Eltrombopag Initiation Research Articles

Use of Eltrombopag for Post-CAR T Cytopenias: A Multi-Institutional Experience

Background: Cytopenias following chimeric antigen receptor T (CAR T) cell therapy are common and can be profound and/or prolonged, leading to increased morbidity and mortality. Supportive care is the mainstay of management but strategies to reduce the duration and severity of cytopenias have yet to be optimized. One such strategy extrapolated from experience in aplastic anemia is the use of thrombopoietin (TPO) receptor agonists, like eltrombopag. Eltrombopag has been used off-label for several years for this indication, however, limited data exists regarding the safety and efficacy of its use after CAR T-cell therapy. Methods: Patients ≥ 18 years of age treated with CAR T-cell therapy for either lymphoma or myeloma at two academic medical centers between January 2018 and January 2023 were included in a retrospective analysis. Use of eltrombopag was initiated at the KUMC for patients who had received CAR T and subsequently had persistent cytopenias at day +30 as evidenced by at least one of four criteria: grade 3 or 4 leukopenia, grade 4 thrombocytopenia, growth factor dependency, or platelet transfusion dependency. Use of eltrombopag was initiated at the MUSC for patients who had received CAR T and had grade 4 thrombocytopenia at day +21 and beyond post-CAR T infusion. Baseline patient and disease characteristics as well as variables describing safety and efficacy of eltrombopag for the treatment of persistent high-grade leukopenia and/or thrombocytopenia beyond day +21 post CAR T infusion were collected and summarized using descriptive statistics. Results: A total of 185 patients were included in this analysis. Of these, 163 (88%) experienced thrombocytopenia or leukopenia at day +30 post-CAR T infusion. A total of 42 patients met institutional criteria for eltrombopag treatment and initiated therapy. Median time to initiation of eltrombopag was 33 days (range 28-50) from infusion, with no significant differences between the two institutions (30 days at KUMC vs 36 days at MUSC, p=0.19). Median duration for the use of eltrombopag was 63 days (range 32-172) and KUMC used eltrombopag for a longer duration than MUSC (108 days vs 32 days, p=0.03). There were no statistically significant differences in bleeding events in the eltrombopag vs non-eltrombopag groups, p=0.053, and no reported cases of deep vein thrombosis or pulmonary embolism (DVT/PE) after initiating eltrombopag. Patients on eltrombopag were more likely to have infections (24 (57%) vs 42 (35%), p<0.01) and admission to intensive care unit (16 (38%) vs 20 (17%), p<0.01) when compared to the non-eltrombopag group. At day +30, 74 (45%) patients in the entire study population had grade 3 or higher leukopenia or thrombocytopenia, with 39 (93%) and 25 (29%) patients in the eltrombopag and non-eltrombopag groups with grade 3 or higher cytopenias, respectively ( p<0.001). By day +90, only 18 (35%) patients in the evaluable population had grade 3 or higher leukopenia or thrombocytopenia, with 12 (50%) and 6 (22%) patients in the eltrombopag and non-eltrombopag groups with grade 3 or higher cytopenias, respectively ( p=0.046). By day +180, all but ten patients in the evaluable population had not recovered to less than a grade 3 cytopenia with no significant difference in cytopenias between the two groups. With a median follow up of 12 months (range 1-34) for the entire patient population, median PFS was lower for the eltrombopag group (13 months) compared to the non-eltrombopag group (16 months, p=0.02). When stratified by disease, this association was observed only for the lymphoma patients, with a median PFS of 8.5 months in the eltrombopag group compared to a median PFS of 17 months in the non-eltrombopag group, p=0.01 (Table 1). Similarly, for the entire patient population, median OS was lower for the eltrombopag group (14 months) compared to the non-eltrombopag group (18 months, p=0.01). When stratified by disease, this association was observed only for the lymphoma patients, with a median OS of 14 months in the eltrombopag group compared to 18 months in the non-eltrombopag group ( p<0.01). Conclusions: In this first of its kind real-world experience, use of eltrombopag for post-CAR T leukopenia and thrombocytopenia was considered effective in recovery of counts and prevention of bleeding in a high-risk patient population. The use of eltrombopag for post-CAR T cytopenias was considered safe without any significant toxicities of thrombosis or myelodysplasia.

Long-Term Eltrombopag in Children with Chronic Immune Thrombocytopenia: A Single-Center Extended Real-Life Observational Study in China

Background: We have previously confirmed the efficacy and safety of eltrombopag (ELT) in children with chronic immune thrombocytopenia (cITP). However, there is still a lack of results on long-term ELT therapy. Here, we report the long-term follow-up results ( between September 2018 and June 2023 ) on our previous study. Methods: This is a single-center real-life observational study that collected data from patients who previously enrolled in our children cITP study and had a follow-up period of more than 3 years by June 2023. Results: A total of 65 patients (28 males) were enrolled with a median age at ELT initiation of 6.34 (range 1.65, 14.13) years and a 47.07 (36.00, 57.00) months follow-up time with a 40.36 (10.53, 56.83) months of ELT therapy at the analysis time point. In total, 29.23% (19/65) (of) patients discontinued ELT because of a stable response, and 18.46% (12/65) patients switched to another platelet-enhancing therapy due to loss of response to therapy after 19.13 (14.53, 26.37) months. Among the 19 patients who discontinued ELT because of a stable response, 24.62% (16/65) children achieved 12 m of off ELT treatment(SRoT), the last recorded platelet count ranged from 56-166×10 9/L (median value 107×10 9/L), and 4.62% (3/65) patients relapsed at the 5th, 6th, and 9th months after discontinuation, respectively. Of the 12 patients who lost response to ELT after 19.13 (14.53, 26.37) months of therapy, four switched to avatrombopag, three to hetrombopag, two to Chinse traditional medicine, one had splenectomy and two received additional prednisolone acetate. Thirty-four patients maintained a sustained response while continuing on ELT treatment but with tapering doses. No significant adverse events were reported. In the first 12 months of ELT, there was a higher rate of PLT ≥ 100×10 9/L in SRoT patients than in tapering patients (62.50% [10/16] vs. 5.88% [2/34]) and a higher rate of PLT 70-100×10 9/L (31.25% [5/16] vs. 27.78% [10/36]) ( P=0.01). Conclusion: We report more than 3 years long-term clinical data on cITP children taking ELT. We show that 24.62% of the children who had a stable response to ELT achieved 12 m of SRoT. The treatment response of children in the first 12 months after the initiation of treatment may be a predictive factor for successful discontinuation. These data highlight no new safety concerns regarding the long-term use of ELT in children with cITP.

