Efficacy and safety of eltrombopag in combination with dexamethasone as first‐line treatment in adult patients with newly diagnosed immune thrombocytopenia

Left panel: Scheme of the XPAG-ITP trial. The dexamethasone monotherapy (DEX) arm consisted of DEX 40 mg/day for days 1–4 for one to three cycles every 28 days to a maximum of 12 weeks, cycles 2 + 3 were optional. Patients randomised to eltrombopag combined with dexamethasone (ETB + DEX) received eltrombopag (ETB) in combination with a short course of high-dose DEX beginning on day 1 (40 mg/day during days 1–4). The starting dose of ETB was 50 mg/day for 2 weeks; thereafter, the ETB dose was increased by 25 mg for all patients who did not achieve the target platelet count of ≥50 × 109/L. The ETB tapering was performed by decreasing the dose by 25 mg every 2 weeks to a minimum dose of 25 mg every other day for all patients. Right upper panel: Clinical outcomes in patients treated with first-line ETB + DEX. Patients displayed a qualitatively longer response duration and qualitatively reduced usage of rescue medication. Right lower panel: The immunological T-cell response was different in treatment responders and non-responders. Patients with sustained response (responders) displayed a high T-cell clonality at baseline. Clones are depicted as bubbles (right side). MB received institutional research grants from Merck, BMS, Hexal, German Cancer Aid (Krebshilfe), German Research Foundation and the Federal Ministry of Education and Research as well as honoraria for lectures and advisory board meetings by Celgene, Janssen, Gilead, Merck, Roche, Amgen, Sanofi-Aventis and BMS. She received funding for the translational research programme of the XPAG-ITP trial from Novartis. SJ, CQ, FR and TT are Novartis Pharma GmbH employees. FR is a stock owner of Novartis Pharma GmbH. MH has received speaker honoraria and consulting fees from Novartis, Roche, Amgen, Takeda, GSK, Jazz Pharmaceuticals, Bayer Vital, Celgene, Gilead, Sanofi and Sobi. MH travelling costs were covered by AbbVie. OM has received speaker honoraria and consulting fees from Amgen, Argenx, Grilfols, Novartis and SOBI. AM received consulting fees and payment for expert testimony from Novartis, Grifols, Sanofi, Swedish Orphan Biotech, Amgen. Furthermore, AM was supported financially to attend meetings by Grifols and Swedish Orphan Biotech; AM holds stock of Johnson & Johnson and Roche. KT-G has received speaker honoraria and consulting fees from Amgen, Grifols, GSK, Novartis, Roche, Sanofi, Sobi and Takeda. TS received research support by Novartis, SOBI, Amgen, Argenx, Grifols and Sanofi, and further consulting fees from Novartis, speaker honoraria by Novartis, Amgen, Alexion, Jannsen, AOP, SOBI, Argenx, Grifols and Astra Zeneca; TS is member of the scientific advisory board for Novartis, Amgen, Argenx; additionally, he receives funding from Celgene/BMS. OB is founder of miri dynamics. All other authors declare no potential conflict of interest. Clinical data were collected in the respective clinical centres. Derived data supporting the findings of this study are available from the corresponding author MB on request. Figure S1. Scheme of the XPAG-ITP trial and consort diagram of the XPAG-ITP trial. Table S1. Patient disposition (all patients enrolled/screened). Table S2. Diagnosis and extent of disease (FAS). Table S3. Demographic summary, baseline characteristics (FAS) and treatment exposure. Table S4. Platelet counts [109/L] at selected visits (FAS) and time point at which platelet count achieved ≥30 × 109/L. Table S5. Characterisation of patients with sustained response by week 52. Table S6. Sample statistics of platelet count [109/L] at discontinuation of study medication, by sustained response off treatment at week 52 (FAS). Table S7. Overview of ITP-directed rescue medication or procedure/non-drug therapy, duration. Table S8. Reasons for non-sustained response off treatment at week 52 (FAS). Table S9. Adverse (AE) and severe adverse events (SAE), FAS. Table S10. Adverse events (AE) related to study treatment by preferred term occurring in >1% in total, FAS. Please note: The publisher is not responsible for the content or functionality of any supporting information supplied by the authors. Any queries (other than missing content) should be directed to the corresponding author for the article.