The effect of CYP2C9 gene polymorphisms on blood pressure lowering response to losartan in patients with essential hypertension

Purpose: In this study, the possible effects of CYP2C9 polymorphisms on the clinical response to losartan were investigated in a group of hypertensive patients. Materials and Methods: Seventy-four patients, newly diagnosed to have essential hypertension, and were subsequently prescribed losartan by attending physicians, were prospectively recruited for the study. Blood pressure measurements at the initiation of losartan treatment and six weeks after were completed for all participants. Genetic analysis for CYP2C9 polymorphisms was performed in blood samples collected at baseline. CYP2C9 *2 and *3 variant alleles were genotyped, and polymorphic patients' treatment responses were compared with the patients' who were carrying the wild type genotype. Results: Analysis comparing the wild type genotype and CYP2C9*1*2 genotype revealed a trend toward more systolic blood pressure reduction in favor of wild-type genotype. However, there was no statistically significant difference between these two groups considering the change in diastolic blood pressure levels. Regarding the CYP2C9*1*3 genotype, there were no significant differences in systolic or diastolic blood pressure changes. Conclusion: CYP2C9*1*2 polymorphism affects the systolic blood pressure response to losartan in hypertensive patients, while the CYP2C9*1*3 genotype was not shown in associated with systolic or diastolic blood pressure responses.Hacettepe University Scientific Projects Coordination Unit [0801101009]This study was financially supported by Hacettepe University Scientific Projects Coordination Unit (Number: 0801101009)

Efficacy and Safety of Ibrutinib Therapy in Patients with Chronic Lymphocytic Leukemia: Retrospective Analysis of Real-Life Data

Objective: This study aimed to retrospectively evaluate the efficacy, safety, and survival outcome of single-agent ibrutinib therapy in chronic lymphocytic leukemia patients. Materials and Methods: A total of 136 patients (mean age +/- standard deviation: 64.6 +/- 10.3 years, 66.9% males) who had received at least one dose of ibrutinib were included in this retrospective multicenter, noninterventional hospital-registry study conducted at 33 centers across Turkey. Data on patient demographics, baseline characteristics, laboratory findings, and leukemia-cell cytogenetics were retrieved. Treatment response, survival outcome including overall survival (OS) and progression-free survival (PFS), and safety data were analyzed. Results: Overall, 36.7% of patients were categorized as Eastern Cooperative Oncology Group (ECOG) class 2-3, while 44.9% were in Rai stage 4. Fluorescence in situ hybridization revealed the presence of del(17p) in 39.8% of the patients. Patients received a median of 2.0 (range: 0-7) lines of pre-ibrutinib therapy. Median duration of therapy was 8.8 months (range: 0.4-58.0 months). The 1-year PFS and OS rates were 82.2% and 84.6%, respectively, while median PFS time was 30.0 (standard error, 95% confidence interval: 5.1, 20.0-40.0) months and median OS time was 37.9 (3.2, 31.5-44.2) months. Treatment response (complete or partial response), PFS time, and OS time were better with 0-2 lines versus 3-7 lines of prior therapy (p<0.001, p=0.001, and p<0.001, respectively), with ECOG class 0-1 versus class 2-3 (p=0.006, p=0.011, and p=0.001, respectively), and with Rai stage 0-2 versus 3-4 (p=0.002, p=0.001, and p=0.002, respectively). No significant difference was noted in treatment response rates or survival outcome with respect to the presence of comorbidity, bulky disease, or del(17p). While 176 adverse events (AEs) were reported in 74 (54.4%) patients, 46 of those 176 AEs were grade 3-4, including pneumonia (n=12), neutropenia (n=11), anemia (n=5), thrombocytopenia (n=5), and fever (n=5). Conclusion: This real-life analysis confirms the favorable efficacy and safety profile of long-term ibrutinib treatment while emphasizing the potential adverse impacts of poorer ECOG performance status, heavy treatment prior to ibrutinib, and advanced Rai stage on patient compliance, treatment response, and survival outcomes

A Multi-Center Study on the Efficacy of Eltrombopag in Management of Refractory Chronic Immune Thrombocytopenia: A Real-Life Experience

Objective: The aim of the present study was to evaluate the efficacy and safety of eltrombopag, an oral thrombopoietin receptor agonist, in patients with chronic immune thrombocytopenia (ITP)

A Multi-Center Study on the Efficacy of Eltrombopag in Management of Refractory Chronic Immune Thrombocytopenia: A Real-Life Experience

Objective: The aim of the present study was to evaluate the efficacy and safety of eltrombopag, an oral thrombopoietin receptor agonist, in patients with chronic immune thrombocytopenia (ITP). Materials and Methods: A total of 285 chronic ITP patients (187 women, 65.6 \%; 98 men, 34.4\%) followed in 55 centers were enrolled in this retrospective cohort. Response to treatment was assessed according to platelet count (/mm(3)) and defined as complete (platelet count of >100,000/mm(3)), partial (30,000-100,000/mm(3) or doubling of platelet count after treatment), or unresponsive (<30,000/mm(3)). Clinical findings, descriptive features, response to treatment, and side effects were recorded. Correlations between descriptive, clinical, and hematological parameters were analyzed. Results: The median age at diagnosis was 43.9 +/- 20.6 (range: 3-95) years and the duration of follow-up was 18.0 +/- 6.4 (range: 6-28.2) months. Overall response rate was 86.7\% (n=247). Complete and partial responses were observed in 182 (63.8\%) and 65 (22.8\%) patients, respectively. Thirty-eight patients (13.4\%) did not respond to eltrombopag treatment. For patients above 60 years old (n=68), overall response rate was 89.7\% (n=61), and for those above 80 years old (n=12), overall response rate was 83\% (n=10). Considering thrombocyte count before treatment, eltrombopag significantly increased platelet count at the 1st, 2nd, 3rd, 4th, and 8th weeks of treatment. As the time required for partial or complete response increased, response to treatment was significantly reduced. The time to reach the maximum platelet levels after treatment was quite variable (1-202 weeks). Notably, the higher the maximum platelet count after eltrombopag treatment, the more likely that side effects would occur. The most common side effects were headache (21.6\%), weakness (13.7\%), hepatotoxicity (11.8\%), and thrombosis (5.9\%). Conclusion: Results of the current study imply that eltrombopag is an effective therapeutic option even in elderly patients with chronic ITP. However, patients must be closely monitored for response and side effects during treatment. Since both response and side effects may be variable throughout the follow-up period, patients should be evaluated dynamically, especially in terms of thrombotic risk factors