Association of Clinical Response of ITP Patients to Eltrombopag with the Regulation of Platelet Binding to Lymphocytes

Introduction Primary immune thrombocytopenia (ITP) is caused by the destruction of platelets (PLT) and megakaryocytes by autoantibodies, cellular cytotoxicity, or/and impairment in PLT production. Thrombopoietin-receptor agonists (TPO-RA) are a commonly used therapy in ITP that activate JAK/STAT pathways, stimulating megakaryocyte growth and PLT production. TPO-RAs, which include eltrombopag (EPAG), are effective in restoring PLT count in 70-80% of cases with chronic ITP. Recently, it has been observed that PLTs have an immunoregulatory role and their binding to lymphocytes and monocytes can modulate leukocyte inflammatory profile. Our aim was to determine the percentage of lymphocytes with bound PLTs before and after EPAG treatment, analyzing factors associated with this binding and with response. Methods For this purpose, peripheral whole blood was collected from 43 ITP patients relapsed/refractory to corticosteroids (at baseline and 2, 4, 12, and 18 w after the initiation of EPAG) and 15 healthy donors (HD). The percentage of T CD4+, T CD8+, and B lymphocytes with bound PLTs (CD41a+) were analyzed by flow cytometry and plasma levels of cytokines (IFN-γ, TNF-α, IL-10 and IL-17) by ELISA. Results In comparison with HD, the absolute number of PLTs was lower and the percentage of free activated PLTs was higher in ITP patients at baseline. Additionally, the percentage of T and B lymphocytes with bound PLTs in ITP patients was lower than in HD. After 2w of EPAG treatment, the percentages of T and B lymphocytes with bound PLTs were normalized and IFN-g levels were reduced. However, no significant changes were observed in the percentage of free-activated PLTs and in the percentage of T and B lymphocytes with bound activated PLTs. The percentages of T and B lymphocytes with bound PLTs were higher in ITP patients that reached complete response (>100 x 109 PLT/L without bleeding) compared with partial response (30-100 x 109 PLT/L) and non-response (<30x 109 PLT/L) patients in each time point of the study after EPAG treatment (Figure 1). Conclusions Our results suggest that the increase of PLTs after EPAG treatment is not only mediated through the platelet production stimulation, but also through the increase of PLT binding to lymphocytes which may influence the inflammatory profile of ITP patients. This newly mechanism of action could explain the persistent response of ITP patients after EPAG treatment. Figure 1View largeDownload PPTFigure 1View largeDownload PPT Close modal

Eltrombopag Combining Rituximab Versus Eltrombopag for Treatment of Adult Immune Thrombocytopenia: A Single Center, Retrospective Cohort Study

Introduction: Immune thrombocytopenia (ITP) is the most common hematological acquired hemorrhagic disease characterized by antibody-mediated platelet destruction and/or megakaryocyte maturation disorders. Eltrombopag and other thrombopoietin receptor agonists can rapidly increase the platelet count of patients with ITP by promoting megakaryocyte maturation and immune regulation, and effectively reducing the risk of bleeding. However, platelet levels often fall to baseline levels in the short term after drug withdrawal. Rituximab prevents the excessive destruction of platelets in patients by eliminating the autoantibody-secreting B cells. Although it takes a long time to act, some patients can achieve long-term remission. To explore the feasibility of the combination of two drugs with different mechanisms, we retrospectively analyzed the efficacy and safety of patients treated with eltrombopag combined with rituximab or eltrombopag monotherapy in our center. Methods: Collected the clinical data of patients with immune thrombocytopenia admitted to our center from October 2017 to December 2021. Patients included in the analysis were required to meet the following inclusion and exclusion criteria: 1) aged more than 18 years; 2) without acute infection, liver or kidney injury; 3) without high-risk factors for thrombosis; 4) not accompanied by severe immunodeficiency disease. All patients accepted eltrombopag or a combination regimen with rituximab. The initial dose of eltrombopag was 50mg/75mg daily, and the combination group received an intravenous infusion of rituximab (375mg/m2, once) within 1 month of the initiation of eltrombopag. During follow-up, the dose of eltrombopag was adjusted according to the patient's platelet count. The primary endpoints were complete response (CR), response (R), and overall response (OR) after 8 weeks, 12 weeks, and 24 weeks of treatment. Platelet counts should be confirmed on two separate occasions at least 7 days apart when defining responses (CR: platelet count ≥ 100×109/L and absence of bleeding; R: platelet count ≥ 50 × 109/L and at least a doubling of baseline and absence of bleeding; OR: platelet count ≥30 × 109/L or ≥2-fold increase of the baseline platelet count or bleeding). Secondary endpoints included sustain response off therapy (SRoT), duration of response, and adverse events (AEs). Results: 152 patients were enrolled in our study, 80 patients received eltrombopag plus rituximab and 72 patients received eltrombopag monotherapy. 6 patients in the combination group, and 9 patients in the monotherapy group did not receive the allocated intervention (5 and 7 for adding other treatments, 1 and 2 due to the diagnosis change). 5 and 10 lost to follow-up in combination and monotherapy groups, respectively. Eventually, 69 patients in the eltrombopag plus rituximab group and 53 patients in the eltrombopag group analyzed the efficacy and safety. The median follow-up time was 46 weeks (4-177w) vs 30 weeks (4-190w), respectively. Results showed that after 12 weeks and 24 weeks of treatment, the percentage of patients who reached R in the combination group was higher than in the monotherapy group (72.3% vs 54.0%, P=0.042; 70.0% vs 50.0%, P=0.041). And the OR after 12 weeks of treatment was also higher in the eltrombopag plus rituximab group (80.0% vs 64.0%, P=0.055). 17 patients (24.6%) in the combination group, and 5 patients (9.4%) in monotherapy can discontinue the eltrombopag successfully and maintain the platelet count ≥30 × 109/L for more than 2 months (P=0.03). There was no significant difference in the incidence of abnormal liver function and infection between the two groups (P>0.05). 11 patients (15.9%) reported medicated alopecia and 1 patient developed deep vein thrombosis of the lower extremity. Conclusion: The combination of eltrombopag and rituximab was safe and active in patients with immune thrombocytopenia, showing a sustained response, some patients can be successfully discontinued. This regimen provides a new possibility of drug combination therapy with different mechanisms for the long-term efficacy of ITP. Figure 1View largeDownload PPTFigure 1View largeDownload PPT Close modal

Efficacy and Safety of Eltrombopag with or without Immunosuppressant in Patients with Relapsed/Refractory Acquired Aplastic Anemia: A Real-World Experience

