Hb Response Rate Research Articles

The clinical efficacy of combined ESA and Roxadustat treatment for renal anemia in hemodialysis patients with secondary hyperparathyroidism: A case series.

Pharmacological mechanism of Roxadustat in the treatment of renal anemia. To investigate the efficacy and safety of combined Roxadustat and erythropoiesis stimulator (ESA) treatment of renal anemia in hemodialysis patients with secondary hyperparathyroidism. A retrospective analysis was conducted on hemodialysis patients with renal anemia and secondary hyperparathyroidism treated with ESAs alone, who were admitted to our hospital from March 2022 to December 2022. The patients were treated with Roxadustat combined with ESAs for 3 months, during which oral iron supplementation was given, and the changes in Hb levels and laboratory-related indicators before and after the combined treatment were analyzed. The results showed that a total of 13 patients received combination therapy, with a significant increase in Hb compared to ESAs alone (t = -3.955, P = .002). The Hb qualification rate was 38.46%, and the ∆Hb response rate was 76.92%. The parathyroid hormone significantly decreased with a statistically significant difference (Z = -2.062b, P = .039). Hemoglobin (RBC), total iron binding capacity, and serum ferritin (male) were significantly increased compared to ESAs alone. Total cholesterol and low-density lipoprotein were significantly lower than ESAs alone. The differences in the changes in the above indicators were statistically significant (P < .05). There was no statistically significant difference in changes in other laboratory-related indicators (P > .05). No adverse reactions were observed during the combined treatment of 13 patients. The combination of Roxadustat and ESAs can effectively improve renal anemia in hemodialysis patients with secondary hyperparathyroidism, as well as improve indicators of hyperparathyroidism and blood lipid levels with high levels of safety. This combined treatment thus provides a new and safe treatment method for these patients.

#2352 Short-term effect of roxadustat combined with ESA treatment for anemia in patients undergoing hemodialysis with ESA hyporesponsiveness

Abstract Background and Aims The efficacy of roxadustat combined with erythropoiesis-stimulating agent (ESA) on renal anemia in maintenance hemodialysis (MHD) patients is rarely reported, especially for those with ESA hyporesponsiveness. Our study aimed to observe the short-term efficacy of roxadustat combined with ESA for those patients when they were first treated with roxadustat converted from ESA. Method Retrospective data pertaining to MHD patients with ESA hyporesponsiveness from September 2019 to June 2022 were collected. All patients had been on ESA for more than 6 months and were first treated with roxadustat. 19 patients treated with roxadustat combined with ESA and 19 patients treated with roxadustat alone were paired for analysis from 108 patients by propensity score matching. Parameters related to anemia, iron metabolism and adverse events were recorded. Results The haemoglobin (Hb) level was significantly improved in patients treated with roxadustat combined with ESA after 1 month (7.8 ± 1.54 g/dL vs 8.96 ± 1.38 g/dL, p = 0.003), which was not found in patients treated with roxadustat alone (8.2 ± 1.28 g/dL vs 8.35 ± 1.54 g/dL, p = 0.652). Patients treated with roxadustat combined with ESA had a higher Hb response rate (47.4%) than those treated with roxadustat alone (15.8%) during the first month (p = 0.036). In addition, the level of serum iron was increased, and serum ferritin (SF) was decreased in both groups. Conclusion Roxadustat combined with ESA treatment might be more beneficial for improving renal anemia in MHD patients with ESA hyporesponsiveness during the first month of roxadustat therapy replacement.

The Efficacy and Safety of Roxadustat for the Treatment of Posttransplantation Anemia: A Randomized Study

IntroductionRoxadustat, an oral hypoxia-inducible factor prolyl hydroxylase inhibitor, can stimulate erythropoiesis. Our objective was to evaluate the efficacy and safety of roxadustat for the treatment of post-transplantation anemia (PTA). MethodsA total of 150 adult renal transplant recipients who underwent PTA were randomized to either the experimental group or the control group. During the 12-week randomized phase, the experimental group was randomized to oral iron and roxadustat treatment, and the control group was randomized to oral iron treatment only. The randomized phase was followed by a 12-week extended treatment period in which all participants were prescribed roxadustat treatment according to hemoglobin (Hb) levels. All the participants were followed up every 4 weeks. The primary endpoints were the change in Hb levels and response rate throughout the randomized period. ResultsA total of 128 participants completed the randomized treatment period (90 in the experimental group and 38 in the control group). The mean Hb concentration at week 12 was 12.20 g/dL in the experimental group and 11.19 g/dL in the control group. A significantly higher proportion of participants who achieved Hb responses were in the experimental group than in the control group. Differences in serum iron, total iron-binding capacity (TIBC) and transferrin from baseline to week 8-12 were significant between the two groups. The adverse event profiles were comparable between the two groups. ConclusionsRoxadustat increased Hb in adult renal transplant recipients who underwent PTA, with an adverse event profile comparable to that of the control group.

