Thrombopoietin Receptor Agonist Research Articles

Frequency of CD40-1C>T polymorphism (rs1883832) and association with response to treatment in children with primary immune thrombocytopenia.

To investigate whether (cluster of differentiation) CD40-1C>T (rs1883832) contributes to predisposition and treatment response of primary immune thrombocytopenia (pITP) in children. A case-control study that included 100 children with newly diagnosed pITP and 50 age- and sex-matched healthy controls. CD40 rs1883832 was genotyped using TaqMan allele discrimination real-time polymerase chain reaction (PCR). Patients were categorized into responders and non-responders according to their response to corticosteroids and thrombopoietin-receptor agonists (TPO-RA) at 3-month intervals. The genotypic distribution of the CD40 rs1883832 was significantly different among cases and controls (CC 48% vs. 30%; CT 44% vs. 42%; TT 8% vs. 28%; p=.003). Compared with controls, children with newly diagnosed pITP had significantly higher C allele frequency (70% vs. 51%; odds ratio [OR] 2.2, 95% confidence interval [CI]: 1.3-3.8; p=.001). The association between C allele frequency and pITP risk was evident in females (OR 4.3, 95% CI: 2.1-8.8; p<.001), but not in males (OR 0.9, 95% CI: 0.4-2.1; p=.822). Compared with responders, the C allele frequency was significantly higher among non-responders to corticosteroids (87% vs. 66%; OR 3.4, 95% CI: 1.2-11.7; p=.012), but not to TPO-RA (92% vs. 85%; OR 2, 95% CI: 0.2-107; p=.550). CD40 rs1883832 polymorphism may contribute to predisposition and response to upfront corticosteroids therapy of pediatric pITP. These findings improve our understanding of the compound pathophysiology of ITP, suggest important clinical potentials, and open the door for further research on the mechanistic role of CD40 rs1883832 in ITP development and progression.

Treatment opportunities for refractory immune thrombocytopenia

Background. Primary immune thrombocytopenia (ITP) is an orphan disease characterized by decreased platelet count in the peripheral blood which in some cases can cause bleeding of varying severity. Currently, the use of thrombopoietin receptor agonists (TPO-RAs) is recommended as the second line therapy for ITP as it allows to achieve high platelet response (PR), including complete, in 73 % of cases of chronic ITP and in 87 % of cases of newly diagnosed disease. The mechanism of action differs for different TPO-RAs. Given this fact, in cases of resistance or intolerance to therapy with one TPO-RA, attempts are made to switch to another. The effectiveness of this approach for overcoming ITP resistance varies from 50 to 93 % according to various publications. Aim. To assess the ability to achieve and maintain PR by switching from one TPO-RA to another in cases of resistance to the previous TPO-RA used in the second or subsequent lines of therapy. Materials and methods. The analysis included 59 patients who were resistant (in 2 cases intolerance was also noted) to TPO-RA therapy (received after standard therapy) who were prescribed TPO-RA treatment with a different mechanism of action: switch from romiplostim to eltrombopag (25 patients) or vice versa (34 patients). Both groups were comparable in terms of demographic characteristics and median platelet level at the time of TPO-RA switching. Results. PR was obtained in 76 % of cases, including complete response in 54 %, as a result of switching from one TPO-RA to another in 59 patients. Among 34 patients switched from eltrombopag to romiplostim, PR was achieved in 31 (91 %) patients, including complete response in 22 (65 %). Romiplostim was switched to eltrombopag in 25 patients, PR was achieved in 14 (56 %) with complete response in 10 (40 %). Conclusion. The study showed that PR can be achieved and maintained through switching from one TPO-RA to an alternative.

