Background: Eltrombopag is a thrombopoietin receptor agonist (TPO-RA) approved for treating chronic primary ITP patients. Nevertheless, due to the non-existence of clinical trials there are no clear efficacy and safety data of eltrombopag in secondary ITP. Aims: To evaluate the efficacy and safety results using eltrombopag for treating secondary ITP patients in routine clinical practice in Spain. Methods: 33 secondary ITP patients from 23 Spanish centers who had been treated with eltrombopag and included in the Spanish Eltrombopag ITP Registry were retrospectively evaluated. However, 5 patients were excluded from the final analysis because three of them were aplastic anaemias, one was an amegakaryocytic thrombocytopenia and another one was a acute myeloid leukemia related thrombocytopenia. Results: Our secondary ITP case series included nine hepatitis C virus-ITP, five lymphoproliferative disorders, four systemic lupus erythematosus (SLE), three HIV-ITP, two synchronous HCV-HIV-ITP, two psoriatic arthritis, one Evans Syndrome, one common variable immunodeficiency and one Sjögren syndrome. The median age of our cohort was 54 (IQR, 35-66) years. There were 17 women and 11 men. 25% of patients had a Charlson Comorbidity Index score of 2 or more at diagnosis. The median time from secondary ITP diagnosis to eltrombopag initiation was 36 (IQR, 1-76) months. The median number of therapies before starting eltrombopag was 2 (IQR, 1-4), including rituximab (28%), romiplostim (17%) and splenectomy (10%). At the time of treatment start, 15 of 28 patients (53%) patients were receiving concomitant treatment for secondary ITP, mainly including corticosteroids (31%) or immunoglobulins (21%). 7 of 28 (25%) patients had bleeding symptomatology during the month preceeding the starting eltrombopag. At eltrombopag initiation the median platelet count was 9x109/L (IQR, 6-15x109/L). 25 of 28 (89%) patients responded to eltrombopag treatment. 23 patients (82%) achieved a complete response (CR; platelet count >100x109/L). To point out that 2 patients needed concomitant treatment with low prednisone doses to achieve or maintain the response. It was a slight difference between men and women regarding the response and complete response rates obtained: men achieved 82% and 73% respectively meanwhile women achieved 94% and 83%. The proportion of patients achieving platelet response was quite similar regardless the other studied parameters: age (87% and 92% for patients <65 years-old and ≥65 years-old, respectively), use of concomitant ITP medication at baseline (87% and 93% for patients with and without concomitant baseline ITP medication use) and bleeding at starting eltrombopag (100% and 87% for patients with and without bleeding, respectively). Three patients achieved complete response after only one month of tretament without relapsing afterwards. In five patients splenectomy was made few months after eltrombopag treatment (3 patients were in CR). Only two patients failed to achieve response with eltrombopag treatment: common variable immunodeficiency and one HIV patients. After a 9 months median follow-up, 15 patients maintain the response. Only 3 patients relapsed from their disease. Only two adverse events were reported: a grade 2-3 cephalea in a SLE patient and a death caused by respiratory insufficiency in a HIV patient with a CR ITP at that moment. Summary and Conclusions: Our case series describe the great efficacy and safety results observed with the use of eltrombopag in our secondary ITP patients. Our data suggest some diseases may not benefit from the use of eltrombopag. However more studies are needed to confirm the possible usefulness of TPO-RAs in this variety of secondary ITP cases.