#4927 DARBEPOETIN ALFA ONCE IN 4 WEEKS CORRECTS ANEMIA IN PATIENTS WITH CHRONIC KIDNEY DISEASE NOT ON DIALYSIS

Abstract Background and Aims In anemia management in patients with CKD not on dialysis (CKD ND), darbepoetin alfa (DA), which has shorter half-life but lower cost than continuous erythropoietin receptor activator (C.E.R.A.), is preferred in actual clinical practice in Korea. The current study evaluated the efficacy and safety of DA every 4 weeks (Q4W) compared to C.E.R.A. Q4W administration for in erythropoiesis-stimulating agent (ESA)-naïve patients with CKD ND. Method In this randomized, prospective, noninferiority study, 40 ESA-naïve patients with CKD ND were randomized 1:1 to receive either DA or C.E.R.A. Q4W during a 12-week correction period and 24-week efficacy evaluation period (EEP). Two primary efficacy end points were analysed: 1) the mean difference in the changes in haemoglobin (Hb) levels between baseline and EEP and 2) the Hb response rates defined as the proportion of patients who reached the target Hb level range (10-11 g/dL) during correction period. The non-inferiority margin is pre-defined as: 1) The lower limit of the 95% confidence interval (CI) is &amp;gt;-0.75 g/dL for the mean difference in the changes in Hb levels and 2) &amp;gt;60% for Hb response rates. Safety profiles including changes in blood pressure (BP), laboratory safety parameters, and frequency of all adverse events (AEs) were monitored and analysed during study period. Results The mean difference in the changes in Hb levels between the two groups was [0.375 g/dL; 95% confidence interval (CI), -0.446 to 1.196)] and [-0.070 g/dL; 95% CI, -0.730 to -0.590] in the intent-to-treat (ITT) and per-protocol (PP) population, respectively (Fig. 1). The Hb response rates in correction period were comparable between DA and C.E.R.A. group; [100%; 95% CI, 81.4 to 100] versus [94.1%; 95% CI, 71.3 to 99.8)] and [100%; 95% CI, 79.4 to 100] versus [100%; 95% CI: 88.2 to 100)] in ITT and PP population, respectively (Fig. 2). The mean estimated glomerular filtration rate, systolic and diastolic BP, sodium, and potassium level over time were not different during total study period between two groups (P = 0.264, 0.999, 0.823, 0.941, and 0.978). All of the AEs in each group were reported to be mild to moderate in intensity. Peripheral edema, neck pain, herpes zoster, and dyspnea occurred in DA group (20%) and urinary tract infection, dyspnea, and femur neck fracture occurred in C.E.R.A. group (15%). There were no serious AEs which led to discontinuation of the treatment. All AEs were mild to moderate in severity, and they are probably not associated with the study drugs and were successfully cured. The reasons for discontinuation of the drugs were starting HD or follow-up loss, but not due to the administered study drugs. No subjects received RBC transfusion or iron replacement therapy in both groups. There was no death during the study period. Conclusion These study results suggest that DA Q4W has non-inferiority in anemia correction efficacy and similar safety profiles compared to C.E.R.A. Q4W in ESA-naïve patients with CKD ND.

Effect of Roxadustat versus erythropoietin (EPO) for treating anemia in patients with diabetic kidney disease: a retrospective cohort study