Expansion effect of romiplostim on hematopoietic stem and progenitor cells versus thrombopoietin and eltrombopag

Romiplostim, a thrombopoietin (TPO) receptor agonist, is a clinically approved drug that is clearly effective in reconstituting hematopoiesis in refractory aplastic anemia and idiopathic thrombocytopenic purpura. However, the mechanism underlying its biological effect is unknown, and its differences from other TPO receptor agonists remain unclear. Therefore, we determined the in vitro expansion effect of romiplostim on human CD34 + hematopoietic stem and progenitor cells (HSPCs) versus recombinant human TPO (rhTPO) and another clinically available drug, eltrombopag. We also performed single-cell RNA-seq to determine effects of romiplostim on CD34 + HSPCs at the molecular level. The maximum expansion effect of romiplostim on total CD34 + cells, CD34 + CD38 + progenitor cells, and CD34 + CD38 − immature cells was comparable to that of rhTPO, but higher than that of eltrombopag, particularly on CD34 + CD38 − immature cells. Single-cell RNA-seq analysis revealed that both romiplostim and eltrombopag induced signatures driven by rhTPO, but romiplostim induced molecular changes related to RHOA signaling in the most primitive HSPC subsets that were partially driven or not driven by eltrombopag. Additionally, romiplostim did not induce TFRC expression as was observed with eltrombopag. In conclusion, romiplostim expands and affects human HSPCs similar to rhTPO, but partially different from eltrombopag in terms of induction of gene expression.

Diagnosis and Management of Immune Thrombocytopenia in Paediatrics: A Comprehensive Review.

Immune thrombocytopenia (ITP) in paediatric patients is a complex and heterogeneous disorder characterized by isolated thrombocytopenia and an increased risk of bleeding. The diagnosis of ITP involves a careful exclusion of other causes of thrombocytopenia, supported by clinical evaluation and laboratory findings. Management strategies have evolved significantly, emphasizing individualized treatment approaches based on disease severity, bleeding risk, and patient-specific factors. This comprehensive review provides an in-depth analysis of the current diagnostic criteria, including the role of novel biomarkers and genetic testing in distinguishing ITP from other haematological disorders. We also explore the latest therapeutic options, ranging from observation and first-line treatments such as corticosteroids and intravenous immunoglobulin (IVIG) to second-line therapies, including thrombopoietin receptor agonists and immunosuppressive agents. The review addresses the challenges of managing chronic ITP in pediatric patients, focusing on balancing treatment efficacy with the potential side effects and long-term outcomes. Additionally, we discuss the emerging role of personalized medicine in optimizing care for children with ITP, highlighting recent advances in targeted therapies and the potential for future research to refine diagnostic and treatment paradigms to refine diagnostic and treatment paradigms further.

Thrombopoietin Receptor Agonists as Second-Line Treatment in Children With Ongoing Immune Thrombocytopenia