Background: Eltrombopag (EPAG) with or without immunosuppressant (IST) has been applied in acquired aplastic anemia (AA), yet data of EPAG+IST in relapsed/refractory AA was limited, and no study has compared efficacy and safety between EPAG+IST and EPAG monotherapy in relapsed/refractory AA patients.Aims: To evaluate and compare the efficacy and safety between EPAG+IST and EPAG monotherapy in relapsed/refractory AA patients in a real-world setting.Methods: Data from patients diagnosed as acquired AA in our center were retrospectively collected. All the enrolled patients were refractory/relapsed to the standard IST for at least 6 months before EPAG. All patients had been treated with EPAG, which was started at 25 mg/day and increased every 2 weeks to a maximum of 150 mg/day until a best response was achieved. Meanwhile, some patients were treated with cyclosporin A (CsA) or tacrolimus (FK506) at the same time. EPAG had to be prescribed for at least 6 months before evaluation. Complete response (CR), overall response (OR) and relapse rate, as well as adverse events and factors which could affect efficacy were analyzed.Results: Totally 99 patients (83 non-severe AA (NSAA) and 16 SAA) were included in the study. The median age at EPAG initiation was 46 (13-88) years old, the median time of EPAG treatment was 11 (6-41) months and the median time of follow-up was 18 (6-41) months. 72 patients were treated with EPAG+IST, including 41 (56.9%) treated with EPAG+FK506 and 31 (43.1%) treated with EPAG+CsA. 27 patients were treated with EPAG alone. No significant difference was found between EPAG+IST group and EPAG group in patient baseline characteristics like age, male proportion, NSAA proportion, presence of PNH clone, proportion of previous ATG+CsA / CsA treatment, previous IST duration and dosage. With compatible follow-up time, EPAG exposure duration and dosage, there was no significant difference in OR/CR rate at 3 rd/6 th/12 th month between patients who was treated with EPAG+FK506 and EPAG+CsA. Under similar compatible baseline conditions, the OR rate was 33.3% vs 22.2% (P=0.284) at 3 rd month, 61.1% vs 37.0% (P=0.032) at 6 th month, and 67.2% vs 42.1% (P=0.051) at 12 th month for patients treated with EPAG+IST and EPAG alone, respectively, but no significant difference was found in time to response (3 (1-12) vs 3 (1-7) months, P=0.679) or CR rate at 3 rd/6 th/12 th month (6.9%/12.5%/20.7% vs 3.7%/7.4%/5.3%, P>0.05) between the two groups. Relapse occurred at 6 th to 12 th month of EPAG treatment, and the relapse rate at 12 th month was 9.8% and 27.3% (P=0.154) for patients treated with EPAG+IST and EPAG alone, respectively. For patients treated with EPAG+IST, responders had a significantly higher baseline reticulocyte count (60.25 (11.5-230.5)×10 9/L vs 16.7 (6.6-56.6)×10 9/L, P=0.040) compared with non-responders. No predictive factors for the overall response were found for patients treated with EPAG alone. Adverse events which led to dosage regulation were gastrointestinal disorders (2.8% vs 3.7%, P=1.000), elevated creatinine (2.8% vs 0, P=0.599), elevated ALT (1.4% vs 0, P=1.000) and arthralgia (0 vs 3.7%, P=0.280) for patients with EPAG+IST and EPAG, respectively. No deaths were found in either group, while the clone evolution rate was 2.8% and 3.7% (P=1.000) in EPAG+IST and EPAG monotherapy group, respectively.Conclusion: EPAG+IST had higher OR rate than EPAG monotherapy with similar side effects for patients with relapsed/refractory acquired AA. Those with higher baseline reticulocyte count were more likely to respond to EPAG+IST.Key words: relapsed/refractory, aplastic anemia, eltrombopag, immunosuppressant, efficacy DisclosuresNo relevant conflicts of interest to declare. OffLabel Disclosure:In the presented study, eltrombopag was prescribed in relapsed/refractory aplastic anemia patients.

Eltrombopag treatment of patients with secondary immune thrombocytopenia: retrospective EHR analysis

Immune thrombocytopenia (ITP) may occur in isolation (primary) or in association with a predisposing condition (secondary ITP [sITP]). Eltrombopag is a well-studied treatment for primary ITP, but evidence is scarce for sITP. We evaluated real-world use of eltrombopag for sITP using electronic health records. Eligible patients had diagnoses of ITP and a qualifying predisposing condition, and eltrombopag treatment. We described patient characteristics, treatment patterns, platelet counts, and thrombotic and bleeding events. We identified 242 eligible patients; the most common predisposing conditions were hepatitis C and systemic lupus erythematosus. Average duration of eltrombopag treatment was 6.1 months. Most (81.4%) patients achieved a platelet count ≥ 30,000/µL at a mean of 0.70 months, 70.2% reached ≥ 50,000/µL at a mean of 0.95 months, and 47.1% achieved a complete response of > 100,000/µL at a mean of 1.43 months after eltrombopag initiation. At eltrombopag discontinuation, 105 patients (43%) experienced a treatment-free period for a mean 3.3 months. Bleeding events occurred with similar frequency before and during eltrombopag treatment whereas thrombotic events were less frequent during eltrombopag treatment. Our results suggest similar rates of platelet response with eltrombopag in patients with sITP as compared with primary ITP. In addition, a treatment-free period is possible for a substantial minority of patients.

Evaluation of Treatment Patterns Among Patients with Newly Diagnosed, Persistent, and Chronic Immune Thrombocytopenia (ITP) Treated with Eltrombopag in Real World Setting in the US

BACKGROUND: The thrombopoietin receptor agonist (TPO-RA) eltrombopag was approved for the treatment of chronic immune thrombocytopenia (cITP), >12 months after initial ITP diagnosis. The registration trials however included patients with ITP duration >6 months. Moreover, with increasing familiarity and confidence with the use of TPO-RAs in ITP, the use of these agents in real world has not been restricted to cITP.OBJECTIVE: The objective of this study was to describe treatment characteristics of eltrombopag use among adult patients diagnosed with ITP initiating treatment ≤6, 7-12, and >12 months after their initial ITP diagnosis in the real-word setting.METHODS: A retrospective cohort study was conducted using MarketScan® - Commercial and Medicare Supplemental Database, and PharmetricsPlusTM Adjudicated Claims Database. Adult patients (≥18 years) with ≥2 non-diagnostic outpatient claims separated by ≥30 days or ≥1 inpatient claim carrying a diagnosis code for ITP during Jul 1, 2010 - Jun 30, 2014 were eligible for inclusion. The index date was the date of the first ITP diagnosis. Patients were excluded if they had continuous enrollment in medical and pharmacy benefits for <24 months prior and <18 months following the index date, or had a medical claim for secondary thrombocytopenia during the pre-index period. Timing of eltrombopag initiation was calculated from the index date to the date of first eltrombopag claim. Patients were categorized into 1 of 3 cohorts, those initiating treatment ≤6, 7-12, or >12 months after index date. Treatment outcomes were assessed among a subset of patients regardless of follow-up period post the index ITP diagnosis but who had ≥6 months of continuous enrollment in medical and pharmacy benefits after initiating treatment with eltrombopag; treatment duration, medication possession ratio (MPR), time to treatment discontinuation and time to treatment restart were compared among patients initiating treatment ≤6, and 7-12 after ITP diagnosis to those initiating treatment >12 months after their index ITP diagnosis. MPR was calculated as the sum of the days' supply for all fills divided by the number of days between the first and last fill plus days' supply of the last fill. Outcomes compared between cohorts using t-tests and chi-square tests. RESULTS: A total of 7,068 patients - 3,264 patients in MarketScan and 3,804 in PharMetrics - were eligible for inclusion in the study; 117 (3.6%) and 139 (3.7%), respectively, received eltrombopag. More than half of patients in both MarketScan and PharMetrics initiated treatment ≤12 months after their index diagnosis (see Table 1). The average treatment durations were similar among patients initiating treatment ≤6 months (120.8±57.1; P =0.456) and 7-12 (110.5±59.5; P =0.991) months after index diagnosis compared to those initiating treatment >12 months after index diagnosis (110.3±64.7). The MPR was 0.9 in all 3 cohorts; 84.0%, 73.7% and 78.3% patients initiating treatment ≤6 months, 7-12 months and > 12months after index diagnosis, respectively were considered to be adherent based upon an MPR≥0.8. The proportion of patients who discontinued treatment were not statistically significant between cohorts (≤6 months: 53.3% [ P =0.816]; 7-12 months: 57.9% [ P =1.000]; >12 months 56.5%). Time to treatment discontinuation was statistically longer among patients initiating treatment ≤6 months compared to those initiating treatment >12 months after index diagnosis (63.7±37.3 days vs 39.5±26.4 days; P =0.035); however the difference between patients initiating treatment 7-12 and >12 months after index diagnosis (50.3±30.5 days vs 39.5±26.4 days; P =0.365) was not significant. Twelve percent (P =0.307), 26.3% (P =1.000) and 21.7% of patients initiating treatment ≤6 months, 7-12 and >12 months after index diagnosis restarted eltrombopag. The average time to treatment restart was approximately 50 days across all 3 cohorts. CONCLUSION: Although eltrombopag is currently approved for patients with chronic ITP, results of this study indicate that in real world setting physicians have been using it in patients with newly diagnosed and persistent ITP, with overall treatment patterns being very similar to those in patients with cITP. These data, supported by other real world studies underscore the clinical utility of eltrombopag in early-stage ITP and warrant further exploration in more robust prospective studies. [Display omitted] DisclosuresStafkey-Mailey:Xcenda: Employment. Roy:Novartis: Employment, Equity Ownership. Lokhandwala:Xcenda: Employment. Yuan:Xcenda: Employment. Landsman-Blumberg:Xcenda: Employment. Siddiqui:Novartis: Employment, Equity Ownership. Ghaznawi:Novartis: Employment, Equity Ownership.