Renal anemia of diabetic kidney disease (DKD) shows higher incidence rate, earlier onset and higher severity than other chronic kidney disease (CKD). Roxadustat, an oral hypoxia-inducible factor-prolyl hydroxylase inhibitor, improves CKD anemia. This retrospective cohort study evaluates if Roxadustat could effectively treat DKD anemia. DKD anemia patients treated with either Roxadustat or erythropoietin (EPO) for 3 months in two hospitals were enrolled. EPO group were matched 1:1 to Roxadustat group based on age, gender and baseline Hb. Baseline data include age, sex, dialysis, height, weight, hemoglobin (Hb), hematocrit (Hct), serum albumin (ALB), serum creatinine (Scr), eGFR, C-reactive protein (CRP), and intact parathyroid hormone (iPTH). Primary and secondary outcomes were change of Hb (ΔHb) and Hct (ΔHct), Hb response rate and Hb qualified rate. Sensitivity analyses were performed and the effect size were calculated. No significant differences were observed in body mass index (BMI), Scr, eGFR, Hct, CRP, and dialysis between the 2 groups (61 subjects each). ALB, iPTH, and DKD stage differed between the 2 groups. After 3-month treatment, Roxadustat significantly increased patients' Hb and Hct. Although ΔHb and ΔHct of the Roxadustat group was higher than those of EPO group, difference in the least-square mean changes (95% CI) were 4.9 (-2.4, 12.1) and 1.2 (-1.1, 3.4), while Cohen's d were 0.18 and 0.14, suggesting that Roxadustat's ability to increase Hb within 3-month was similar to EPO. 78.7% and 54.1% of the patients responded to anti-anemia therapy in the Roxadustat and EPO group, respectively. Logistic regression analysis showed the Hb response rate of Roxadustat was 3.30 (1.20, 9.94) times higher than that of EPO. Subgroup analysis suggested that Roxadustat might have better efficacy in treating patients in the advanced stage, with high CRP and iPTH, and low ALB levels. In DKD patients, Roxadustat improves renal anemia. Effect of Roxadustat is similar to that of EPO.

MO796: Short-Term Effect of Roxadustat Combined With Erythropoiesis Stimulating Agents (ESAS) Treatment for Anemia in Patients Undergoing Hemodialysis With ESA Resistance

Abstract BACKGROUND AND AIMS Renal anemia is a common complication of chronic kidney disease (CKD) that can decrease the quality of life of patients, especially for patients with maintenance hemodialysis (MHD). The current standard treatment for renal anemia consists of iron plus erythropoiesis-stimulating agents (ESAs). However, high-dose ESA supplementation may cause an increase in blood pressure and induce cardiovascular events and death [1]. Roxadustat (FG-4592) is a new small-molecule oral medication for the treatment of renal anemia that may improve anemia by increasing endogenous erythropoiesis, transferrin receptor expression, and iron absorption [2]. Currently, the use of roxadustat in the treatment of renal anemia is still being explored. Our study aimed to observe the short-term efficacy of roxadustat combined with ESAs on renal anemia in MHD patients with ESA resistance. METHOD This retrospective study included patients with renal anemia using roxadustat for the first time at West China Hospital of Sichuan University from September 2019 to March 2021. Study inclusion criteria: (1) MHD for &amp;gt;3 months (thrice weekly), (2) basal Hb ≤ 100 g/L and (3) ESAs therapy for &amp;gt;2 months, and the first time use of rosadustat for at least 1 month. We excluded those without hemoglobin data and those with a history of blood transfusion within the first month. Patients treated with roxadustat combined with ESAs were as an observation group, and those treated with roxadustat alone were included as a control group. RESULTS A total of 31 MHD patients were included, the baseline data was shown in Table 1. A total of 15 patients were treated with roxadustat combined with ESAs, and 16 patients were treated with roxadustat alone. In the first month, the mean hemoglobin level was significantly increased in the combined group (1.89 ± 1.45 g/dL) but decreased in the alone group (–0.25 ± 1.32 g/dL). According to an analysis of covariance (ANCOVA), after adjusting for basal hemoglobin levels, the combination therapy improved the hemoglobin level better than therapy alone (F = 6.329, P = .018). We defined the Hb response as: hemoglobin change from baseline ≥ 1 g/dL for patients with basal Hb &amp;gt;8.0 g/dL or ≥ 2.0 g/dL for patients with basal Hb ≤8.0 g/dL. Among the 15 patients treated with roxadustat combined with ESAs, 14 patients showed an increase in hemoglobin within the first month and 8 patients get the Hb response, with the Hb response rate of 53.3%. For the 16 patients treated with roxadustat alone, 7 patients showed an increase in hemoglobin, only 2 patients get the Hb response, with the Hb response rate 12.5%. Patients treated with roxadustat combined with ESAs had a higher Hb response rate (P = .023) than those with roxadustat alone within the first month. CONCLUSION Roxadustat combined with ESAs treatment might be more beneficial to improve renal anemia in MHD patients with ESA resistance during the first month of roxadustat therapy replacement.

Efficacy and Safety of Vadadustat for Anemia in Patients With Chronic Kidney Disease: A Systematic Review and Meta-Analysis.