Background: Eltrombopag is a thrombopoietin receptor agonist (TPO-RA) approved for treating chronic primary ITP patients. Nevertheless, due to the non-existence of clinical trials there are no clear efficacy and safety data of eltrombopag in secondary ITP. Aims: To evaluate the efficacy and safety results using eltrombopag for treating secondary ITP patients in routine clinical practice in Spain. Methods: 33 secondary ITP patients from 23 Spanish centers who had been treated with eltrombopag and included in the Spanish Eltrombopag ITP Registry were retrospectively evaluated. However, 5 patients were excluded from the final analysis because three of them were aplastic anaemias, one was an amegakaryocytic thrombocytopenia and another one was a acute myeloid leukemia related thrombocytopenia. Results: Our secondary ITP case series included nine hepatitis C virus-ITP, five lymphoproliferative disorders, four systemic lupus erythematosus (SLE), three HIV-ITP, two synchronous HCV-HIV-ITP, two psoriatic arthritis, one Evans Syndrome, one common variable immunodeficiency and one Sjögren syndrome. The median age of our cohort was 54 (IQR, 35-66) years. There were 17 women and 11 men. 25% of patients had a Charlson Comorbidity Index score of 2 or more at diagnosis. The median time from secondary ITP diagnosis to eltrombopag initiation was 36 (IQR, 1-76) months. The median number of therapies before starting eltrombopag was 2 (IQR, 1-4), including rituximab (28%), romiplostim (17%) and splenectomy (10%). At the time of treatment start, 15 of 28 patients (53%) patients were receiving concomitant treatment for secondary ITP, mainly including corticosteroids (31%) or immunoglobulins (21%). 7 of 28 (25%) patients had bleeding symptomatology during the month preceeding the starting eltrombopag. At eltrombopag initiation the median platelet count was 9x109/L (IQR, 6-15x109/L). 25 of 28 (89%) patients responded to eltrombopag treatment. 23 patients (82%) achieved a complete response (CR; platelet count >100x109/L). To point out that 2 patients needed concomitant treatment with low prednisone doses to achieve or maintain the response. It was a slight difference between men and women regarding the response and complete response rates obtained: men achieved 82% and 73% respectively meanwhile women achieved 94% and 83%. The proportion of patients achieving platelet response was quite similar regardless the other studied parameters: age (87% and 92% for patients <65 years-old and ≥65 years-old, respectively), use of concomitant ITP medication at baseline (87% and 93% for patients with and without concomitant baseline ITP medication use) and bleeding at starting eltrombopag (100% and 87% for patients with and without bleeding, respectively). Three patients achieved complete response after only one month of tretament without relapsing afterwards. In five patients splenectomy was made few months after eltrombopag treatment (3 patients were in CR). Only two patients failed to achieve response with eltrombopag treatment: common variable immunodeficiency and one HIV patients. After a 9 months median follow-up, 15 patients maintain the response. Only 3 patients relapsed from their disease. Only two adverse events were reported: a grade 2-3 cephalea in a SLE patient and a death caused by respiratory insufficiency in a HIV patient with a CR ITP at that moment. Summary and Conclusions: Our case series describe the great efficacy and safety results observed with the use of eltrombopag in our secondary ITP patients. Our data suggest some diseases may not benefit from the use of eltrombopag. However more studies are needed to confirm the possible usefulness of TPO-RAs in this variety of secondary ITP cases.

BACKGROUND:

While chimeric antigen receptor (CAR) T-cell therapy has revolutionized the treatment outcomes of relapsed/refractory hematological malignancies, this therapy is associated with post-treatment cytopenias, which can pose a challenge to its safe administration. This study describes the management of post-CAR T cytopenias using the thrombopoietin mimetic eltrombopag.

METHODS:

This retrospective analysis included adult patients with lymphoma or myeloma who received CAR T-cell therapy at two academic medical centers. Eltrombopag was initiated for patients who had persistent high-grade leukopenia and/or thrombocytopenia beyond 21 days post-CAR T infusion. Risk factors and outcomes were assessed and compared for patients who did or did not receive eltrombopag.

RESULTS:

Among the 185 patients analyzed, a majority (88%) experienced thrombocytopenia or leukopenia at day +30 post-CAR T infusion. A total of 42 patients met the criteria for eltrombopag treatment and initiated therapy. Patients who received eltrombopag were more likely to have pre-existing cytopenias at lymphodepletion, receive bridging therapy, experience an infection, or require intensive care. Recovery from cytopenias occurred within 180 days for a majority (94%) of patients.

