Two-year long safety and efficacy of deferasirox film-coated tablets in patients with thalassemia or lower/intermediate risk MDS: phase 3 results from a subset of patients previously treated with deferasirox in the ECLIPSE study

Background: Despite the proven benefits of iron chelation therapy (ICT) in the management of chronic iron overload and related complications, compliance to long-term ICT is challenging. Results from the ECLIPSE study, an open-label, randomized, multicenter, 2-arm, phase 2 study evaluated the safety of deferasirox dispersible tablet and film-coated tablet (FCT) formulations in patients with transfusion-dependent thalassemia (TDT) or very low, low, or intermediate risk myelodysplastic syndrome (MDS) treated over 24 weeks. Methods: The aim of the current study (a 2-year, open-label, multicenter, single-arm, phase 3 study) is to evaluate the long-term safety and efficacy of deferasirox FCT in a subset of patients with TDT or lower/intermediate-risk MDS treated for 2 years after the completion of 24 weeks of treatment with deferasirox in the ECLIPSE phase 2 study. Results: Of 53 patients enrolled, 34 (64.2%) completed treatment and study. Adverse events (AEs) reported in most patients (similar to 70%) were of mild to moderate severity. Headache and diarrhea were the most frequently (> 25%) reported AEs. None of the serious AEs (including 1 death) were considered treatment related. No new safety signal was identified, and long-term safety of deferasirox FCT was consistent with the known safety profile of deferasirox. No major concerns associated with gastrointestinal tolerability, renal safety, or hematological abnormalities (thrombocytopenia/neutropenia) were reported during the 2 years. Patients receiving deferasirox FCT had a treatment compliance (by pill count) of similar to 90% and persistence (continuous use for >= 30 days) of > 95%. Reduction in serum ferritin level was almost consistent starting from week 2 across all post-baseline time points (relative reduction: month 6, 19%; month 12, 29%). Conclusions: The results from this 2-year interventional study suggest that the recommended dosing of deferasirox FCT, with better tolerability, palatability, and compliance, offers a favorable option of ICT for long-term management of iron overload and associated complications in TDT

Patient-reported outcomes from a randomized phase II study of the deferasirox film-coated tablet in patients with transfusion-dependent anemias

Background: Adherence to long-term chelation therapy in transfusion-dependent patients is critical to prevent iron overload-related complications. Once-daily deferasirox dispersible tablets (DT) have proven long-term efficacy and safety in patients ≥2 years old with chronic transfusional iron overload. However, barriers to optimal adherence remain, including palatability, preparation time, and requirements for fasting state. A new film-coated tablet (FCT) formulation was developed, swallowed once daily (whole/crushed) with/without a light meal. Methods: The open-label, Phase II ECLIPSE study evaluated patient-reported outcomes (PROs) in transfusion-dependent thalassemia or lower-risk myelodysplastic syndromes patients randomized 1:1 to receive deferasirox DT or FCT over 24 weeks as a secondary outcome of the study. Three PRO questionnaires were developed to evaluate both deferasirox formulations: 1) Modified Satisfaction with Iron Chelation Therapy Questionnaire; 2) Palatability Questionnaire; 3) Gastrointestinal (GI) Symptom Diary. Results: One hundred seventy three patients were enrolled; 87 received the FCT and 86 the DT formulation. FCT recipients consistently reported better adherence (easier to take medication, less bothered by time to prepare medication and waiting time before eating), greater satisfaction/preference (general satisfaction and with administration of medicine), and fewer concerns (less worry about not swallowing enough medication, fewer limitations in daily activities, less concern about side effects). FCT recipients reported no taste or aftertaste and could swallow all their medicine with an acceptable amount of liquid. GI summary scores were low for both formulations. Conclusions: These findings suggest a preference in favor of the deferasirox FCT formulation regardless of underlying disease or age group. Better patient satisfaction and adherence to chelation therapy may reduce iron overload-related complications. Trial registration: ClinicalTrials.gov identifier: NCT02125877; registered April 26, 2014

New film-coated tablet formulation of deferasirox is well tolerated in patients with thalassemia or lower-risk MDS: Results of the randomized, phase II ECLIPSE study

