Introduction: Eltrombopag has been marketed in Europe in 2010 for the treatment of chronic primary immune thrombocytopenia (ITP) lasting 12 months or longer from diagnosis, refractory to other treatments in splenectomized patients or patients who are contraindicated for splenectomy. Based on results of clinical trials, this marketing indication has been modified in 2019 for the treatment of patients aged 1 year and above with primary ITP lasting 6 months or longer from diagnosis and who are refractory to other treatments. However, data are lacking regarding the use, the efficacy and the safety of eltrombopag in the clinical practice in Europe. The ELEXTRA study was aimed at assessing these questions in France.

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 for ITP in routine visit or hospital stay 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 <100 x 109/L and exclusion of other causes of thrombocytopenia. Study population consisted in all incident ITP adults included in the CARMEN-France registry from June 2013 to December 2018 and exposed to eltrombopag during the disease course. We described the time of exposure to eltrombopag from ITP diagnosis and patients' characteristics. Efficacy was assessed in patients who had a platelet count <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 exposure to eltrombopag were collected and assessed using the World Health Organization causality assessment scale. All ADRs at least "possible" were described.

Results: Out of 552 patients included in the registry, 81 (14.7%) had been exposed to eltrombopag for a median duration of 92 days (range: 1-1523). Mean age was 60.9 years (standard deviation: 20.9) and 45 (55.6%) were males; 36 (44.4%) had at least one comorbidity of the Charlson Comorbidity Index score; 45 (55.6%) had at least one cardiovascular risk factor (not including age and sex) and 4 (4.9%) a history of venous thrombosis. At ITP diagnosis, median platelet count was 7 x 109/L (range: 1-88 x 109/L) and 67 (82.7%) patients had bleeding. Median time from ITP onset to first exposure to eltrombopag was 2.7 months (range: 0.2-72.2): 43 (53.1%) patients were exposed before 3 months of ITP duration, 8 (9.9%) between 3 and 6 months, 18 (22.2%) between 6 and 12 months and 12 (14.8%) after 12 months. Exposures to ITP treatments before eltrombopag initiation were: corticosteroids in 75 (92.6%) patients, intravenous immunoglobulin (IVIg) in 61 (75.3%), dapsone in 15 (18.5%), rituximab in 14 (17.3%), romiplostim in 10 (12.3%), hydroxychloroquine in 9 (11.1%), danazol in 5 (6.2%), vinblastine in 3 (3.7%), azathioprine in 1 (1.2%), ciclosporin in 1 (1.2%) and splenectomy in none. Eltrombopag was used as second-line agent in 24 (28.6%) patients and third-line in 20 (24.7%). Among the 81 patients, 39 (48.1%) had a platelet count <30 x 109/L at eltrombopag initiation; 34 (87.2%) achieved overall response and 31 (79.5%) complete response. These response rates were stable across disease duration phases (<3 months, 3-6 months and >6 months), age groups (<60 vs. ≥60 years), Charlson Comorbidity Index score (0, 1-2 and ≥3). Among the 34 patients who achieved overall response, 29 (85.3%) had a concomitant exposure to ITP treatment at eltrombopag initiation (including steroids, n=12; IVIg during the past month, n=15; rituximab in the past 6 months, n=5). Overall, 17 ADRs were reported: the most frequent were: rash (n=3), thrombosis (n=3: 1 deep vein thrombosis, 1 pulmonary embolism and 1 ischemic stroke), thrombocytosis (n=2), hepatitis (n=2) and bronchitis (n=2).