Background: Vadadustat is a novel drug for treating anemia patients with chronic kidney disease (CKD), but its effect and safety remain uncertain. This study aimed to summarize the evidence for vadadustat in the treatment of CKD patients with anemia. Methods: PubMed, Ovid Medline, Embase, Cochrane CENTRAL, Wanfang Data, China National Knowledge Infrastructure and an international trial register were searched from their inception to June 2021 for randomized controlled trials (RCTs) comparing the efficacy and safety of vadadustat to those of placebo or erythropoiesis-stimulating agents (ESAs) in treating anemia in CKD patients. Data were pooled in a meta-analysis, with results expressed as the mean difference for continuous outcomes and relative risk for categorical outcomes with 95% confidence intervals (95% CIs). The certainty of evidence was rated according to Cochrane methods and the GRADE approach. Results: Ten RCTs comparing vadadustat with placebo (4 RCTs) or darbepoetin alfa (6 RCTs) were included (n = 8,438 participants). Compared with placebo, vadadustat increased the hemoglobin (Hb) response rate (risk ratio 5.27; 95% CI: 2.69 to 10.31; p < 0.001; high certainty of evidence) and Hb level from baseline (∆Hb) (mean difference (MD) 1.28; 95% CI: 0.83 to 1.73; p < 0.001; low certainty of evidence). Compared with placebo or darbepoetin alfa, vadadustat decreased hepcidin (MD -36.62; 95% CI: −54.95 to −18.30; p < 0.001) and ferritin (MD −56.24; 95% CI: −77.37 to −35.11; p < 0.001) levels and increased iron-binding capacity (MD 24.38; 95% CI: 13.69 to 35.07; p < 0.001), with a low to moderate certainty of evidence. Moderate to high certainty evidence suggested that compared with placebo or darbepoetin alfa, vadadustat significantly increased the risk of nausea and diarrhea but did not significantly increase the risk of serious adverse events, especially all-cause mortality, cardiac events and nonfatal stroke. Conclusion: Vadadustat may safely improve Hb levels and promote iron utilization in CKD patients with anemia without increasing the incidence of serious adverse events.

Intravenous Iron Supplementation Alone for Treatment of Anemia in Cancer Patients

Introduction: Anemia is a common issue in cancer patients and multifactorial pathogenesis is involved. Defining the cause of anemia is not easy, and patients usually left untreated with sub-optimal diagnoses of cause. Recently, evidence is emerging to suggest a role for intravenous (IV) iron alone in anemia with cancer patients. Herein, we evaluated the efficacy of IV iron for improvement of anemia in cancer patients.Methods: Eligible patients were as followed; 1) adult patients aged 18 or more who were diagnosed with solid cancer or lymphoma, 2) who were treated with anticancer therapy within 2 months of enrollment, 3) whose hemoglobin (Hb) level of 8.0-10.5g/dL or who experienced a drop of Hb by 2 g/dL or more from baseline. Patients who meet the following criteria were excluded; 1) who received iron replacement or erythropoietin stimulating agent within 4 weeks or enrollment, 2) who has ongoing bleeding, 3) whose disease with bone marrow involvement , 4) ferritin > 800ng/ml and TSAT (transferrin saturation) ≥ 50%. At first visit after enrollment (visit 0), ferinject® (ferric carboxymaltose) 1000mg was administered intravenously. Thereafter, hemoglobin (Hb) response defined by increase of Hb ≥ 1.0g/dL or Hb correction ≥ 11.0g/dL (only if baseline Hb was 8.0-10.5g/dL) was assessed at visit 1, visit 2 and visit 3. The interval between each visit should be at least 2 weeks apart, but should not be exceeded 4 weeks.Results: Between Oct 2010 and Jan 2017, a total of 100 patients were enrolled. Of these 100 patients, 89 patients who had followed at least once were analyzed in this study. The median age was 59 years (range, 24-82). Lung cancer was the most common (n=25, 28.1%) followed by breast cancer (n=23, 25.8%), gastrointestinal cancer (n=18, 20.2%), lymphoma (n=15, 16.9%) and other types of solid cancer (n=8, 9.0%). Almost patients received cytotoxic chemotherapy alone (n=49, 55.1%), and the rest received concurrent chemo-radiotherapy (n=4, 4.5%), target agent (n=4, 4.5%) and target agent plus radiotherapy (n=1, 1.1%). Of 89 patients, 61 patients completed 3 times of follow-up (68.5%) after IV iron treatment, whereas 21 (23.6%) and 7 patients (7.9%) completed 1 and 2 times of follow-up only. Overall, Hb response after administration of ferinject® was noticed in 57 out of 89 patients enrolled (64.0%). Regarding the timing of Hb response by follow up visit, 33, 18 and 6 patients showed Hb response at visit 1 (57.9%), visit 2 (31.6%) and visit 3 (10.5%), respectively. When excluding 16 patients (18.0%) with absolute iron deficiency anemia (IDA) defined by ferritin <30ng/mL or TSAT <20%, Hb response rate in remaining 73 patients was 57.5%. Of these 73 patients, there were 53 patients with functional IDA defined by ferritin 30-500ng/mL and TSAT <50%. No significant difference was observed in Hb response rate between patients with and without functional IDA (62.3% vs 45.0.%, p=0.183). There were 10 patients enrolled whose ferritin > 800ng/mL or TSAT ≥ 50%, in which 5 of 10 patients showed Hb response (50.0%).Conclusion: IV iron supplementation alone showed promising result in improving anemia in cancer patients. This is only a preliminary report and analysis of biochemical parameters for selecting patients who may benefit from IV iron treatment is in progress. DisclosuresNo relevant conflicts of interest to declare.