What Is the Issue? Immune thrombocytopenia (ITP) is an autoimmune disorder characterized by low platelets and an increase in bleeding risk; in the pediatric population, the reported incidence rate varies between 2 and 5 per 100,000 children per year. Spontaneous remission may be observed in up to 70% of patients, while 20% of patients may experience severe bleeding symptoms. In children whose ITP does not respond to first-line corticosteroids, IV immunoglobulin (IVIG), or anti-D immunoglobulin, guidelines recommend the use of thrombopoietin receptor agonists (TPO-RAs), i.e., eltrombopag or romiplostim (avatrombopag did not have a marketing authorization and Notice of Compliance at the time that the review was initiated). Rituximab is considered a subsequent-line of therapy. Splenectomy is not usually considered an appropriate treatment option in children. The goal of therapy in pediatric patients with ITP is to reduce bleeding and improve quality of life. Platelet response is considered a valid and appropriate surrogate end point in studies and routine assessment in clinical practice. Children whose ITP does not respond to available first-line drugs may require subsequent treatment with off-label drugs because they do not have access to TPO-RAs. What Did We Do? We searched key resources, including journal citation databases, and conducted a focused internet search for relevant evidence. A systematic review of the literature identified 5 studies (4 randomized controlled trials [RCTs] and 1 observational study), which were synthesized narratively. The review addressed the following policy questions: In children with ongoing, active ITP, what is the overall body of evidence supporting the use of TPO-RAs and rituximab after failure of first-line therapies? Based on the level and quality of clinical evidence, should TPO-RAs be reimbursed for use earlier in the treatment sequencing for children with ongoing, active ITP, instead of being reimbursed only after a course of rituximab? What Did We Find? Evidence from 2 RCTs (n = 159) suggests that eltrombopag likely increases and maintains platelet response over time, in addition to decreasing the use of rescue medication and clinically significant bleeding compared to placebo, which were considered clinically meaningful outcomes for pediatric patients with ITP. There was a low risk of bias in the studies, but uncertainty was introduced due to the small sample sizes. Evidence from 1 RCT (n = 62) suggests that romiplostim may also increase and maintain platelet response, as well as reduce clinically significant bleeding compared to placebo. However, there was some concern due to a high risk of bias in the studies and uncertainty due to the small sample size, which suggests a need for caution in the interpretation of the findings. The effectiveness of rituximab was inconclusive due to the lack of evidence, as no comparative RCTs could be identified, while the observational study included presented only descriptive comparisons. No evidence was identified in support of trying rituximab before accessing TPO-RAs. What Does This Mean? Given that ITP is rare in children, there is a gap in available relevant evidence, and robust evidence from large RCTs in this patient population are unlikely to be conducted. Jurisdictions may consider requesting an implementation advice panel for use of eltrombopag and romiplostim after failure of first-line therapies in children with ongoing, active ITP.

Clinical characteristics, treatment, and outcomes of nivolumab induced immune thrombocytopenia.

Immune thrombocytopenia (ITP) represents an uncommon hematological side effect associated with nivolumab, and its distinct clinical attributes remain poorly defined. This research aimed to explore the clinical manifestations and outcomes of ITP induced by nivolumab. Reports on nivolumab induced ITP up to April 30, 2024, were collected for retrospective analysis. The study involved 34 patients with a median age of 67 years (range 32, 82). The onset of ITP varied from 10 to 100 days post initial dosage, with a median onset at 70 days. The majority of patients exhibited no symptoms, with only 23.5% experiencing clinically significant bleeding and 11.8% facing non-clinically significant bleeding. The median platelet count was 12 × 109/L (range 0, 115), with 67.6% of patients having platelet levels below 25 × 109/L. Bone marrow biopsy revealed mainly elevated megakaryocytes. Platelet-associated IgG levels were elevated with a median of 210 ng/107 cells (range 73, 1130). Subsequent interventions, which included cessation of nivolumab, administration of systemic corticosteroids, intravenous immunoglobulin therapy, a thrombopoietin receptor agonist, platelet transfusion, and rituximab treatment, resulted in 82.4% of subjects achieving normalized platelet counts, whereas 5.9% passed away due to ITP. ITP is a rare life-threatening immune-related adverse event and necessitates close monitoring. Systemic steroids are the primary treatment for ITP, while intravenous immunoglobulin, thrombopoietin receptor agonist and rituximab are other options.

Efficacy and safety of avatrombopag in the treatment of thrombocytopenia after umbilical cord blood transplantation.