Efficacy and cost analysis of eltrombopag in thrombocytopenia and poor graft function post allogeneic hematopoietic cell transplantation.

Eltrombopag has shown efficacy in the treatment of thrombocytopenia and poor graft function (PGF) after allogeneic hematopoietic cell transplantation (HCT) in retrospective observational studies, but is not approved for this indication. The cost of this drug is also a major concern in publicly funded health care systems. We collected data about patients who received eltrombopag for thrombocytopenia or PGF after HCT. Post-HCT thrombocytopenia, PGF, and eltrombopag response were defined as per previously published criteria. Primary outcome was treatment efficacy and secondary outcome was cost comparison between estimated treatment cost prior to and after initiation of eltrombopag. Seventeen patients (males 70.6%; median age = 58) received eltrombopag. Isolated thrombocytopenia was present in 11.8% (n = 2) patients while PGF was present in 88.2% (n = 15) of patients. After 8 weeks of treatment at the maximum dose of 150 mg orally daily, overall response rate (ORR) was seen in 76.5% (13/17) of patients: complete response (CR) in 10/13 patients and partial response (PR) in 3/13 patients. The use of eltrombopag was associated with an overall decrease in the total weekly care costs (5021 vs 2,524 CA$; P = 0.04). Thus, Eltrombopag is an efficacious and possibly cost-effective therapy for thrombocytopenia and PGF after allogeneic HCT.

Use of eltrombopag for the treatment of poor graft function after hematopoietic stem cell transplantation in children.

The main objective of this study was to determine whether Eltrombopag, a synthetic thrombopoietin receptor agonist, could improve peripheral blood counts in the three hematopoietic lineages and achieve transfusion independence in children with poor graft function (PGF) after allogenic hematopoietic stem cell transplantation (HSCT). Retrospective study of patients under 18years who developed PGF post-HSCT in a large tertiary institution between January 2013 and March 2019. Out of 198 allogeneic HSCT, five patients met PGF criteria and were treated with eltrombopag. Median time from HSCT to eltrombopag initiation was 120days. The median starting dose was 50mg/day and the maximum dose reached was 75mg/day. Median treatment duration was 9months. Three patients achieved complete response and one partial response. The median dose among responders was 75mg/day and the median time to response 8weeks. Responses were sustained in three patients and two required a booster dose of CD34+ -selected cells from the original donor. None of the patients had to stop treatment due to adverse effects. The use of eltrombopag in children with PGF achieved responses in 80% of cases and demonstrated to be an effective and safe therapeutic option in pediatric patients with PGF.

Eltrombopag for the treatment of refractory thrombocytopenia associated with connective tissue disease

To assess the efficacy and safety of eltrombopag in connective tissue disease (CTD)-immune thrombocytopenia (ITP), we conducted this single-center retrospective observational study, including patients with refractory CTD-ITP who were treated with eltrombopag between January 2018 and August 2019. The characteristics of patients at baseline, and the efficacy and safety of the drug were analyzed. The predictors for a response were analyzed using a univariate analysis such as Chi-square or nonparametric test and a multiple correspondence analysis (MCA) method. A total of 15 patients with refractory CTD-ITP were included in the study. Their median age at the time of inclusion was 40.6 years. The median platelet count at initiation of eltrombopag was 11.53 × 109/L. The median remission time was 3.42 weeks. The complete remission (CR) and overall response rate decreased with time. The factors that associated with response to eltrombopag in patients with CTD-ITP were protopathy, WBC counts, levels of hemoglobin, and characteristics of bone marrow findings in univariate analysis. In addition, MCA indicated that a poor response to eltrombopag in patients with refractory CTD-ITP was closely associated with a protopathy with SS, medium to severe degree of anemia, leukopenia, and bone marrow aspiration showing aplastic anemia, an absence of megakaryocytes or macrophage activation syndrome (MAS). In conclusion, eltrombopag was effective and well-tolerated in patients with CTD-associated thrombocytopenia. Some factors should be considered in the use of eltrombopag, including the protopathy, blood test, and bone marrow histology.

The association of lymphocyte phenotypes and outcomes after discontinuing eltrombopag in immune thrombocytopenia.

Eltrombopag is a highly effective treatment for immune thrombocytopenia (ITP). Cases of durable remission after the discontinuation of eltrombopag in adult ITP have recently been reported; however, the frequency and mechanisms responsible for this phenomenon remain unknown. In the present study, we examined the phenotypes of lymphocytes in ITP to clarify whether they predict outcomes after the discontinuation of eltrombopag. We analysed 56 adult ITP patients treated with eltrombopag at our hospital between January 2008 and January 2020. Patients' characteristics at the initiation and discontinuation of eltrombopag, the prognostic significance of lymphocytes and other factors were evaluated. A total of 38 patients showed complete response (CR). Eltrombopag was discontinued in 28 of 38 patients who achieved CR. Among the 28 patients, 12 (42.8%) had an immediate relapse after discontinuing eltrombopag and 16 (57.2%) showed sustained response without additional ITP therapy, despite discontinuing eltrombopag, with a median follow-up of 42months. No significant differences were observed in platelets, the median duration of eltrombopag, the absolute number of T, B and NK cells at the initiation of eltrombopag between patients who sustained response and those who relapsed after discontinuing eltrombopag. However, the number of B and NK cells at the discontinuation of eltrombopag was higher in patients who sustained response than in those who relapsed (P=.022 and P=.012 respectively). The present results indicate that the absolute number of B (≥0.20×109 /L) and NK (≥0.30×109 /L) cells at the discontinuation of eltrombopag contributes to the prediction of outcomes.