Roxadustat for the treatment of anemia in patients with chronic kidney diseases: a meta-analysis.

Background: Anemia is a common complication of chronic kidney disease (CKD). Treating renal anemia with erythropoiesis-stimulating agents (ESAs) or erythropoietin analogs is effective but has side effects. Therefore, we performed a meta-analysis to assess the efficacy and safety of roxadustat in treating CKD-induced anemia.Methods: We searched publications online and conducted a meta-analysis and calculated relative risks with 95% confidence intervals (CIs) for dichotomous data and mean differences (MD) with 95% CIs for continuous data.Results: Of 110 articles, nine were included that contained 12 data sets and 11 randomized control trials on roxadustat. In the non-dialysis-dependent (NDD) high-dose/low-dose subgroups, the change in hemoglobin (Hb) levels was significantly higher in the roxadustat group than in the placebo group (P<0.0001, P=0.001, respectively). The Hb response rate of the roxadustat is higher in the NDD subgroup than in the placebo group (P<0.00001, MD=6.92, 95% CI: 4.03, 11.89). However, in the dialysis-dependent subgroup, there was no significant difference in the change in Hb levels or the Hb response rate between the roxadustat and ESA groups. There was no change in the mortality in the roxadustat group compared to that in the placebo/ESA group. Hyperkalemia may be a side effect of roxadustat.Conclusions: Roxadustat elevated the serum Hb levels in a manner similar to that observed for ESAs. Roxadustat raised the Hb levels more significantly than the placebo and showed a higher Hb response rate than the placebo group in NDD patients. Roxadustat is a safe and effective drug for anemia in CKD patients.

An Adaptive, Randomized, Placebo-Controlled, Double-Blind, Multi-Center Study of Oral FT-4202, a Pyruvate Kinase Activator in Patients with Sickle Cell Disease (PRAISE)

An Adaptive, Randomized, Placebo-Controlled, Double-Blind, Multi-Center Study of Oral FT-4202, a Pyruvate Kinase Activator in Patients with Sickle Cell Disease (PRAISE)

Efficacy of Intravenous Iron Replacement for Chemotherapy-Induced Anemia: A Prospective Phase II Pilot Study

Background: Iron deficiency anemia (IDA) is a common cancer-related complication, and intravenous (IV) iron administration has been reported to be effective in treating chemotherapy-induced anemia. This study aimed to evaluate the efficacy of IV iron administration without erythropoiesis-stimulating agents for anemia in cancer patients and to identify biomarkers for hemoglobin (Hb) response to predict the need for iron supplementation. Methods: This prospective single-arm phase II study enrolled solid cancer or lymphoma patients without bone marrow involvement. Patients received injection of IV ferric carboxymaltose (1000 mg) on the first day (visit 1) of chemotherapy or target therapy. Hb response, defined as an increase of ≥1·0 g/dL Hb, was assessed at visits one, two, and three. To identify predictive biomarkers of Hb response, transferrin saturation (TSAT) and levels of soluble transferrin receptor, hepcidin, erythropoietin, interleukin-6, and C-reactive protein were assessed at each visit. Findings: Of the 103 enrolled patients, 92 were eligible for analysis. Hb response was observed in 36 (39.1%), 53 (57.6%), and 61 (66.3%) patients at visits one, two, and three, respectively. After excluding 19 patients (20.6%) with absolute IDA, the Hb response rate was 83.5% (61/73). Regarding anemia-related biochemical parameters, Hb responders had significantly lower hepcidin levels than Hb non-responders (13.5 vs. 35.2 ng/mL; p=0.007). Upon comparing Hb response to the baseline hepcidin level, the low-hepcidin group contained significantly more responders than the high-hepcidin group (58/61 [95.1%] vs. 3/61 [4.9%]; p=0.002), based on a cutoff value of 34.1 ng/mL. Interpretation: IV iron supplementation increases Hb levels without serious adverse events in cancer patients receiving anticancer treatment. Furthermore, hepcidin is a useful biomarker for predicting functional IDA in cancer patients. These findings, however, need further validation. Funding: The study drug was provided by JW Pharmaceutical, Seoul, Republic of Korea. Declaration of Interest: The authors declare that they have no conflicts of interest concerning this article. Ethical Approval: The protocol was reviewed and approved by the institutional review board of Samsung Medical Center (IRB No. 2015-01-011), and the trial was conducted in accordance with the Declaration of Helsinki.