Once-daily deferasirox dispersible tablets (DT) have a well-defined safety and efficacy profile and, compared with parenteral deferoxamine, provide greater patient adherence, satisfaction, and quality of life. However, barriers still exist to optimal adherence, including gastrointestinal tolerability and palatability, leading to development of a new film-coated tablet (FCT) formulation that can be swallowed with a light meal, without the need to disperse into a suspension prior to consumption. The randomized, open-label, phase II ECLIPSE study evaluated the safety of deferasirox DT and FCT formulations over 24 weeks in chelation-naïve or pre-treated patients aged ≥10 years, with transfusion-dependent thalassemia or IPSS-R very-low-, low-, or intermediate-risk myelodysplastic syndromes. One hundred seventy-three patients were randomized 1:1 to DT (n = 86) or FCT (n = 87). Adverse events (overall), consistent with the known deferasirox safety profile, were reported in similar proportions of patients for each formulation (DT 89.5%; FCT 89.7%), with a lower frequency of severe events observed in patients receiving FCT (19.5% vs. 25.6% DT). Laboratory parameters (serum creatinine, creatinine clearance, alanine aminotransferase, aspartate aminotransferase and urine protein/creatinine ratio) generally remained stable throughout the study. Patient-reported outcomes showed greater adherence and satisfaction, better palatability and fewer concerns with FCT than DT. Treatment compliance by pill count was higher with FCT (92.9%) than with DT (85.3%). This analysis suggests deferasirox FCT offers an improved formulation with enhanced patient satisfaction, which may improve adherence, thereby reducing frequency and severity of iron overload-related complications

New film-coated tablet formulation of deferasirox is well tolerated in patients with thalassemia or lower-risk MDS: Results of the randomized, phase II ECLIPSE study

Once-daily deferasirox dispersible tablets (DT) have a well-defined safety and efficacy profile and, compared with parenteral deferoxamine, provide greater patient adherence, satisfaction, and quality of life. However, barriers still exist to optimal adherence, including gastrointestinal tolerability and palatability, leading to development of a new film-coated tablet (FCT) formulation that can be swallowed with a light meal, without the need to disperse into a suspension prior to consumption. The randomized, open-label, phase II ECLIPSE study evaluated the safety of deferasirox DT and FCT formulations over 24 weeks in chelation-naïve or pre-treated patients aged ≥10 years, with transfusion-dependent thalassemia or IPSS-R very-low-, low-, or intermediate-risk myelodysplastic syndromes. One hundred seventy-three patients were randomized 1:1 to DT (n = 86) or FCT (n = 87). Adverse events (overall), consistent with the known deferasirox safety profile, were reported in similar proportions of patients for each formulation (DT 89.5%; FCT 89.7%), with a lower frequency of severe events observed in patients receiving FCT (19.5% vs. 25.6% DT). Laboratory parameters (serum creatinine, creatinine clearance, alanine aminotransferase, aspartate aminotransferase and urine protein/creatinine ratio) generally remained stable throughout the study. Patient-reported outcomes showed greater adherence and satisfaction, better palatability and fewer concerns with FCT than DT. Treatment compliance by pill count was higher with FCT (92.9%) than with DT (85.3%). This analysis suggests deferasirox FCT offers an improved formulation with enhanced patient satisfaction, which may improve adherence, thereby reducing frequency and severity of iron overload-related complications

Nephrological Complications in Hemoglobinopathies: SITE Good Practice

Background. Hemoglobinopathies, among which thalassemic syndromes (transfusion-dependent and non-transfusion dependent thalassemias) and sickle cell disease (SCD), are the most widespread monogenic diseases worldwide. Hemoglobinopathies are endemic and spread-out all-over Italy, as result of internal and external migration flows. Nowadays, the increase therapeutic options associated to the general aging of patients with hemoglobinopathies related to the improvement in clinical management, contribute to the abnormalities in kidney function going from blood and urine test alterations to chronic kidney disease and end stage renal disease. Methods. Here, we carried out a revision of the literature as panel of recognized experts in hemoglobinopathies with the consultancy and the revision of two nephrologists on kidney alteration and kidney disease in patients with TDT, NTDT and SCD. This is part of the action of the Italian society for the study of thalassemia and hemoglobinopties (SITE). The purpose of this “good practice (GP)” is to provide recommendations for follow-up and therapy for the management of kidney alterations in patients with TDT, NTDT and SCD. The literature review covers the period 1.1.2016 to 31.12.2022. In consideration of the rarity of these diseases, the analysis was extended from 5 to 7 years. Moreover, in the absence of relevant scientific papers in the identified time frame, we referred to pivotal or population studies, when available. Finally, in the absence of evidence-based data from prospective and randomized trials, the authors had to refer to expert opinion (expert consensus) for many topics. Results. We generated question and answer boxes to offer a friendly consultation, using color code strategy and focused answers. Conclusions. The present GP will help in improving the clinical management, and the quality of care of patients with hemoglobinopathies

Liver disease in chelated transfusion-dependent thalassemics: the role of iron overload and chronic hepatitis C.