Delayed platelet engraftment is a common complication after umbilical cord blood transplantation (UCBT), and there is no standard therapy. Avatrombopag (AVA) is a second-generation thrombopoietin (TPO) receptor agonist (TPO-RA) that has shown efficacy in immune thrombocytopenia (ITP). However, few reports have focused on its efficacy in patients diagnosed with thrombocytopenia after allogeneic hematopoietic stem cell transplantation (allo-HSCT). We conducted a retrospective study to evaluate the efficacy of AVA as a first-line TPO-RA in 65 patients after UCBT; these patients were compared with 118 historical controls. Response rates, platelet counts, megakaryocyte counts in bone marrow, bleeding events, adverse events and survival rates were evaluated in this study. Platelet reconstitution differences were compared between different medication groups. Multivariable analysis was used to explore the independent beneficial factors for platelet implantation. Fifty-two patients were given AVA within 30days post-UCBT, and the treatment was continued for more than 7days to promote platelet engraftment (AVA group); the other 13 patients were given AVA for secondary failure of platelet recovery (SFPR group). The median time to platelet engraftment was shorter in the AVA group than in the historical control group (32.5days vs. 38.0days, Z=2.095, P=0.036). Among the 52 patients in the AVA group, 46 achieved an overall response (OR) (88.5%), and the cumulative incidence of OR was 91.9%. Patients treated with AVA only had a greater 60-day cumulative incidence of platelet engraftment than patients treated with recombinant human thrombopoietin (rhTPO) only or rhTPO combined with AVA (95.2% vs. 84.5% vs. 80.6%, P<0.001). Patients suffering from SFPR had a slightly better cumulative incidence of OR (100%, P=0.104). Patients who initiated AVA treatment within 14days post-UCBT had a better 60-day cumulative incidence of platelet engraftment than did those who received AVA after 14days post-UCBT (96.6% vs. 73.9%, P=0.003). In summary, compared with those in the historical control group, our results indicate that AVA could effectively promote platelet engraftment and recovery after UCBT, especially when used in the early period (≤14days post-UCBT).

Platelet transfusion.

Platelet transfusions, used as prophylaxis or treatment for bleeding, are potentially life-saving. In many countries, demand for platelet transfusion is rising. Platelets are a limited and costly resource, and it is vital that they are used appropriately. This study will explore the evidence behind platelet transfusions in different contexts, in particular recent and important research in this area. Recent randomized clinical trials demonstrate the efficacy of platelet transfusions in some contexts but potential detrimental effects in others. Platelet transfusions also carry risk of transfusion reactions, bacterial contamination and platelet transfusion refractoriness. Observational and clinical studies, which highlight approaches to mitigate these risks, will be discussed. There is growing interest in cold-stored or cryopreserved platelet units, which may improve platelet function and availability. Clinical trials also highlight the efficacy of other supportive measures such as tranexamic acid or thrombopoietin receptor agonists in patients with bleeding. Although platelet transfusions are beneficial in many patients, there remain many settings in which the optimal use of platelet transfusions is unclear, and some situations in which they may have detrimental effects. Future clinical trials are needed to determine optimal use of platelet transfusions in different patient populations.

Is there a role for eltrombopag drug levels in paediatric immune thrombocytopenia management?

Paediatric immune thrombocytopenia treatment was revolutionized with the advent of the thrombopoietin mimetics romiplostim and eltrombopag. For eltrombopag, dosing recommendations have been based on patients' ages (with dose reductions for those with hepatic impairment and for some of East Asian ethnicity) and titrated based on platelet counts and adverse drug reactions. However, it is clear that identical eltrombopag dosing for paediatric patients can result in variable side effects and platelet counts, raising the question as to whether variable eltrombopag plasma concentrations are responsible for these differing drug responses. Commentary on: Dong etal. Exploratory study on the individualized application of eltrombopag in paediatric immune thrombocytopenia guided by therapeutic drug monitoring. Br J Haematol 2024; 205:1930-1937.

Use of Eltrombopag to Improve Thrombocytopenia and Tranfusion Requirement in Anti-CD19 CAR-T Cell-Treated Patients.