Conclusion: In the French real-life practice, eltrombopag is used early in ITP course. Efficacy is similar to efficacy in clinical trials, and is stable by subgroups of patients. The profile of ADRs identified in clinical trials is also confirmed. Introduction: Eltrombopag has been marketed in Europe in 2010 for the treatment of chronic primary immune thrombocytopenia (ITP) lasting 12 months or longer from diagnosis, refractory to other treatments in splenectomized patients or patients who are contraindicated for splenectomy. Based on results of clinical trials, this marketing indication has been modified in 2019 for the treatment of patients aged 1 year and above with primary ITP lasting 6 months or longer from diagnosis and who are refractory to other treatments. However, data are lacking regarding the use, the efficacy and the safety of eltrombopag in the clinical practice in Europe. The ELEXTRA study was aimed at assessing these questions in France.

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 for ITP in routine visit or hospital stay 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 <100 x 109/L and exclusion of other causes of thrombocytopenia. Study population consisted in all incident ITP adults included in the CARMEN-France registry from June 2013 to December 2018 and exposed to eltrombopag during the disease course. We described the time of exposure to eltrombopag from ITP diagnosis and patients' characteristics. Efficacy was assessed in patients who had a platelet count <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 exposure to eltrombopag were collected and assessed using the World Health Organization causality assessment scale. All ADRs at least "possible" were described.

Results: Out of 552 patients included in the registry, 81 (14.7%) had been exposed to eltrombopag for a median duration of 92 days (range: 1-1523). Mean age was 60.9 years (standard deviation: 20.9) and 45 (55.6%) were males; 36 (44.4%) had at least one comorbidity of the Charlson Comorbidity Index score; 45 (55.6%) had at least one cardiovascular risk factor (not including age and sex) and 4 (4.9%) a history of venous thrombosis. At ITP diagnosis, median platelet count was 7 x 109/L (range: 1-88 x 109/L) and 67 (82.7%) patients had bleeding. Median time from ITP onset to first exposure to eltrombopag was 2.7 months (range: 0.2-72.2): 43 (53.1%) patients were exposed before 3 months of ITP duration, 8 (9.9%) between 3 and 6 months, 18 (22.2%) between 6 and 12 months and 12 (14.8%) after 12 months. Exposures to ITP treatments before eltrombopag initiation were: corticosteroids in 75 (92.6%) patients, intravenous immunoglobulin (IVIg) in 61 (75.3%), dapsone in 15 (18.5%), rituximab in 14 (17.3%), romiplostim in 10 (12.3%), hydroxychloroquine in 9 (11.1%), danazol in 5 (6.2%), vinblastine in 3 (3.7%), azathioprine in 1 (1.2%), ciclosporin in 1 (1.2%) and splenectomy in none. Eltrombopag was used as second-line agent in 24 (28.6%) patients and third-line in 20 (24.7%). Among the 81 patients, 39 (48.1%) had a platelet count <30 x 109/L at eltrombopag initiation; 34 (87.2%) achieved overall response and 31 (79.5%) complete response. These response rates were stable across disease duration phases (<3 months, 3-6 months and >6 months), age groups (<60 vs. ≥60 years), Charlson Comorbidity Index score (0, 1-2 and ≥3). Among the 34 patients who achieved overall response, 29 (85.3%) had a concomitant exposure to ITP treatment at eltrombopag initiation (including steroids, n=12; IVIg during the past month, n=15; rituximab in the past 6 months, n=5). Overall, 17 ADRs were reported: the most frequent were: rash (n=3), thrombosis (n=3: 1 deep vein thrombosis, 1 pulmonary embolism and 1 ischemic stroke), thrombocytosis (n=2), hepatitis (n=2) and bronchitis (n=2).

Conclusion: In the French real-life practice, eltrombopag is used early in ITP course. Efficacy is similar to efficacy in clinical trials, and is stable by subgroups of patients. The profile of ADRs identified in clinical trials is also confirmed.

Disclosures

Moulis:Novartis pharma: Research Funding, Speakers Bureau; Amgen pharma: Research Funding, Speakers Bureau; CSL Behring: Research Funding.

OffLabel Disclosure:

Eltrombopag was used off-label in some patients in this real-life study

Author notes

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Asterisk with author names denotes non-ASH members.