Oral sucrosomial iron versus intravenous iron in anemic cancer patients without iron deficiency receiving darbepoetin alfa: a pilot study

PurposeErythropoiesis-stimulating agents (ESAs) are often used in treatment of patients with chemotherapy-induced anemia. Many studies have demonstrated an improved hemoglobin (Hb) response when ESA is combined with intravenous iron supplementation and a higher effectiveness of intravenous iron over traditional oral iron formulations. A new formulation of oral sucrosomial iron featuring an increased bioavailability compared to traditional oral formulations has recently become available and could provide a valid alternative to those by intravenous (IV) route. Our study evaluated the performance of sucrosomial iron versus intravenous iron in increasing hemoglobin in anemic cancer patients receiving chemotherapy and darbepoetin alfa, as well as safety, need of transfusion, and quality of life (QoL).Materials and methodsThe present study considered a cohort of 64 patients with chemotherapy-related anemia (Hb >8 g/dL <10 g/dL) and no absolute or functional iron deficiency, scheduled to receive chemotherapy and darbepoetin. All patients received darbepoetin alfa 500 mcg once every 3 weeks and were randomly assigned to receive 8 weeks of IV ferric gluconate 125 mg weekly or oral sucrosomial iron 30 mg daily. The primary endpoint was to demonstrate the performance of oral sucrosomial iron in improving Hb response, compared to intravenous iron. The Hb response was defined as the Hb increase ≥2 g/dL from baseline or the attainment Hb ≥ 12 g/dL.ResultsThere was no difference in the Hb response rate between the two treatment arms. Seventy one percent of patients treated with IV iron achieved an erythropoietic response, compared to 70% of patients treated with oral iron. By conventional criteria, this difference is considered to be not statistically significant. There were also no differences in the proportion of patients requiring red blood cell transfusions and changes in QoL. Sucrosomial oral iron was better tolerated.ConclusionIn cancer patients with chemotherapy-related anemia receiving darbepoetin alfa, sucrosomial oral iron provides similar increase in Hb levels and Hb response, with higher tolerability without the risks or side effects of IV iron.

Combination with intravenous iron supplementation or doubling erythropoietin dose for patients with chemotherapy-induced anaemia inadequately responsive to initial erythropoietin treatment alone: study protocol for a randomised controlled trial

IntroductionErythropoietin (EPO) is a commonly used option in the treatment of chemotherapy-induced anaemia (CIA). However, ∼30–50% of patients fail to achieve an adequate response after initial treatment. Prior studies have...

Correction of Anemia with Continuous Erythropoietin Receptor Activator in Korean Patients on Long-Term Hemodialysis

Continuous erythropoietin receptor activator (CERA) is an erythropoietin with a long-half life. This study investigated the efficacy of CERA for correcting anemia in Korean patients on dialysis. Patients (≥18 yr) who were not receiving any ESAs for more than 8 weeks were randomly assigned to either intravenous CERA once every 2 weeks (n=39) or epoetin beta thrice-weekly (n=41) during a 24-week correction phase. Hemoglobin (Hb) response was defined as increase of Hb by at least 1 g/dL and Hb≥11 g/dL without red blood cell (RBC) transfusion. Median dialysis duration was 1.7 (0.3-20.8) and 1.6 (0.4-13.8) yr in CERA and epoetin beta group, respectively. Hemoglobin response rate of CERA was 79.5% (95% confidence interval [CI], 63.5-90.7). As the lower limit of 95% CI was higher than pre-specified 60% response rate, it can be concluded that CERA corrected anemia (P<0.05). Hb response rate of epoetin beta was 87.8% (95% CI, 73.8-95.9) (P=0.37). Median time to response was 12 weeks in CERA and 10.3 weeks in epoetin beta (P=0.03). It is suggested that once every 2 weeks administration of CERA is effective for correcting anemia in Korean patients on long-term hemodialysis with longer time-to-response than thrice weekly epoetin beta. (ClinicalTrials.gov registry No. NCT00546481)