Background/Objectives: Immune effector cell-associated hematotoxicity (ICAHT) is a frequent adverse event after chimeric antigen receptor (CAR)-T cell therapy. Grade ≥ 3 thrombocytopenia occurs in around one-third of patients, and many of them become platelet transfusion-dependent. Eltrombopag is a thrombopoietin receptor agonist (TPO-RA) able to accelerate megakaryopoiesis, which has been used successfully in patients with bone marrow failure and immune thrombocytopenia (ITP). Its role in managing thrombocytopenia and other cytopenias in CAR-T cell-treated patients has been scarcely addressed. Our aim was to report the safety and efficacy of this approach in patients included in the Spanish Group for Hematopoietic Transplantation and Cellular Therapy (GETH-TC) registry. Methods: This is a retrospective, multicenter, observational study. Patients who developed platelet transfusion dependence subsequently to CAR-T cells and received eltrombopag to improve platelet counts were recruited in 10 Spanish hospitals. Results: Thirty-eight patients were enrolled and followed up for a median (interquartile range [IQR]) of 175 (99, 489) days since CAR-T cell infusion. At the moment eltrombopag was indicated, 18 patients had thrombocytopenia and another severe cytopenia, while 8 patients had severe pancytopenia. After 32 (14, 38) days on eltrombopag, 29 (76.3%) patients recovered platelet transfusion independence. The number of platelet units transfused correlated with the time needed to restore platelet counts higher than 20 × 109/L (Rho = 0.639, p < 0.001). Non-responders to eltrombopag required more platelet units (58 [29, 69] vs. 12 [6, 26] in responders, p = 0.002). Nineteen out of twenty-three (82.6%) patients recovered from severe neutropenia after 22 (11, 31) days on eltrombopag. Twenty-nine out of thirty-five (82.9%) patients recovered red blood cell (RBC) transfusion independence after 29 (17, 44) days. Seven patients recovered all cell lineages while on treatment. No thromboembolic events were reported. Only two transient toxicities (cholestasis, hyperbilirubinemia) were reported during eltrombopag treatment, none of which compelled permanent drug withdrawal. Conclusions: Eltrombopag could be safely used to manage thrombocytopenia and accelerate transfusion independence in CAR-T cell-treated patients.

Efficacy and Safety of Thrombopoietin Receptor Agonist (TPO-RA) in Patients with Chronic Liver Disease: A Systematic Review and Meta-Analysis

Context: The TPO-receptor agonist (TPO-RA) has been extensively studied for its use in thrombocytopenia. Objectives: We aimed to systematically analyze the efficacy and safety of TPO-RA in chronic liver disease patients. Methods: The study population consisted of adults with chronic liver disease. The intervention was TPO-RA. The primary outcome was the efficacy of TPO-RA (increase in thrombocyte levels and likelihood of avoiding thrombocyte transfusion pre-operatively), while the secondary outcome was the safety of TPO-RA. The demographics of the study and the usage of TPO-RA medications were used to classify the research. Results: This review consisted of 1529 chronic liver disease patients who received TPO-RA and 911 who received a comparator (placebo or thrombocyte transfusion). The TPO-RA significantly increased thrombocyte levels by 34.59 × 109/L (P &lt; 0.00001). The use of TPO-RA pre-procedure reduced the likelihood of pre-operative platelet transfusion and up to seven days following the scheduled procedure by 88% (P &lt; 0.00001). TPO-receptor agonist was not associated with all-cause mortality (P = 0.77) or an increase in thrombosis events, with a pooled OR of 1.36 (P = 0.43). According to a meta-regression analysis, the population may explain the heterogeneity. Subsequent leave-one-out sensitivity analysis of the thrombocyte level change after TPO-RA revealed that no single study was accountable for the heterogeneity of thrombocyte level changes. Conclusions: The use of TPO-RA increases the thrombocyte levels of chronic liver disease patients and reduces the odds of needing thrombocyte transfusion pre-operatively. TPO-receptor agonist is also safe to use, with no increase in mortality risk or thrombosis risk.

Plasma concentration of thrombopoietin in dogs with immune thrombocytopenia.

