat (n = 10), probenecid (n = 3), benzbromarone (n = 5), lesinurad (n = 5), and pegloticase (n = 1). There were 108 reports that involved people with gout and renal impairment but did not contain any analysis on efficacy and/or safety based upon renal function – allopurinol (n = 84), febuxostat (n = 14), benzbromarone (n = 1), lesinurad (n = 3), and pegloticase (n = 6). Most studies excluded people with more severe degrees of renal impairment (eGFR or CrCl of < 30mL/min). For allopurinol in particular, there was significant variability in the dose of drug used, and efficacy in terms of urate lowering, across all levels of renal impairment. Conclusion There is a lack of evidence regarding efficacy and/or safety of currently used ULT according to different levels of renal function. Future studies should include patients with CKD and should report study outcomes stratified by renal function.

JAK inhibition in the myeloproliferative neoplasms: lessons learned from the bench and bedside

Hematology ◽  
2013 ◽  
Vol 2013 (1) ◽  
pp. 529-537 ◽  
Author(s):  
Jason Gotlib
Keyword(s):  
Myeloproliferative Neoplasms ◽  
Symptom Burden ◽  
Jak2 V617f ◽  
Lessons Learned ◽  
Jak Inhibitors ◽  
Jak2 Inhibitor ◽  
Sequencing Technologies ◽  
Cell Growth And Differentiation ◽  
Scientific Context ◽  
Generation Sequencing

AbstractThe discovery of the JAK2 V617F mutation in the classic BCR-ABL1–negative myeloproliferative neoplasms in 2005 catalyzed a burst of research efforts that have culminated in substantial dividends for patients. Beyond JAK2 V617F, a more detailed picture of the pathobiologic basis for activated JAK-STAT signaling has emerged. In some patients with myelofibrosis (MF), next-generation sequencing technologies have revealed a complex clonal architecture affecting both genetic and epigenetic regulators of cell growth and differentiation. Although these bench-top findings have informed the clinical development of JAK inhibitors in MF, they have also provided scientific context for some of their limitations. The JAK1/JAK2 inhibitor ruxolitinib is approved for treatment of MF in North America and Europe and other lead JAK inhibitors discussed herein (fedratinib [SAR302503], momelotinib [CYT387], and pacritinib [SB1518]), have entered advanced phases of trial investigation. Uniformly, these agents share the ability to reduce spleen size and symptom burden. A major challenge for practitioners is how to optimize dosing of these agents to secure clinically relevant and durable benefits while minimizing myelosuppression. Suboptimal responses have spurred a “return to the bench” to characterize the basis for disease persistence and to inform new avenues of drug therapy.

scholarly journals Cataract among elderly in Sri Lanka

2019 ◽  
Author(s):  
A.A. Nilanga Nishad ◽  
S.A. Hewage ◽  
K. Arulmoly ◽  
M.S. Amaratunge ◽  
J de Silva ◽  
...  
Keyword(s):  
Sri Lanka ◽  
Screening Programme ◽  
National Level ◽  
Age Groups ◽  
Cross Sectional Study ◽  
Community Based ◽  
Cross Sectional ◽  
Future Studies ◽  
Factors Associated ◽  
Younger Age

AbstractOut of 39 billion people who are blind around the world, 20 billion (51.3%) is due to cataract, which is preventable. This study intended to assess the prevalence and factors associated with cataract among elderly in a divisional secretariat area in Sri Lanka. This community based cross sectional study assessed randomly selected470 adults over 60 years of age. Diagnosis of cataract was made by a slit lamp examination by medical officers, and classified according to Oxford Lens Opacity Classification system (LOCS III). Majority was between 60-69 age groups and 71% was females. The prevalence of cataract was estimated to be 80.6% including operated eye and 73.6% excluding the operated eye, with a female preponderance in lower age categories. Commonest type of cataract was the nuclear type (n=422; 44.9%), with a majority in grade 2 (218; 23.2%). The prevalence of cataract surgery in the diseased population was as low as 7%. Cataract leading to blindness is very prevalent among adults over 60 years of age in the studied area. Females tend to develop the disease at an early age than males. These findings warrant screening programme for elderly at community level, targeting females at a younger age than males. Future studies are recommended to assess the coverage and barriers for cataract surgeries at national level, which would be immensely useful in planning and improving health services.

The Association between Self-reported Osteoporosis and Chinese Medicine-Constitution Questionnaire – A Cross-Sectional Taiwan Biobank Study

2020 ◽  
Author(s):  
Hsien-Hui Yang ◽  
Chih-Sheng Chen ◽  
Hsin-Yi Lo ◽  
Chien-Yi Ho ◽  
Chia-Hung Kao ◽  
...  
Keyword(s):  
Chinese Medicine ◽  
Residual Effect ◽  
Cross Sectional Study ◽  
P Value ◽  
Community Based ◽  
Cross Sectional ◽  
Drinking Habits ◽  
False Discovery ◽  
Real World Evidence ◽  
Constitutional Medicine