Intravenous Iron Monotherapy for Absolute and Functional Iron Deficiency Anemia in Cancer Patients

AbstractAbstract 5167 ObjectiveIron deficiency anemia (IDA) is common in cancer patients. The Hemoglobin (Hb) response rate in cancer patients with IDA who receive an erythropoiesis stimulating agent (ESA) ranges from 25 – 65% and is increased to 68 – 93% when intravenous (IV) iron is added to the ESA. Interestingly, there have been no studies to date that have evaluated Hb response to IV iron monotherapy for the treatment of IDA in cancer patients. The National Comprehensive Cancer Network (NCCN) recommends treating absolute IDA (AIDA, serum ferritin < 30 ng/mL and TSAT < 15%) with iron monotherapy, preferably IV. However, the NCCN recommends that functional IDA (FIDA, serum ferritin ≤ 800 ng/mL and TSAT < 20%) be treated with both IV iron plus an ESA. Unfortunately, ESAs carry black box warnings for increased mortality, cancer progression, and venous thromboembolism. Therefore, it is important to explore other ways to more safely treat IDA in cancer patients. The objective of this study was to evaluate the Hb response rate to IV iron monotherapy in cancer patients with AIDA and FIDA. MethodsA retrospective chart review was performed at the Huntsman Cancer Institute between January 2006 and June 2011 in cancer patients with AIDA or FIDA who were treated with low molecular weight iron dextran (LMWID) monotherapy. Patients were excluded if they had a ferritin > 800 ng/mL or TSAT ≥ 20%, received an ESA within 6 weeks prior to or within 4 weeks after the LMWID infusion, or received a packed red blood cell transfusion prior to the LMWID infusion without a documented post- transfusion, pre-LMWID infusion Hb. The primary outcome was the proportion of patients with a Hb response defined as an increase of at least 1 g/dL within 6 weeks post IV iron infusion. The secondary outcome was the Hb response within 6 weeks stratified by dose of IV iron. ResultsTwo hundred patients received LMWID at our institution within the specified time period. However, 182 patients were excluded because they did not have active cancer, did not have a definitive diagnosis of AIDA or FIDA, or received concomitant therapy with an ESA. Eighteen patients with either a hematologic or solid malignancy were included. Thirteen patients had AIDA and 5 patients had FIDA. Eight of the 13 (62%) patients in the AIDA group had a Hb response. The median Hb increase in the AIDA group was 1. 3 g/dL (p < 0. 0001). A Hb response was observed in 4 of the 5 (80%) patients in the FIDA group. The median Hb increase in the FIDA group was 1. 8 g/dL (p = 0. 0224). Of the 8 patients with AIDA achieving a response, 4 received less than and 4 received more than the calculated total IV iron dose (equation per package insert). Of the 4 patients achieving a Hb response in the FIDA group, 3 received less than and 1 received equal to the calculated total dose. The overall Hb response rate to IV iron monotherapy for both groups was roughly 67% which is greater than the Hb response rate reported with ESAs alone. See Table 1 for individual patient details. ConclusionAlthough our study has limited patient numbers, this is the first data suggesting that IV iron without an ESA may be an effective treatment for both AIDA and FIDA in anemic patients with a variety of malignancies. IV iron monotherapy may eliminate the need for an ESA. This hypothesis should be tested in larger studies.Table 1:Individual Patient Baseline Demographics and Hb ChangeType of CancerFerritin (ng/mL)TSAT (%)Baseline Hb (g/dL)LMWID dose (gm) infusedCalculated LMWID dose (gm)% of TDI givenHb (g/dL) ≤ 6 weeksHb (g/dL) ChangeAbsolute IDAColorectal1548.821.314512.2+3.4Plasmacytic lymphoma2647.4221008.3+0.9GIST1049.211.56310.5+1.3MM12611.711.46812.3+0.6DLBCL1869.22.2211310.5+1.3MM961211.56811.7-0.3CMML2278.621.216410.9+2.3MM1098.60.823910.4+1.8Inflammatory breast1849.621.315411.3+1.7NSCLC1858.4221009.1+0.7Esophageal1039.611.75812+2.4NSCLC2249.111.85410.9+1.8Colorectal2957.61.12.3478.5+0.9Functional IDACMML4159.51.51.88611.4+1.9Bladder1356101110011.4+1.4Esophageal1981110.111.8579.9-0.2Rectal152199.311.75911.1+1.8MM62159.30.81.94212.7+3.4CMML = chronic myelomonocytic leukemia, DLBCL = diffuse large b-cell lymphoma, GIST = gastrointestinal stromal tumor, Hb = hemoglobin, LMWID = low molecular weight iron dextran, MM = multiple myeloma, NSCLC = non-small cell lung cancer. Disclosures:Off Label Use: The total dose infusion of low molecular weight iron dextran is not an FDA approved dosing regimen. However, it is commonly used in practice and has been used in other studies. Rodgers:American Regent: Consultancy.