Immune thrombocytopenia (ITP) is a common cause of severe thrombocytopenia in dogs. The pathogenesis of nonassociative, primary ITP (pITP) appears complex, with ill-defined thrombopoietic response. Develop an immunoassay to measure plasma canine thrombopoietin (TPO) concentration and characterize TPO concentrations in dogs with pITP. Forty-one healthy dogs, 8 dogs in an induced ITP model (3 control, 5 ITP), and 58 pITP dogs. Recombinant canine TPO (rcTPO) was purchased and its identity confirmed by mass spectrometry. Monoclonal antibodies were raised to rcTPO and used to configure a sandwich ELISA using streptavidin-biotin detection. Assay performance, coefficients of variability, and healthy dog plasma TPO reference interval (RI) were determined, followed by assay of ITP samples. Assay dynamic range was 15 pg/mL (lower limit of detection) to 1000 pg/mL TPO, with limit of quantitation of 62 pg/mL. Plasma TPO RI was 0 to 158 pg/mL, with plasma TPO <62 pg/mL for 35/41 healthy dogs. All dogs with induced ITP developed marked increases in plasma TPO concentration. Peak values ranged from 515 to >6000 pg/mL. In contrast, only 2/58 pITP dogs had TPO values above RI. Plasma TPO concentration is paradoxically low at diagnosis for most dogs with pITP. This finding suggests that ineffective thrombopoiesis contributes to thrombocytopenia in pITP dogs and supports evaluating TPO receptor agonist treatment as used for pITP in humans. The TPO assay provides a new tool to study thrombopoiesis in pITP and other thrombocytopenic syndromes in dogs.

2025 update on clinical trials in immune thrombocytopenia.

Although the development and regulatory approval of the thrombopoietin receptor agonists revolutionized aspects of the immune thrombocytopenia (ITP) treatment landscape over the past two decades, there remain many areas of high unmet need. Therefore, a number of investigational and repurposed agents are currently undergoing clinical development in ITP. In a departure from historical trials, which largely focused on the indefinite treatment of persistent or chronic ITP, ongoing trials run the gamut of disease phases, and include novel agents being evaluated in early phases of the disease to attempt to modify the disease course. Many agents in development target disease pathophysiologic mechanisms not previously targeted by agents in current use, including platelet autoantibody recycling, B-cell maturation and differentiation, long-lived plasma cells, and the complement system, among others. These agents represent promising treatment options for patients with otherwise refractory disease or who are intolerant of currently available therapies. Additionally, with our increasing understanding of the diverse immune mechanisms at play in ITP, the expansion of the therapeutic armamentarium to include agents targeting diverse pathophysiologic mechanisms may allow a more personalized therapeutic selection in the future. This manuscript provides an up-to-date, in-depth overview of recently completed and ongoing clinical trials in ITP.

Could machine learning revolutionize how we treat immune thrombocytopenia?

The absence of reliable biomarkers in immune thrombocytopenia (ITP) complicates treatment choice, necessitating a trial-and-error approach. Machine learning (ML) holds promise for transforming ITP treatment by analysing complex data to identify predictive factors, as demonstrated by Xu etal.'s study which developed ML-based models to predict responses to corticosteroids, rituximab and thrombopoietin receptor agonists. However, these models require external validation before can be adopted in clinical practice. Commentary on: Xu etal. A novel scoring model for predicting efficacy and guiding individualised treatment in immune thrombocytopenia. Br J Haematol 2024; 205:1108-1120.

Navigating Primary Immune Thrombocytopenia During Pregnancy With Management Strategies and Considerations: A Comprehensive Review.

Primary immune thrombocytopenia (ITP) is an autoimmune disorder characterized by a reduction in platelet count due to autoantibody-mediated platelet destruction. ITP presents unique challenges during pregnancy, affecting both maternal and fetal health. This comprehensive review explores the pathophysiology, diagnosis, and management strategies of ITP in pregnant women, emphasizing the importance of individualized care. The incidence of ITP in pregnancy is significant, with potential complications including maternal hemorrhage and neonatal thrombocytopenia. Effective management is crucial to minimize these risks and ensure optimal outcomes. First-line treatments typically include corticosteroids and intravenous immunoglobulin (IVIG), with second-line options such as immunosuppressive agents and thrombopoietin receptor agonists. This review highlights the significance of multidisciplinary care and the need for careful monitoring and adjustment of treatment plans based on the severity of thrombocytopenia and the pregnancy stage. This review aims to enhance clinical decision-making and improve maternal and fetal outcomes in pregnancies complicated by ITP by providing a detailed analysis of current practices and emerging therapies.