Eltrombopag for Immune Thrombocytopenia in Adult Patients in the Real-World in France. Final Results of the Elextra Study

Introduction:Eltrombopag has been available in Europe for the treatment of chronic primary immune thrombocytopenia (ITP) since 2010. Since 2019, it has been indicated in patients with primary ITP, lasting 6 months or longer from diagnosis and who are refractory to other treatments, aged 1 year and above. However, data are lacking regarding the use, the efficacy and the safety of eltrombopag in clinical practice in Europe. The ELEXTRA study aimed to assess these questions in France. The intermediate results were presented at the 2019 ASH Annual Meeting. We present here the final results of the ELEXTRA study. Methods:Population source was the CARMEN-France registry. The CARMEN (Cytopénies Auto-immunes : Registre Midi-PyréneEN) registry is aimed at the prospective follow-up of all incident ITP adults in the French Midi-Pyrénées region (South-West of France, 3 million inhabitants) since June 2013. Each investigator follows all adult patients (aged ≥18 years) newly diagnosed with ITP in routine visits or hospital stays, and detailed information on patients' characteristics and management of ITP are prospectively recorded. This registry has been implemented in other French centers since 2016, taking the name of CARMEN-France. ITP was defined by platelet count &amp;lt;100 x 109/L and exclusion of other causes of thrombocytopenia. The study population consisted of all incident ITP adults included in the CARMEN-France registry from June 2013 to December 2019 who were exposed to eltrombopag during the disease course. We described the time from ITP diagnosis to first exposure to eltrombopag, and patients' characteristics. Efficacy was assessed in patients who had a platelet count &amp;lt;30 x 109/L at eltrombopag initiation. Overall response was defined by platelet count ≥30 x 109/L and complete response by platelet count ≥100 x 109/L. Adverse drug reactions (ADRs) that occurred during eltrombopag exposure were collected and assessed according to the World Health Organization causality assessment scale. All ADRs with causality score assessed at least as "possible"were described. Results:Out of 795 patients included in the registry, 156 (19.6%) had been exposed to eltrombopag for a median duration of 100 days (range: 1-1427). Mean age was 60.2 years (standard deviation: 20.9) and 79 (50.6%) were males; 60 (38.5%) had at least one comorbidity of the Charlson Comorbidity Index score; 89 (57.1%) had at least one cardiovascular risk factor (not including age and sex) and 9 (5.8%) a history of venous thrombosis. At ITP diagnosis, the median platelet count was 8 x 109/L (range: 1-88 x 109/L) and 118 (75.6%) patients had bleeding. Median time from ITP onset to first exposure to eltrombopag was 3.3 months (range: 0.1-82.2): 74 (47.4%) patients were exposed before 3 months of ITP duration, 21 (13.5%) between 3 and 6 months and 61 (39.1%) after 6 months. Exposures to ITP treatments before eltrombopag initiation were: corticosteroids in 150 (96.2%) patients, intravenous immunoglobulin (IVIg) in 106 (67.9%), dapsone in 28 (17.9%), rituximab in 26 (16.7%), romiplostim in 12 (7.7%), hydroxychloroquine in 14 (9.0%), danazol in 8 (5.1%), vinblastine in 5 (3.2%), azathioprine in 2 (1.3%), ciclosporin in 1 (0.6%) and splenectomy in none. Eltrombopag was used as second-line agent in 52 (33.3%) patients and third-line in 56 (35.9%). Among the 156 patients, 75 (48.1%) had a platelet count &amp;lt;30 x 109/L at eltrombopag initiation; among them, 65 (86.7%) achieved overall response and 53 (70.7%) complete response at any time during exposure to eltrombopag. Among the 65 patients who achieved overall response, 58 (89.2%) had a concomitant exposure to another ITP treatment at eltrombopag initiation (including steroids, n=42; IVIg during the past month, n=44; rituximab in the past 6 months, n=11). Overall, 47 ADRs were reported: the most frequent were: thrombocytosis (n=10), thrombosis (n=8: 6 pulmonary embolism, 1 deep and 1 superficial vein thrombosis), rash (n=4), hepatitis (n=3),and headache (n=3). Conclusion:In French real-world practice, eltrombopag is used early in the ITP course. Efficacy is similar to that observed in clinical trials. The safety profile identified in clinical trials is also confirmed. Disclosures Moulis: Grifols: Research Funding; Amgen: Other: meeting attendance grant; Novartis SAS: Membership on an entity's Board of Directors or advisory committees, Other: meeting attendance grant, Research Funding. OffLabel Disclosure: Real-World use of eltrombopag in immune thrombocytopenia

Efficacy and Cost Analysis of Eltrombopag in Thrombocytopenia and Poor Graft Function Post Allogeneic Hematopoietic Cell Transplantation in a Canadian Centre - a Prospective Observational Study

Background - Thrombocytopenia and poor graft function(PGF) after allogeneic hematopoietic cell transplantation (HCT) may be defined as incomplete count recovery or late cytopenias not due to relapse. There is lack of evidence based treatment for PGF with commonly used modalities being supportive care, second transplants and CD34+ selected stem cell boosts. Eltrombopag, a thrombopoietin receptor agonist, stimulates proliferation and differentiation of hematopoietic stem cells (HSC). It has shown efficacy for PGF in observational studies, but is not approved for this indication. Cost of this drug is a major concern in state sponsored health care systems. Methods - We retrospectively and prospectively collected data about patients who received Eltrombopag for thrombocytopenia and poor graft function after HCT. Post HCT thrombocytopenia was defined as persistent platelet count ≤ 20 x 10^9/l or transfusion dependence. PGF was defined if there was persistence of 2/3 cytopenias: thrombocytopenia, neutropenia (≤ 1.5 x 10^9/l) and/or haemoglobin ≤ 70g/l or transfusion dependence after day 28 of HSCT with complete donor chimerism and no evidence of relapse. Transplant characteristics, post-transplant complications and transfusion history was noted. In treated patients, Eltrombopag was initiated at 50 or 100mg daily and increased every 2 weeks to maximum of 150mg daily based on response. Response criteria: Complete Response (CR) - sustained platelet count ≥ 50 x 10^9/l, haemoglobin≥ 100g/L and ANC ≥ 1.5x10^9/L without transfusions; Partial response (PR) - platelet count 20-50 x 10^9/l or Hb 7-10g/L or ANC 0.5-1.5 x 10^9/l. Cost of transfusions were calculated from estimates of Canadian Blood Services and of hospital admissions were based on local hospital estimates. Cost estimation prior to Eltrombopag was calculated by the cost of supportive care from diagnosis of PGF or thrombocytopenia to initiation of Eltrombopag. Cost estimation post Eltrombopag was done by calculating the cost of drug intake + cost of supportive care (if any) after initiation of Eltrombopag. Primary outcomes were efficacy of drug and transfusion free survival; secondary outcomes were cost comparison between estimated cost prior to Eltrombopag and estimated cost after initiation of Eltrombopag. Results: 15 patients (males 66.67% (n=10); median age - 59 years) received Eltrombopag (Table 1). Indication of Eltrombopag was PGF in 86.7% (n=13) and isolated thrombocytopenia in 13.3% (n=2) patients. Response and cost analysis were limited to the 13 patients with at least 8 weeks follow-up after initiating Eltrombopag. After 8 weeks of Eltrombopag, Overall Response rate(ORR) was 76.9% (n=10; CR = 7; PR = 3). With median follow up of 6.2 months the drug was tapered or discontinued in 60% (n=6) patients showing response. All responders became transfusion independent within 8 weeks of maximum dose of Eltrombopag. The 3-month transfusion free survival after Eltrombopag was 70.7% (Figure 1A). Two out of three patients who did not respond to Eltrombopag died during the study period. The estimated median OS of non-responders vs responders = 12.4 months vs NR; p-0.063; Figure 1B). Eltrombopag was well tolerated with no incidence of serious adverse effects (Liver enzyme elevation, GI toxicity) to report. Rough estimates of cost analysis were done in patients who had response to Eltrombopag. These patients required median (IQR) of 15 (2-25) PRBC transfusions and 46 (32-96) pooled platelet transfusions with median 20 days of hospitalization due to cytopenia complications prior to 4 weeks after starting Eltrombopag. The median (IQR) duration of Eltrombopag exposure was 9.8 (6.3-25.6) weeks. The cost of supportive care before Eltrombopag was marginally higher than calculated total cost of Eltrombopag and subsequent supportive care treatment (Median cost 35311$ vs 33751 $CAD; p=0.9) (Figure 1C). The crude cost estimate of supportive care did not include cost estimates of human resources (including nursing), hospital visit time, time off work, and quality of life. Conclusion - Eltrombopag is a safe and efficacious therapy for thrombocytopenia and poor graft function after allogeneic HCT with response in 77% of patients. Preliminary cost analysis shows that Eltrombopag is cost neutral by reducing supportive care and hospitalization costs and may be especially relevant in countries where supply of safe and adequate blood products is a challenge. Figure Disclosures Lipton: Ariad: Consultancy, Research Funding; Takeda: Consultancy, Honoraria, Research Funding; Bristol-Myers Squibb: Honoraria; Novartis: Consultancy, Research Funding; BMS: Consultancy, Research Funding; Pfizer: Consultancy, Honoraria, Research Funding. Mattsson:ITB: Honoraria; Takeda: Membership on an entity's Board of Directors or advisory committees; Mallinkrodt: Honoraria; Jazz Pharmaceuticals: Honoraria; Gilead: Honoraria. OffLabel Disclosure: Eltrombopag is approved for ITP and Aplastic Anemia. It is currently not approved for thrombocyotpenia and poor graft function after Allogeneic Hematopoietic Cell Transplantation in Canada.