Abstract Iron overload and hepatitis virus C infection cause liver fibrosis in thalassemics. In a monocentric retrospective analysis of liver disease in a cohort of 191 transfusion-dependent thalassemics, in 126 patients who had undergone liver biopsy (mean age 17.2 years; 58 hepatitis virus C-RNA positive and 68 hepatitis virus C-RNA negative) the liver iron concentration (median 2.4 mg/gr dry liver weight) was closely related to serum ferritin levels (R = 0.58; p<0.0001). Male gender (OR 4.12) and serum hepatitis virus C-RNA positivity (OR 11.04) were independent risk factors for advanced liver fibrosis. The majority of hepatitis virus C-RNA negative patients with low iron load did not develop liver fibrosis, while hepatitis virus C-RNA positive patients infected with genotype 1 or 4 and iron overload more frequently developed advanced fibrosis. Hepatitis virus C infection is the main risk factor for liver fibrosis in transfusion-dependent thalassemics. Adequate chelation therapy usually prevents the development of liver fibrosis in thalassemics free of hepatitis virus C-infection and reduces the risk of developing severe fibrosis in thalassemics with chronic hepatitis C

Patient-reported outcomes from a randomized phase II study of the deferasirox film-coated tablet in patients with transfusion-dependent anemias

BACKGROUND: Adherence to long-term chelation therapy in transfusion-dependent patients is critical to prevent iron overload-related complications. Once-daily deferasirox dispersible tablets (DT) have proven long-term efficacy and safety in patients ≥2 years old with chronic transfusional iron overload. However, barriers to optimal adherence remain, including palatability, preparation time, and requirements for fasting state. A new film-coated tablet (FCT) formulation was developed, swallowed once daily (whole/crushed) with/without a light meal. METHODS: The open-label, Phase II ECLIPSE study evaluated patient-reported outcomes (PROs) in transfusion-dependent thalassemia or lower-risk myelodysplastic syndromes patients randomized 1:1 to receive deferasirox DT or FCT over 24 weeks as a secondary outcome of the study. Three PRO questionnaires were developed to evaluate both deferasirox formulations: 1) Modified Satisfaction with Iron Chelation Therapy Questionnaire; 2) Palatability Questionnaire; 3) Gastrointestinal (GI) Symptom Diary. RESULTS: One hundred seventy three patients were enrolled; 87 received the FCT and 86 the DT formulation. FCT recipients consistently reported better adherence (easier to take medication, less bothered by time to prepare medication and waiting time before eating), greater satisfaction/preference (general satisfaction and with administration of medicine), and fewer concerns (less worry about not swallowing enough medication, fewer limitations in daily activities, less concern about side effects). FCT recipients reported no taste or aftertaste and could swallow all their medicine with an acceptable amount of liquid. GI summary scores were low for both formulations. CONCLUSIONS: These findings suggest a preference in favor of the deferasirox FCT formulation regardless of underlying disease or age group. Better patient satisfaction and adherence to chelation therapy may reduce iron overload-related complications. TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT02125877; registered April 26, 2014

Italian patients with hemoglobinopathies exhibit a 5-fold increase in age-standardized lethality due to SARS-CoV-2 infection.

Since the beginning of the COVID-19 pandemic, concerns have been expressed worldwide for patients with hemoglobinopathies and their vulnerability to SARS-CoV-2 infection. Data from Lebanon confirmed a role of underlying comorbidities on COVID-19 severity, but no deaths among a cohort of thalassemia patients.1 Patients with sickle cell disease (SCD) displayed a broad range of severity after SARS-CoV-2 infection, spanning from a favorable outcome unless pre-existing comorbidities (UK cohort)2 to high case mortality in US.3 History of pain, heart, lung, and renal comorbidities was identified as risk factors of worse COVID-19 outcomes by the US SECURE-SCD Registry.4 While Italy experienced a death rate in the general population among the highest in the world, preliminary data from the first wave of the pandemic showed a lower than expected number of infected thalassemia patients (updated up to April 10, 2020), likely due to earlier and more vigilant self-isolation compared to the general population.

Myocardial iron overload in thalassaemia major. How early to check?

The age at which it is necessary to start Cardiovascular Magnetic Resonance (CMR) T2* screening in thalassaemia major (TM) is still uncertain. To clarify this point, we evaluated the prevalence of myocardial iron overload (MIO), function and fibrosis by CMR in TM patients younger than 10 years. We retrospectively selected 35 TM patients enrolled in the Myocardial Iron Overload in Thalassaemia network. MIO was measured by T2* multislice multiecho technique. Biventricular function parameters were evaluated by cine images. To detect myocardial fibrosis, late gadolinium enhancement images were acquired. Patients’ age ranged from 42 to 97 years. All scans were performed without sedation. Nine patients showed no MIO, 22 patients had heterogeneous MIO with a T2* global value ≥20 ms; two patients had heterogeneous MIO with a T2* global value <20 ms and two patients showed homogeneous MIO. No patient showed myocardial fibrosis. Among the patients with heart T2*<20 ms, the youngest was 6 years old, none showed heart dysfunction and the iron transfused was <35 g in all cases. Cardiac iron loading can occur much earlier than previously described. The first cardiac T2* assessment should be performed as early as feasible without sedation, especially if chelation is started late or if poor compliance is suspected