Comparison of efficacy and safety of thalidomide vs hydroxyurea in patients with Hb E-β thalassemia - a pilot study from a tertiary care Centre of India

Jain, Manisha; Chakrabarti, Prantar; Dolai, Tuphan Kanti; Ghosh, Pramit; Mandal, Prakas Kumar; Baul, Shuvra Neel; De, Rajib

doi:10.1016/j.bcmd.2021.102544

Cited by 10 publications

(7 citation statements)

References 12 publications

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“…A number of scholars pointed out that thalidomide induced γ-globin mRNA expression in a dose-dependent manner, while it had no effect on ß -globin expression ( Aerbajinai et al, 2007 ). Several small case series and clinical trials (12 single-arm and 3 randomized controlled trials) have reported the efficacy and safety of thalidomide in patients with ß -thalassemia ( Chen et al, 2017 ; Kalra et al, 2017 ; Li et al, 2018 ; Ren et al, 2018 ; Jain et al, 2019 ; Ricchi et al, 2019 ; Begum et al, 2020 ; Islam et al, 2020 ; Javed et al, 2020 ; Nag et al, 2020 ; Sen et al, 2020 ; Yang et al, 2020 ; Yassin, 2020 ; Chandra et al, 2021 ; Chen et al, 2021 ; Jain et al, 2021 ; Li et al, 2021 ). Chen et al conducted the largest prospective study enrolled 99 patients has shown remarkable response to thalidomide treatment for patients with ß -thalassemia ( Chen et al, 2021 ).…”

Section: Discussionmentioning

confidence: 99%

Investigating the Efficacy and Safety of Thalidomide for Treating Patients With ß-Thalassemia: A Meta-Analysis

Wei

Yang

et al. 2022

Front. Pharmacol.

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At present, the main therapies for ß-thalassemia patients include regular blood transfusion and iron chelation, associating with a number of limitations. Thalidomide, a fetal hemoglobin (HbF) inducer that promotes γ-globin gene expression, has been reported to be effective for ß-thalassemia. Thus, this meta-analysis was conducted to assess the efficacy and safety of thalidomide for treating patients with ß-thalassemia. We searched the related studies from eight databases published from inception until December 1, 2021. The R 4.0.5 language programming was used to perform meta-analysis. After screening of retrieved articles, 12 articles were included that enrolled a total of 451 patients. The Cochrane Collaboration risk assessment tool was used to evaluate the quality and the bias risk of the randomized controlled trials (RCTs), and non randomized trials were assessed using Newcastle-Ottawa Scale (NOS). After treatment with thalidomide, the pooled overall response rate (ORR) was 85% (95% confidence interval (CI): 80–90%), and the pooled complete response rate (CRR) was 54% (95% confidence interval: 31–76%). Compared with the placebo group, the thalidomide group had higher odds of overall response rate (odds ratio = 20.4; 95% CI: 6.75–61.64) and complete response rate (odds ratio = 20.4; 95% CI: 6.75–61.64). A statistically significant increase in hemoglobin level and HbF level after treatment, while there was no statistically significant difference in adult hemoglobin (HbA) level, spleen size, and serum ferritin. According to the results of ORR and CRR, transfusion-dependent thalassemia (TDT) patients showed remarkable efficacy of thalidomide, 83 and 52% respectively. So we analyzed 30 transfusion-dependent thalassemia patients from three studies and found that the most frequent ß-globin gene mutations were CD41-42 (-TCTT), while response to thalidomide did not show any statistically significant relationship with XmnI polymorphism or CD41-42 (-TCTT) mutation. About 30% of patients experienced mild adverse effects of thalidomide. Collectively, thalidomide is a relatively safe and effective therapy to reduce the blood transfusion requirements and to increase Hb level in patients with ß-thalassemia.

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Section: Discussionmentioning

confidence: 99%

Investigating the Efficacy and Safety of Thalidomide for Treating Patients With ß-Thalassemia: A Meta-Analysis

Wei

Yang

et al. 2022

Front. Pharmacol.

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“…47 Thalidomide has also been associated with hematologic responses in both NTDT and TDT patients in observational studies and small trials from India or China. [48][49][50][51][52][53][54][55] Polymorphisms in HBG2 and HBS1L-MYB contributed significantly to thalidomide response in these patients. 56 Larger clinical trials with thalidomide in TDT patients are ongoing in Pakistan (NCT03651102)…”

Section: Fetal Hemoglobin Inducing Agentsmentioning

confidence: 91%

“…Studies from Italy have conversely shown limited durability of response 47 . Thalidomide has also been associated with hematologic responses in both NTDT and TDT patients in observational studies and small trials from India or China 48–55 . Polymorphisms in HBG2 and HBS1L‐MYB contributed significantly to thalidomide response in these patients 56 .…”