Healthcare resource use and direct costs in severe aplastic anemia (SAA) patients before and after treatment with eltrombopag

Purpose: This study evaluated healthcare resource utilization (HCRU), and direct costs among severe aplastic anemia (SAA) patients treated with eltrombopag (EPAG) using US claims data.Methods: This retrospective, real-world claims database study identified SAA patients aged ≥2 years treated with EPAG who initiated any SAA treatment between 1 July 2014 and 31 December 2017 (identification period) using the Truven MarketScan databases. A subset of 82 patients treated with EPAG during the identification period were evaluated for all-cause and SAA-related HCRU and direct costs as well as blood transfusion 1 month before EPAG initiation (baseline) and at Month 6 after EPAG initiation (follow-up period).Results: The average patient age was 50.8 (SD = 20.6) years old, predominantly female (n = 43, 52.4%), and had a mean CCI at baseline of 1.1 (SD = 1.7). Hospitalizations, and ER, office, and outpatient visits were significantly lower at Month 6 after EPAG initiation compared with 1 month before EPAG initiation (p < .05 for all four all-cause HCRU and SAA-related hospitalizations). An almost two-fold decrease in reliance on biweekly blood transfusions was observed: 1.0 at weeks 1–2 to 0.5 at Month 6 after EPAG initiation. Although prescription costs (mean [SD]) were significantly higher at Month 6 after EPAG initiation compared with 1 month before EPAG initiation (difference of $11,045 USD [SD = $18,801]), these increases were offset by savings in direct costs. Overall, a mean reduction in total all-cause costs of $29,391 USD [SD = $137,770] was reported at Month 6 after EPAG initiation due to substantial reductions in hospitalization ($40,060 USD [SD = $123,198]) and outpatient visits ($2,043 USD [SD = $25,264]).Conclusion: All-cause and SAA-related HCRU were reduced following EPAG treatment. Prescription costs were higher following treatment; however, these costs were generally offset by reductions in direct costs. These results provide real-world evidence around the role of EPAG in SAA treatment.

Eltrombopag for Immune Thrombocytopenia Adult Patients in the Real-Life Practice in France. Interim Results of the Elextra Study

Eltrombopag for Immune Thrombocytopenia Adult Patients in the Real-Life Practice in France. Interim Results of the Elextra Study

Real-World Effectiveness and Safety of Eltrombopag in Patients with Aplastic Anemia: A Chinese Nationwide Survey

Immunosuppressive therapy (IST) based on antithymoglobin (ATG) and cyclosporin (CsA) is the first-line treatment for severe aplastic anemia (SAA) patients who are unfit for transplantation,and the overall response rate (ORR) is about 70%.The utility of eltrombopag (EPAG),a TPO receptor agonist, achieved robust hematologic response in refractory and treatment-naïve SAA patients in clinical trials and some other studies. However, only a few data came from Asia countries where higher incidence of AA has been reported. A retrospective study on the use of EPAG in AA was conducted in mainland China. Aplastic anemia (transfusion dependent non-severe, severe, and very severe) patients who started eltrombopag before Feb 2019 and continued for at least 3 months either as first-line treatment or as rescue treatment, were enrolled. The maximum daily dosage of EPAG used continuously for at least 2 weeks is defined as the stable dosage. Response criteria were referred to that used in previous reports (Townsley DM, NEJM 2017; BCSH, BJH 2016). Fifty-six patients from eleven centers were enrolled in this study, including 26 males and 30 females at the median age of 39 (7-80) years. All patients were transfusion-dependent by the time of EPAG administration, and there were 14 VSAA, 24 SAA and 18 transfusion dependent non-severe aplastic anemia (TD-NSAA). Nineteen treatment-naïve patients received EPAG and IST (ATG+CsA, n=10; CsA/CsA+androgen, n=9) as first-line treatment. Thirty-seven patients were refractory to IST. Eltrombopag was administered at a median dose of 75 (25-150) mg per day for 7 (3-31) month. The median follow-up time was 9 (3-40) months. The overall response rate in patients receiving EPAG as first-line therapy was 78.9% (15/19), and most patients achieved complete response (CR) (10/15). Among the 10 patients receiving ATG+CsA, 6 patients achieved hematologic response (HR) at 3 months post-treatment, including 3 CR. Six patients were diagnosed as VSAA and three achieved HR. For the 9 patients treated with CsA/CsA+androgen, 8 achieved HR (88.9%) and 4 were CR (44.4%) at 3 months. By last follow-up, the cumulative HR rate was 70% in ATG+CsA group and 89% in CsA/CsA+ androgen group. Among the 14 responders, 11 patients receiving EPAG at a stable dosage ≤75mg/d and achieved HR at 3 months. The overall response rate in IST-refractory patients was 46% (17/37), with trilineage response in 27% patients at 3 months. For the 18 ATG+CsA refractory SAA patients,trilineage HR occurred in 4 patients (22.2%, 4/18), bi-lineage HR in one patient and single lineage HR in one patient. Thus, the total HR was 33.3% (6/18) at 3 months and increased to 44% (8/18) by last follow-up. Among the 19 CsA/CsA+ androgen refractory patients, 6 (31.5%, 6/19) achieved trilineage HR, one achieved bi-lineage HR and 4 achieved single lineage response. Total HR rate was 57.9% (11/19) at 3 months after EPAG initiation and 68% (13/19) by last follow-up, including 9 patients with trilineage HR. Among 17 responders, 13 received a stable EPAG dose of≤75mg/d. Most patients tolerated EPAG well. Adverse events occurred in 29 patients (52%) and most were mild to moderate, including gastrointestinal symptom (n=15, e.g. abdominal pain, nausea), impaired liver function (n=5), skin changes (n=7, e.g. skin pruritus and rash) and musculoskeletal pain (n=6), and venous thrombus (n=2). Eltrombopag dosage was reduced in 2 patients due to severe digestive symptoms at 100 mg/d and discontinued in one patient who suffered from upper limb venous thrombus. In conclusion, EPAG is effective and safe in treating Chinese AA patients at a daily dose of 75mg and less. The real-world result of EPAG in Chinese patients is similar to those reported in Western countries. Disclosures No relevant conflicts of interest to declare.