CONCLUSIONS:

The use of eltrombopag for post-CAR T leukopenia and thrombocytopenia was considered safe without any significant toxicities. The use of eltrombopag for post-CAR T cytopenias might be effective in a high-risk patient population but requires further study.

Background: Thrombopoietin receptor (TPO) agonists are licensed for immune thrombocytopenia purpura ITP). Potential for use in other thrombocytopenic conditions is being explored. Aims: Our aim was to demonstrate the efficacy of eltrombopag in ITP -whether for severe disease or bridging therapy for surgery or chemotherapy. We also examined the use of eltrombopag in malignancy-associated thrombocytopenia, whether from disease or chemotherapy. Methods: We retrospectively identified all patients who had received eltrombopag from a single institution. Patients were identified who had received eltrombopag as part of standard treatment pathways, as well as those for whom special consideration was sought (ie refractory thrombocytopenia in advanced malignancy). Eltrombopag was commenced from between March 2012 (as the first documented prescription time point) to January 2016. For ITP, we included those deemed to have a 'severe' phenotype according to the international consensus guidelines. All patients fulfilled these criteria, warranting second-line treatment beyond steroids and IVIg. Many had failed multiple previous lines or had comorbidities limiting options. For non-ITP thrombocytopenic patients, indication for eltrombopag was examined on a case-by-case basis, according to benefit versus risk, since prescription was off-label. The primary indication was to enable chemotherapy, based on oncology requirements for platelet counts >100x109/L. Results: Our total cohort of 62 patients (36 males and 26 females) was treated over 8 years. This included 50 ITP patients requiring treatment for severe/refractory disease (n= 36), or bridging therapy (n=14). In the refractory group, 25 patients had primary ITP and 11 secondary ITP; including HIV (n=5), viral (n=2) malignancy (n=1) and other autoimmune aetiologies (n=3). Follow up was 1 to 85 months (median 12.5 months), with median 4 previous lines of therapy. Median time between ITP diagnosis and eltrombopag commencement was 24 months in the refractory ITP group. The delay was partially due to eltrombopag availability. In the overall ITP cohort (n=50), complete response (CR) was achieved in 28 patients (56%), partial response (PR) in 19 (38%) and no response (NR) in 3 patients (6%). Median time to response was 3 weeks (1 to 44 weeks). At follow up, 17 patients were in CR (34%) and 29 patients in PR (58%). Eltrombopag dose ranged from 25 to 100mg daily, with a median of 25mg (n=12). The difference in response at follow up was due to dose reduction, whilst maintaining haemostatic platelet counts. The malignancy-associated group included 12 patients. Eltrombopag use achieved CR in 6 patients (50%), PR in 3 (25%) and NR in 3 (25%). Summary/Conclusions: In conclusion, eltrombopag use in the severe ITP setting achieved a response in 94% cases. For severe or refractory disease, dose reduction was possible once response achieved. Although not CR by strict definition, a safe platelet count could be maintained- typically >50x109/Lwithout bleeding sequelae. In the bridging cohort, eltrombopag proved a reliable means of improving platelet counts for intervention, without the problems associated with steroids or IVIg. Beyond ITP, eltrombopag may be of practical benefit during chemotherapy and other myelosuppressive treatment, to ensure optimal dosing of these therapies via platelet count support. Although our non-ITP cohort was small, CR was achieved in half of these patients. Further trials are needed to demonstrate which patients may benefit from eltrombopag during treatment for malignancy-associated thrombocytopenia.

This open-label, repeat dosing study, TRA108057, will evaluate the efficacy, safety and tolerability of eltrombopag, when administered in a repeat, cyclic dosing schedule. The study will describe the effect of repeated (3 cycles), intermittent dosing of eltrombopag on the pharmacodynamics and durability of eltrombopag response as measured by the peripheral platelet counts.