Exploring the Structural Landscape for a Thrombopoietin Receptor Agonist Avatrombopag Maleate: An Innovative Trihydrate Forms with Improved Solubility Found

Exploring the Structural Landscape for a Thrombopoietin Receptor Agonist Avatrombopag Maleate: An Innovative Trihydrate Forms with Improved Solubility Found

Romiplostim in chemotherapy-induced thrombocytopenia: A review of the literature.

Chemotherapy-induced thrombocytopenia (CIT) is a common challenge of cancer therapy and can lead to chemotherapy dose reduction, delay, and/or discontinuation, affecting relative dose intensity, and possibly adversely impacting cancer care. Besides changing anticancer regimens, standard management of CIT has been limited to platelet transfusions and supportive care. Use of the thrombopoietin receptor agonist romiplostim, already approved for use in immune thrombocytopenia, has shown promising signs of efficacy in CIT. In a phase 2 prospective randomized study of solid tumor patients with platelet counts <100 × 109/L for ≥4 weeks due to CIT, weekly romiplostim corrected the platelet count to >100 × 109/L in 93% (14/15) of patients within 3 weeks versus 12.5% (1/8) of untreated patients (p < 0.001). Including patients treated with romiplostim in an additional single-arm cohort, 85% (44/52) of all romiplostim-treated patients responded with platelet count correction within 3 weeks. Several retrospective studies of CIT have also shown responses to weekly romiplostim, with the largest study finding that poor response to romiplostim was predicted by tumor invasion of the bone marrow (odds ratio, 0.029; 95% CI: 0.0046-0.18; p < 0.001), prior pelvic irradiation (odds ratio, 0.078; 95% CI: 0.0062-0.98; p = 0.048), and prior temozolomide treatment (odds ratio 0.24; 95% CI: 0.061-0.96; p = 0.043). Elsewhere, lower baseline TPO levels were predictive of romiplostim response (p = 0.036). No new safety signals have emerged from romiplostim CIT studies. Recent treatment guidelines, including those from the National Comprehensive Cancer Network, now support consideration of romiplostim use in CIT. Data are expected from two ongoing phase 3 romiplostim CIT trials.

Avatrombopag as alternative therapy for severe aplastic anemia patients who are intolerant or unresponsive to eltrombopag.

Eltrombopag (EPAG), a thrombopoietin receptor agonist, was approved for the treatment of severe aplastic anemia (SAA) combined with immunosuppressive therapy (IST). However, EPAG contains a typical biphenyl structure, which causes liver function damage. Twenty patients with SAA who were intolerant or refractory to EPAG were enrolled in a multicenter prospective registry of the Chinese Eastern Collaboration Group of Anemia (ChiCTR2100045895) from October 2020 to June 2023. Eight patients who were ineffective to EPAG, six with kidney impairment, and nine with abnormal liver function (two with concomitant liver and kidney impairment) were converted to avatrombopag (AVA) therapy with the median duration of AVA treatment was 6 (3-24) months. 17 cases (85%) achieved trilineage hematological response (HR): complete remission (CR) in 3 cases (15%), good partial remission (GPR) in 4 cases (20%), partial remission (PR) in 10 cases (50%), and no response (NR) in 3 cases (15%). The median time to response was 1.7 (0.5-6.9) months, with 16 cases (94%) achieving response within six months and 17 cases (100%) within 12 months. 9 cases (50%) achieved transfusion independence. AVA converted treatment was associated with higher neutrophil counts (0.8×109/L vs 2.2×109/L, p=0.0003), platelet counts (11×109/L vs 39×109/L, p=0.0008), hemoglobin count (59g/L vs 98g/L, p=0.0002), red cell count (1.06×1012/L vs 2.97×1012/L, p=0.001), and absolute reticulocyte count (31.99 ×109/L vs 67.05×109/L p=0.0004) were all significantly elevated compared with the pre-treatment level. After the conversion to AVA therapy, liver and kidney function indexes were maintained within the normal range, no AVA related grade 2 or higher adverse events occurred, and no thrombotic events occurred. The conversion to AVA was an optimal choice for patients with SAA who were EPAG intolerant or refractory. http://www.chictr.org.cn/showproj.html?proj=125480, identifier ChiCTR2100045895.