Long Term Discontinuation of Eltrombopag after Remission in Primary Immune Thrombocytopenia: 8-Year Follow-up Data from 15 Spanish Centers

Background: Successful discontinuation of eltrombopag in certain immune thrombocytopenia (ITP) patients after complete response has already been demonstrated. However, the frequency of this phenomenon and type of candidate patients are still matter of discussion. Moreover, possibility of long term discontinuation responses is not clearly established. Methods: Here we retrospectively evaluated our whole cohort of 508 adult patients (aged 18 years or more) with primary ITP treated with eltrombopag included in the Spanish Eltrombopag Registry with a focus on the patients who achieved a durable (at least six months) platelet response after stopping eltrombopag. Successful discontinuation of eltrombopag (SDOE) was defined as those patients who reached remission and maintained platelet counts ≥ 50x109/l for at least 6 months in absence of eltrombopag or any rescue therapies administered. Long term discontinuation of eltrombopag (LTDOE) was defined as those patients who reached remission and maintained platelet counts ≥ 50x109/l for at least 36 months in the absence of eltrombopag or any rescue therapies administered. The study was approved by the Hospital Universitario de Burgos Ethics Committee and fulfilled Helsinki declaration standards. Results: While 37.4% of our patients relapsed of ITP with subsequent platelet count drop sometime during first six months of discontinuation of eltrombopag, a total of 74 patients (14.6%) were able to achieve SDOE. The median age of SDOE patients was 62 [range, 47-79] years. There were 47 women and 27 men. According to the standard definition, patients were allocated to newly diagnosed (n=17), persistent (n=15) and chronic (n=42) ITP groups. The median time from diagnosis to eltrombopag initiation was 31 [range, 4-104] months. The median number of previous therapies was 2 [range, 1-2], including splenectomy (14%), rituximab (18%) and romiplostim (12%). As expected, all patients but 1 achieved a complete response (platelet count ≥100 x 109/L) prior to eltrombopag discontinuation The median duration of eltrombopag treatment was 7 [range, 2-19] months. Reasons for eltrombopag discontinuation were: persistent response despite a reduction in dose over time (n=43), platelet count &gt;400x109/L (n=16), aspartate aminotransferase elevation (n=5), diarrhea (n=4), thrombosis (n=3), patient's request (n=2) and other reasons (n=1). Analysis of these SDOE discontinued patients show that with a median follow-up of 55 [range, 29-79] months, 38 patients (51.3%) maintained treatment-free response 36 months after stopping eltrombopag with no need of additional ITP therapies (median time of eltrombopag discontinuation was 70 [range, 50-77] months).This condition is what we define now as LTDOE. Nevertheless, 36 patients relapsed beyond 6 months but before 36 months of eltrombopag discontinuation (median time of eltrombopag discontinuation was 10 [range,7 -22] months). Characteristics of LTDOE population were a median time since ITP diagnosis of 32 [range, 5-88] months with 15/38 patients having ITP &lt;1 year. 9 patients (24%) were male and their median age was 50 [range, 37-64] years. They had received a median of only two previous treatment lines [range: 1-2 lines]. The median platelet count before starting eltrombopag was 19 x 109/L [range, 8-40]. Meanwhile, platelet count before eltrombopag stop was 218 x 109/L [range, 123-356]. The main characteristics (age, gender, duration of ITP, prior ITP lines, platelet count before starting eltrombopag, duration of eltrombopag treatment, and platelet count before eltrombopag withdrawal) of the 38 patients with LTDOE were compared with those of the SDOE cohort who did not achieve a LTDOE. Unfortunately, no predictive factors of LTDOE could be identified. Conclusion: Durable platelet response following eltrombopag cessation may be observed in only 15% of primary ITP patients treated with this drug. On the contrary, half of patients who achieve a sustained response after eltrombopag withdrawal will get a long term discontinuation. However, we are lacking predictor factors for successful and long-term discontinuation of eltrombopag in primary ITP. Disclosures Gonzalez-Lopez: Amgen: Consultancy, Honoraria, Research Funding, Speakers Bureau; Novartis: Consultancy, Honoraria, Research Funding, Speakers Bureau. Pascual Izquierdo:Novartis: Consultancy; Sanofi: Consultancy. Sánchez-González:Amgen: Consultancy, Speakers Bureau; Gilead: Speakers Bureau; Navartis: Consultancy, Speakers Bureau; Shire: Speakers Bureau; Takeda: Consultancy, Speakers Bureau. Jarque:Takeda: Consultancy, Speakers Bureau; Shire: Consultancy, Speakers Bureau; Shionogi: Consultancy, Speakers Bureau; Servier: Speakers Bureau; Roche: Consultancy, Speakers Bureau; Pfizer: Consultancy, Speakers Bureau; Novartis: Consultancy, Speakers Bureau; MSD: Consultancy, Speakers Bureau; Janssen: Consultancy, Speakers Bureau; Grifols: Consultancy; Gilead: Consultancy, Speakers Bureau; CellTrion: Consultancy; Celgene: Consultancy, Speakers Bureau; Bristol-Myers Squibb: Consultancy, Speakers Bureau; Amgen: Consultancy, Speakers Bureau; Abbie: Consultancy, Speakers Bureau; Alexion: Consultancy, Speakers Bureau.

Eltrombopag: Efficacy and Safety in Steroid Refractory Lupus-Associated Immune Thrombocytopenia.

Eltrombopag, a thrombopoietin receptor agonist, is effective in chronic immune thrombocytopenia (ITP). The data in lupus ITP are sparse. This study aimed to assess the efficacy and safety of eltrombopag in lupus ITP. This is a single-center study conducted between 2012 and 2017 of 12 subjects with systemic lupus erythematosus-associated ITP. Patients with inadequate or suboptimal response to steroids and other immunosuppressants treated with eltrombopag were included in the study. Time taken for response to therapy (defined as platelets >1 lakh), dose, duration of treatment, and adverse effects of the drug were noted. A total of 12 subjects were included in the study. The median platelet count at initiation of eltrombopag was 19,000 per μL. The time taken for response to therapy was 8 days. The median platelet count at 1-month follow-up was 241,000 per μL. All patients were concurrently treated with steroids and other immunosuppressants. Sustained benefit after stopping eltrombopag was noted in all patients. No adverse events including thrombotic complication were noted. Eltrombopag is a new drug in our arsenal for treatment of ITP in lupus. It is a rapidly effective, safe, and orally administered medication. It indirectly contributes to reduction in the dose of steroids and immunosuppressants, thereby minimizing their cumulative adverse effects. It is a promising and safe option for the treatment of lupus-associated thrombocytopenia, but this needs further confirmation from multicenter, multiethnic, randomized controlled trials.