For more information or to see if you qualify, please visit: http://www.itpstudy.com/gov

Pretreatment blood counts, particularly an absolute reticulocyte count ≥25×109/L, correlate with response to immunosuppressive therapy in severe aplastic anemia. In recent trials, eltrombopag combined with standard immunosuppressive therapy yielded superior responses than those to immunosuppressive therapy alone. Our single institution retrospective study aimed to elucidate whether historical predictors of response to immunosuppressive therapy alone were also associated with response to immunosuppressive therapy plus eltrombopag. We sought correlations of blood counts, thrombopoietin levels and the presence of paroxysmal nocturnal hemoglobinuria clones with both overall and complete responses in 416 patients with severe aplastic anemia, aged 2-82 years (median, 30 years), initially treated with immunosuppressive therapy plus eltrombopag between 2012 and 2019 (n=176) or with immunosuppressive therapy alone between 1999 and 2010 (n=240). Compared to non-responders, patients in the group of overall responders to immunosuppressive therapy plus eltrombopag had significantly higher pretreatment absolute reticulocyte counts, higher neutrophil counts and reduced thrombopoietin levels, as also observed for the group treated with immunosuppressive therapy alone. Addition of eltrombopag markedly improved the overall response in subjects with an absolute reticulocyte count between 10-30×109/L from 60% (54 of 90) to 91% (62 of 68). Absolute lymphocyte count correlated with complete response in the groups treated with immunosuppressive therapy with or without eltrombopag, especially in adolescents aged ≥10 years and adults, but the correlation was reversed in younger children. Platelet count and the presence of a paroxysmal nocturnal hemoglobinuria clone did not correlate with responses to immunosuppressive therapy. Blood counts remain the best predictors of response to nontransplant therapies in severe aplastic anemia. Addition of eltrombopag to immunosuppressive therapy shifted patients with a lower absolute reticulocyte count into a better prognostic category.

Chronic immune thrombocytopenia (ITP) is an autoimmune disease that results in chronically low platelet counts. Treatment guidelines recommend a platelet count of at least 50,000/µl before minor surgery and at least 80,000/µl before major surgery. This retrospective analysis explored invasive non-dental procedures associated with the risk of bleeding (hemostatic challenges) among patients with chronic ITP in five phase 2/phase 3 studies of the thrombopoietin-receptor agonist, eltrombopag. Data collection for patients who underwent hemostatic challenges included demographics, study medication, timing of the procedure, platelet counts at last assessment before and first assessment after the procedure, supplemental ITP treatment, and bleeding events. Among 494 patients who participated in the studies, 87 hemostatic challenges were recorded. Median platelet counts before 44 major procedures in 32 patients were 100,000/µl and 18,500/µl among patients who received eltrombopag and placebo, respectively; before 43 minor procedures in 38 patients, median platelet counts were 82,000/µl and 20,000/µl among patients who received eltrombopag and placebo, respectively. A minority of patients required supplemental ITP treatment. Only 2 of 87 hemostatic challenges were associated with bleeding events; both patients received eltrombopag and pre-procedural platelet counts were 83,000/µl and 2000/µl. Although the number of patients who did not undergo procedures due to thrombocytopenia was not captured, these data suggest a majority of patients with chronic ITP who receive eltrombopag and experience increases in platelet counts meet current pre-procedural platelet count recommendations. The potential role of eltrombopag in supporting preparation of chronic ITP patients for surgical procedures still needs to be clinically established.

The purpose of this study was to evaluate the efficacy of eltrombopag for poor graft function (PGF) on overall hematologic response (partial and complete), as determined by platelet, hemoglobin and neutrophil counts by 16 weeks after the initiation of eltrombopag in patients with poor graft function after allogeneic hematopoietic stem cell transplantation (allo-HSCT).