Abstract Background: Constitutional medicine was as an example of earlier medicine evidence of Chinese Medicine (CM). CM-Constitutional Questionnaire (CM-CQ) commonly considered as the observed various phenotypes as phenome. However, the comprehensive associations between self-reported disease outcomes and questionnaires of CM-CQ remained uncertain. Methods: Taiwan Biobank has begun the collection of these cancer-free volunteers, aged 30-70 with these questionnaires, self-reported disease history, clinical examinations, and genetic information from 2012 as baseline enrollment. This community-, cross-sectional study was conducted by part of Taiwan Biobank and compared the associations among CM-CQ, which reflect these constitutional variables as individual markers.Results: The present study conducted by using 1,998 volunteers (2 withdraw) from Taiwan Biobank. Which separately assessed the associations among 32 diseases and 44 items of CM-CQ questions using the binomial logistic regression model. There were 6 CM-CQ questions with a significant association of self-reported osteoporosis in all CM-CQ. Interestingly, we found that these 6 CM-CQ questions shown a significant association with osteoporosis, even which adjusted with false discovery rate (adjusted p <0.05). The Q1, Q22, and Q37 demonstrated with considerably adjusted p-value and the other CM-CQ, which involved in Q14, Q16, and Q21 shown borderline relation to self-reported osteoporosis, which was existed less residual effect with smoking and drinking habits. Conclusion: This study generated real-world evidence of national biobank for clarified associations between clinical symptom and self-reported diseases. The exploration of self-reported disease-related CM-CQ for further companion diagnostic indicators via comprehensive community-based Taiwan Biobank study should be a possibility.

scholarly journals Treatment of Chronic Myelomonocytic Leukemia with 5-Azacytidine: Case Reports

2012 ◽  
Vol 2012 ◽  
pp. 1-4 ◽  
Author(s):  
Peter Rohon ◽  
Jana Vondrakova ◽  
Anna Jonasova ◽  
Milena Holzerova ◽  
Marie Jarosova ◽  
...  
Keyword(s):  
Myeloid Leukemia ◽  
Case Reports ◽  
Quality Adjusted Life Year ◽  
Chronic Myelomonocytic Leukemia ◽  
Epigenetic Therapy ◽  
Event Free Survival ◽  
Free Survival ◽  
Future Studies ◽  
Myelomonocytic Leukemia ◽  
Quality Adjusted Life

Epigenetic therapy with hypomethylating agent (5-azacytidine; AZA) is common in the management of specific subtypes of myelodysplastic syndrome (MDS), but there are only few studies in chronic myelomonocytic leukemia (CMML) patients. In this paper our experience with 3 CMML patients treated with AZA is described. In one patient transfusion independency was observed after 4 treatment cycles; in one case a partial response was recorded, but a progression to acute myeloid leukemia (AML) after 13 AZA cycles has appeared. In one patient, AZA in reduced dosage was administered as a bridging treatment before allogeneic stem cell transplantation (ASCT), but in the control bone marrow aspirate (before ASCT) a progression to AML was recorded. Future studies are mandatory for evaluation of new molecular and clinical features which could predict the efficiency of hypomethylating agents in CMML therapy with respect to overall survival, event-free survival, quality-adjusted life year, and pharmacoeconomy.

scholarly journals Lyophilizing thrombin powder-based treatment for hemostasis during coil embolization of ruptured cerebral aneurysm: Two case reports

2019 ◽  
Vol 25 (4) ◽  
pp. 454-459
Author(s):  
Changchun Jiang ◽  
Wei Wang ◽  
Baojun Wang ◽  
Yuechun Li ◽  
Guorong Liu ◽  
...  
Keyword(s):  
Cerebral Aneurysm ◽  
Coil Embolization ◽  
Case Reports ◽  
Balloon Catheter ◽  
Treatment Strategies ◽  
Cerebral Aneurysms ◽  
Interventional Therapy ◽  
Parent Artery ◽  
Clinical Practices ◽  
Detachable Coils

Background Rupture of cerebral aneurysm is an inevitable complication during embolization, followed by subsequent acute subarachnoid hemorrhage or intracranial hematoma, and results in the aggravation of a patient’s condition. In particular, for patients who have had a ruptured aneurysm, urgent treatment strategies are required during operation. The most common hemostatic methods seen in clinical practices are as follows: after lowering the blood pressure, we continue to embolize the aneurysms with detachable coils as soon as possible or inject with Glubran/Onyx embolization liquids, as well as use a balloon catheter to temporarily block the blood supply. If the conditions are permissible, a balloon guiding catheter may even be used to restrict the proximal blood flow. At times, due to limitations of these methods, neurosurgeons are requested to perform craniotomy to treat the hemostasis. However, the delayed transition often leads to rapid deterioration of the patient’s condition and even death due to cerebral hernia. Case description We herein presented two cases of ruptured cerebral aneurysms to provide an alternative method for hemostasis and to save the lives of patients as much as possible. In an extremely urgent situation (conventional treatment is ineffective), we successfully saved the patient’s life by injecting lyophilizing thrombin powder (LTP) solution into the aneurysmal sac and the parent artery through a microcatheter. Conclusions To our knowledge, this is the first report of successful hemostasis during coil embolization of ruptured cerebral aneurysm with LTP. Further prospective studies are needed to confirm the safety and efficacy of LTP in cerebrovascular interventional therapy.

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