PS1120 IRON MOBILIZATION IN A REAL LIFE COHORT OF APLASTIC ANEMIA PATIENTS TREATED WITH ELTROMBOPAG

Background:Most aplastic anemia (AA) patients are heavily transfusion dependent of both platelets and red blood cells (RBC), and iron overload may become an issue. Excess iron not only hampers the function of several systems (liver, heart, kidney, endocrine system), but has also a negative effect on normal hematopoiesis, which is already particularly poor in AA patients. TPO mimetic eltrombopag (EPAG) improves hematopoiesis in about 40% of patients with both relapsed/refractory and newly‐diagnosed AA, and recent reports demonstrated iron‐mobilizing activity in vitro; furthermore, harmonic oscillation of serum ferritin concomitant to EPAG initiation and discontinuation have been also observed in vivo, indicating an iron mobilization effectAims:To evaluate iron mobilization mediated by EPAG in a real life cohort of AA patientsMethods:Clinical and hematologic parameters, including iron panel, of 10 AA patients treated with EPAG at our Institution in the last 18 months were collected. Changes in iron status and their relationship with EPAG treatment were systematically recordedResults:Table 1 shows hematologic parameters and iron status at baseline and after EPAG treatment. Median age was 43 years (23–91), and male to female ratio 1:1. At the time of EPAG initiation 6 cases presented with severe AA and 60% were RBC transfusion dependent. Three patients were therapy naïve and received EPAG together with frontline IST, starting at 150 mg/day since day+14; seven cases were relapsed/refractory ones, previously treated with ATG and cyclosporine (2), cyclosporine alone (2), or steroids only (2). As regards iron status, ferritin levels and plasma iron increased from EPAG start to month +1 and +3 (p = 0.04), and transferrin saturation was persistently augmented versus baseline at month +1,+3, and +6 (p = 0.01, p = 0.03, P = 0.04, respectively). Considering non transfused patients, we observed a similar increase of these parameters after EPAG start, although baseline values were lower than in transfusion‐dependent cases. At month +12 an amelioration of iron status was observed, both in transfusion dependent and not, particularly iron and transferring saturation that did not further increase. Notably, iron chelation was performed in 2 transfused cases only, possibly accounting for this improvement. Considering hematologic parameters, Hb, ANC, and PLT values significantly ameliorated from baseline to month +3, and along the follow up. Mean Hb increase from baseline was 0.7 ± 1.6 g/dL, mean ANC increase 0.3 ± 0.48x109/L, and mean PLT 27 ± 38x109/L. Transfusion requirement was progressively lost, and ORR increased from 56% at month+3 to 100% at month +6 and thereafter (although CR was observed in 1 patient only)Summary/Conclusion:In our real life cohort of AA patients we observed an increase of iron and transferrin saturation levels soon after EPAG initiation, irrespective of the transfusion status. This data support the iron‐mobilizing effect of EPAGimage

Eltrombopag Rescue for Childhood Severe Acquired Aplastic Anemia after Poor Response to Immunosuppressive Treatment: A Nationwide Study on Behalf of the French Reference Center for Aplastic Anemia

▪Introduction: Thrombopoietin receptor agonist eltrombopag (ELT) provides hematologic improvement in up to 50% of adults with acquired aplastic anemia (AAA) refractory to immunosuppressive therapy (IST). However, current data for ELT efficacy and tolerance in childhood AAA is very limited.Methods: We conducted a multicenter nationwide retrospective study on behalf of the French Reference Center for Aplastic Anemia. Patients under 18 treated with ELT after IST for AAA were included. Lineage responses were defined as follows: red cells transfusion independency or hemoglobin increase of 1.5 g/dL, platelets transfusion independency or a 20 G/L increase in platelets counts, doubling of the neutrophil count or an increase above 0.5 G / L.Results: We identified 12 children (2-17 years old, mean 9.5±5.9 years) treated for severe (7) /very severe (5) AAA with horse ATG and cyclosporine as first-line treatment between 2014 and 2018 in five different centers. Minor PNH clone was identified at diagnosis in two patients. All patients had a normal bone-marrow karyotype and FISH. None had a matched related donor. Median time between IST onset and eltrombopag initiation was 3.5 months [1-46]. All patients still met severe aplastic anemia criteria and needed RBC and platelet transfusions at ELT initiation. Mean hemoglobin, reticulocytes, platelets and neutrophils values were 7.3±0.8 g/dL, 24.5±24 G/L, 11±5.9 G/L and 0.8±0.7 G/L. Seven patients had received IST for more than 3 months and were therefore considered refractory to this treatment. ELT was indicated for an uncontrolled bacterial infection in 2 patients one and two months after IST initiation. One patient received an excessive dose of 12.5 mg/kg/day. Average ELT dosage for the other patients was 2±0.6 mg/kg/d. The median duration of treatment with ELT was 5.5 months [1-10]. After ELT initiation, nine patients (75%) reached hematological response for at least one cell line with no additional treatment. In these patients, hemoglobin increased on average by 3±1.3 g/dL, neutrophils by 2.5±3.5 G/L and platelets by 89.8±39.7 G/L. Seven patients (58%) achieved a trilineage response and were both RBC and platelets transfusions independent after 1 month (1), 3 months (3) and six months (7). Five patients (41.6%) reached a robust response (platelets > 50 G/L, hemoglobin > 10 g/dL, neutrophils > 1 G/L). All these trilineage responders were still on cyclosporine at the time of last assessment. ELT was withdrawn in 4 trilineage responders. Two of them still fulfilled robust response criteria 3 and 43 months after ELT withdrawal while the 2 others required occasional transfusions. The 3 others trilineage responders who were still receiving ELT remained transfusion independent 6 (2) and 11 (1) months after ELT initiation. Two patients (16.6%) had a unique lineage response: one was lost of view and one developed a myelodysplasia with RUNX1 mutation 3 months after ELT initiation. He is alive 8 months after HSCT. No clonal evolution was reported in the 5 other patients for whom cytogenetics follow-up was available. No response was achieved in 3 patients (25%), all of whom were treated for less than 3 months: ELT was withdrawn for deemed inefficiency in 2 patients (16.6%) after 1 and 2 months respectively and for toxicity (disseminated intravascular coagulation) in another patient after 2 months. These patients underwent HSCT. One patient died of graft failure 3 months after HSCT. Overall, eleven patients (91%) were alive 13.4±5.6 months after eltrombopag onset. Disseminated intravascular coagulation occurred in a 2 years patient who received a large ELT dosage (12.5 mg/Kg). No other grade III-IV toxicity was reported.Discussion/Conclusion: This is the first report of ELT for childhood severe AAA after IST. Eltrombopag was overall well tolerated. We observed a high rate of sustained trilineage response as reported in adult patients and only 1 case of clonal evolution which is a known complication in non-responsive AAA. Onset of the trilinear hematologic responses is progressive and achieved 3-6 months after ELT initiation. A longer follow-up of this cohort is mandatory to assess response durability and clonal evolution final risk. Nevertheless, we propose that ELT should be considered for severe AAA non-responsive to IST after 3 months of treatment especially if only an alternative donor is available. [Display omitted] DisclosuresNo relevant conflicts of interest to declare.