MYH9-Related Disease (MYH9-RD) is one of the less rare forms of inherited thrombocytopenia. It derives from mutations of the gene MYH9 for the heavy chain of nonmuscle myosin IIA and is characterized by congenital macrothrombocytopenia variably associated with young-adult onset of hearing loss, cataract, and a severe proteinuric nephropathy. Only platelet transfusions are available for increasing platelet counts in this condition, but they expose to the risks of acute reactions, transmission of infectious diseases, and refractoriness to subsequent platelet transfusions. Moreover, this treatment suffers from scarceness of blood donors. Novel thrombopoiesis-stimulating agents have been developed and 2 of them, eltrombopag and romiplostin, have been approved for increasing platelet count in a few forms of acquired thrombocytopenia. Since it has been recently shown that megakaryocytes of patients with MYH9-RD respond in vitro to TPO stimulation, we reasoned that TPO-mimetics could be effective also in this condition and decided to test the effect of eltrombopag. Therefore, we performed a phase II, multicentre, open-label, dose escalation trial. Twelve adult patients with a platelet count lower than 50x10e9/L and a diagnosis of MYH9-RD confirmed by identification of the causative MYH9 mutations received orally eltrombopag 50 mg daily for 21 days (Revolade®, GSK). Patients with platelet counts lower than 100x10e9/L at day 21 increased eltrombopag to 75 mg daily for 21 additional days. Patients with platelet counts between 100 and 150x10e9/L at day 21 continued eltrombopag 50 mg daily for the following 21 days, while patients with more than 150x10e9 platelets/L stopped therapy. The primary endpoints were the achievement of a platelet count over 100x10e9/L or at least three times the baseline value (major response), or at least twice the baseline value but less than major response (minor response). Secondary end points included safety and tolerability, and the reduction of bleeding tendency. After 3 weeks at the eltrombopag dose of 50 mg daily, 3 patients achieved platelet counts of 150x10e9/L or more and stopped therapy. Two had a platelet counts between 100 and 150x10e9/L and continued treatment at the same dosage, while 7 had less than 100x10e9 platelets/L and received eltrombopag 75 mg daily for 3 weeks. A major response was obtained in 8 patients (67%), in 5 of them after 3 weeks of eltrombopag 50 mg daily, and in 3 cases after 3 additional weeks at the dose of 75 mg. Three patients (25%) achieved a minor response, 1 after 3 weeks at 50 mg daily, and 2 after 3 additional weeks at 75 mg. In one patient the treatment resulted in no response. Mean platelet count at the end of treatment was significantly higher than at baseline (105 versus 31x10e9 platelets/L, p=0.0022). In the 11 patients that achieved major or minor responses, mean platelet count was still higher than baseline 15 days after discontinuation of the drug, while it returned to levels near baseline 15 days later. Platelet size did not change either during treatment or after its cessation, and this indicates that the increases in platelet count were paralleled by corresponding increases in total platelet mass. The extent of platelet aggregation was within the normal range after all tested agonists in 5 of the 7 patients that achieved platelet counts higher than 100x10e9/L, while it was slightly reduced after ADP and collagen in 2 patients. Mean serum TPO level was higher than the normal range and this figure did not change neither during treatment with eltrombopag nor after its discontinuation. Ten of 12 patients had grade 1 or 2 bleeding symptoms, as measured by the WHO bleeding scale, at baseline, while 2 were asymptomatic. Upon treatment, bleeding diathesis quickly ameliorated and disappeared in 8 cases, while it remained unchanged in the only patient with no response to eltrombopag and in another one with a minor response. The benefit in terms of bleeding diathesis lasted well beyond treatment discontinuation. Treatment was well tolerated in all cases, with only two patients reporting mild and transient headache and one patient suffering from transient dry mouth at the beginning of treatment. In conclusion, 50-75 mg of eltrombopag per day increased platelet count and reduced bleeding tendency in most patients with MYH9-RD. Further research is required to ascertain whether TPO mimetics are effective also in other forms of inherited thrombocytopenia.

The primary objective is to compare the efficacy of eltrombopag vs rhTPO in complete response in patients after HSCT in China. This is a post-marketing, interventional, single-center, double-arm, prospective, open-label, non-inferior, randomized controlled study in adult patients with hematopoietic stem cell transplantation in China. Patients will be recruited consecutively from the study sites during the enrollment period. The enrolled patients will be given eltrombopag or rhTPO under the conditions of informed consent and frequent monitoring according to the clinical guideline.