Retrospective Evaluation of Survival and Prognostic Factors in Immune Thrombocytopenia: A Single-Center and Cross-Sectional Study.

Background and Objectives: Immune thrombocytopenia (ITP) is an autoimmune disease characterized by the autoantibody-mediated destruction of platelets. The treatment of ITP aims to maintain a sufficient platelet count to prevent bleeding. First-line treatment options include corticosteroids and intravenous immunoglobulin (IVIg), while second-line treatments include splenectomy, rituximab and other immunosuppressive agents, and thrombopoietin (TPO) receptor agonists. This study aims to discuss the treatment methods and results from 100 patients with ITP at the Muğla Training and Research Hospital through a pharmacological approach. Materials and Methods: Demographic characteristics, clinical findings, bone marrow aspiration and biopsy results, and treatments and treatment responses at the time of diagnosis of the 100 patients with ITP who were treated and followed up in the period 2015-2023 were evaluated retrospectively. Results: In the third month after treatment, the overall response percentage was 100% in patients who received steroids only and 88% in patients who received IVIg treatment alone or in combination with steroids (p > 0.05). The most preferred second-line treatments were splenectomy (41%), eltrombopag (26%), and rituximab (10%). Bone marrow biopsy was performed in 54% of patients, where 35.1% showed increased megakaryocytes, 44.4% adequate megakaryocytes, and 14.8% decreased megakaryocytes. It is noted that eltrombopag and rituximab, in particular, yield higher complete remission rates than immunosuppressive drugs. Conclusions: Considering the side effects of immunosuppressive medications, IVIg, splenectomy, and steroid therapy, the use of new agents such as eltrombopag, which are easily tolerated and have a lower risk of side effects, is expected to increase.

Bioequivalence and Food Effect Assessment of Eltrombopag Olamine Tablets in Healthy Chinese Subjects: An Open, Randomized, Single-Dose, and Two-Period Crossover Study.

Eltrombopag, a nonpeptide thrombopoietin receptor agonist, is primarily used for treating immune thrombocytopenic purpura. The aim of this study was to investigate the pharmacokinetic profile and food-drug interaction of test and reference eltrombopag olamine tablets among healthy Chinese volunteers. An open, randomized, single-dose, 2-period crossover design was employed, involving fasting and fed conditions with a 10-day washout period. Ninety-six healthy volunteers received a single oral dose of 25mg of the 2 eltrombopag formulations, with 48 participants in each group: fasting volunteers and those consuming a high-fat, low-calcium meal. Plasma eltrombopag concentrations were analyzed using liquid chromatography-tandem mass spectrometry, and pharmacokinetic parameters were derived from the concentration-time profiles. The geometric mean ratios, with 90% confidence intervals, for the maximum plasma concentration, area under the concentration-time curve from time 0 to the last measurable concentration, and area under the concentration-time curve from time 0 to infinity fell within the bioequivalence acceptance criteria (80%-125%) under both fasting and fed conditions, indicating bioequivalence between the test and reference formulations. Administration of eltrombopag with a high-fat, low-calcium diet reduced the net systemic exposure by approximately 40%. Adverse events were recorded, and no serious adverse events were observed in either fasting or fed conditions. In conclusion, eltrombopag is well tolerated and exhibits a favorable safety profile in the Chinese population. The achievement of bioequivalence under fasting and fed conditions supports the demonstration of biosimilarity between the test and reference formulations.