Use of Biosimilar Epoetin to Increase Hemoglobin Levels in Patients with Chemotherapy-Induced Anemia: Real-Life Clinical Experience

To evaluate the effectiveness of a biosimilar erythropoiesis-stimulating agent (Binocrit) for the treatment of patients with cancer and chemotherapy-induced anemia in real-life clinical practice. Data were collected retrospectively from patients at five European centers (in France, Italy, The Netherlands, Romania and Spain) who received treatment with Binocrit. Hemoglobin (Hb) levels were recorded at regular intervals during Binocrit therapy for up to 26 weeks. Hb response (an increase of ≥ 1 g/dl in 4 weeks or a Hb level in the range 10-12 g/dl during the study) was assessed in patients with a Hb level ≥ 8.5 g/dl at the start of therapy who received treatment for at least 6 weeks. Hb response rates in patients who did and did not receive intravenous (iv.) iron were also assessed, and data on any serious unexpected adverse events were collected. Among evaluable patients (n = 113), 79% achieved a Hb response. Response rates were similar among evaluable patients who received an initial Binocrit dose of 30,000 or 40,000 IU/week (81 vs 78%; p = not significant). The Hb response rate was significantly greater in patients who received iv. iron than in patients who did not receive iv. iron (93 vs 77%; p < 0.05). No serious unexpected adverse events were reported. Use of the biosimilar erythropoiesis-stimulating agent Binocrit is effective and safe for the treatment of patients with cancer and chemotherapy-induced anemia. Supplementation with iv. iron increases the response rate compared with oral or no iron supplementation.

C.E.R.A. once every 4 weeks corrects anaemia and maintains haemoglobin in patients with chronic kidney disease not on dialysis

Background. No previous randomized controlled studies have been reported examining de novo, once every 4 weeks (Q4W) administration of erythropoiesis-stimulating agents in chronic kidney disease (CKD) patients. We report results from a randomized multinational study that compared continuous erythropoietin receptor activator (C.E.R.A.) Q4W with darbepoetin alfa once weekly (QW) or every 2 weeks (Q2W) for the correction of anaemia in non-dialysis CKD patients.Methods. Patients were randomized (1:1) to receive either 1.2 μg/kg C.E.R.A. Q4W or darbepoetin alfa QW/Q2W during a 20-week correction period and an 8-week evaluation period. Two primary end points were assessed: the haemoglobin (Hb) response rate and the change in average Hb concentration between baseline and evaluation.Results. The Hb response rate for C.E.R.A. was 94.1%, significantly higher than the protocol-specified 60% response rate [95% confidence interval (CI): 89.1, 97.3; P < 0.0001] and comparable with darbepoetin alfa (93.5%; 95% CI: 88.4, 96.8; P < 0.0001). C.E.R.A. Q4W was non-inferior to darbepoetin alfa QW/Q2W, with similar mean Hb changes from baseline of 1.62 g/dL and 1.66 g/dL, respectively. Patients receiving C.E.R.A. showed a steady rise in Hb, with fewer patients above the target range during the first 8 weeks compared with darbepoetin alfa [39 patients (25.8%) versus 72 patients (47.7%); P < 0.0001]. Adverse event rates were comparable between the treatment groups.Conclusion. C.E.R.A. Q4W successfully corrects anaemia and maintains stable Hb levels within the recommended target range in non-dialysis CKD patients.

Erythropoiesis-stimulating agents in the treatment of anaemia in cancer patients: ESMO Clinical Practice Guidelines for use

Erythropoiesis-stimulating agents in the treatment of anaemia in cancer patients: ESMO Clinical Practice Guidelines for use

Erythropoiesis-stimulating agents in cancer patients: ESMO Recommendations for use

Erythropoiesis-stimulating agents in cancer patients: ESMO Recommendations for use

Should Intravenous Iron Be the Standard of Care in Oncology?

Should Intravenous Iron Be the Standard of Care in Oncology?