Section: Correction Of the α/Non‐α‐globin Chain Imbalancementioning

confidence: 99%

2021 update on clinical trials in β‐thalassemia

Musallam¹,

Bou‐Fakhredin

Cappellini

et al. 2021

American J Hematol

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The treatment landscape for patients with β-thalassemia is witnessing a swift evolution, yet several unmet needs continue to persist. Patients with transfusiondependent β-thalassemia (TDT) primarily rely on regular transfusion and iron chelation therapy, which can be associated with considerable treatment burden and cost.Patients with non-transfusion-dependent β-thalassemia (NTDT) are also at risk of significant morbidity due to the underlying anemia and iron overload, but treatment options in this patient subgroup are limited. In this review, we provide updates on clinical trials of novel therapies targeting the underlying pathology in β-thalassemia, including the α/non-α-globin chain imbalance, ineffective erythropoiesis, and iron dysregulation. | INTRODUCTIONThe β-thalassemias are a group of inherited disorders of hemoglobin (Hb) synthesis characterized by chronic anemia of varying severity.The degree of anemia relies on several genetic and environmental factors and determines the need for regular transfusion therapy. It is now common practice to classify patients as having transfusion-The TDT patients (β-thalassemia major and severe forms of HbE/β-thalassemia) are those who commonly present in early childhood with severe anemia and require lifelong transfusion therapy for survival. 1 Although the introduction of transfusions improved survival in TDT patients, it did not come without its own side-effect, systemic iron overload leading to end-organ damage and increased mortality from cardiac or hepatic disease. [2][3][4] Advances in iron chelation therapy and the introduction of MRI techniques to detect organ-specific iron overload have led to improved management and patient outcomes. 5,6 Still, TDT comes with considerable burden to the patient, clinician, and overall healthcare system owing to persistent morbidity and high healthcare utilization, poor access to optimal care and high treatment cost especially in resource-limited countries, and several unmet needs in terms of efficacy, safety and adherence to conventional therapies. 7 Allogeneic hematopoietic stem-cell transplantation (HSCT) has been used successfully for the past few decades to offer curative therapy for patients with TDT, but is only available to a minority of patients with compatible donors. 1 Patients with NTDT (β-thalassemia intermedia and mildmoderate forms of HbE/β-thalassemia) usually present later in childhood or even in adolescence with mild-moderate anemia that does not require immediate placement on a regular transfusion program. 1,8 Progress made over the past few decades has indicated that the diagnosis of NTDT carries greater morbidity than previously recognized.Ineffective erythropoiesis and anemia have been linked to an array of morbidities stemming from chronic hypoxia and an established hypercoagulable state. 1 Patients with Hb levels < 10 g/dl are at an increased risk of morbidity development, and variations of 1 g/dl can change a patient's morbidity risk. 9,10 There are currently no approved agents for the management of anem...

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“…In vitro models of pathologic erythropoiesis have established that thalidomide might induce γ-globin mRNA expression in a dose-dependent manner throughout the modulation of γ-globin mRNA expression targeting BCL11A, SOX6, GATA1 and KLF1 as well as by post-translational modification induced by p38MAPK activation [82][83][84]. Several small case series and few observational studies have reported the efficacy and safety of thalidomide in patients with β-thalassemia [85][86][87][88][89][90][91][92]. Collectively, these studies show that thalidomide (range dosage from 75-100 mg/kg/day to 150-200 mg/kg/day) increases Hb levels by elevating the HbF level and reduces spleen size [93][94][95][96][97].…”

Section: Immunomodulators: Thalidomide and Its Derivativesmentioning

confidence: 99%

Pharmacological Induction of Fetal Hemoglobin in β-Thalassemia and Sickle Cell Disease: An Updated Perspective

et al. 2022

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A significant amount of attention has recently been devoted to the mechanisms involved in hemoglobin (Hb) switching, as it has previously been established that the induction of fetal hemoglobin (HbF) production in significant amounts can reduce the severity of the clinical course in diseases such as β-thalassemia and sickle cell disease (SCD). While the induction of HbF using lentiviral and genome-editing strategies has been made possible, they present limitations. Meanwhile, progress in the use of pharmacologic agents for HbF induction and the identification of novel HbF-inducing strategies has been made possible as a result of a better understanding of γ-globin regulation. In this review, we will provide an update on all current pharmacological inducer agents of HbF in β-thalassemia and SCD in addition to the ongoing research into other novel, and potentially therapeutic, HbF-inducing agents.

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Comparison of efficacy and safety of thalidomide vs hydroxyurea in patients with Hb E-β thalassemia - a pilot study from a tertiary care Centre of India

Cited by 10 publications

References 12 publications

Investigating the Efficacy and Safety of Thalidomide for Treating Patients With ß-Thalassemia: A Meta-Analysis

Investigating the Efficacy and Safety of Thalidomide for Treating Patients With ß-Thalassemia: A Meta-Analysis

2021 update on clinical trials in β‐thalassemia

Pharmacological Induction of Fetal Hemoglobin in β-Thalassemia and Sickle Cell Disease: An Updated Perspective

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