A Phase 1b Study of Eltrombopag and Azacitidine in Patients with High Risk Myelodysplastic Syndromes and Related Disorders

• Published in: Blood 2020-11, Vol.136 (Supplement 1), p.10-10
• Main Authors: Sternberg, Alex, Boucher, Rebecca H., Coulthard, Helen C, Raghavan, Manoj, Culligan, Dominic J., Jackson, Aimee, Cargo, Catherine, Dennis, Mike, Metzner, Marlen, Moore, Rachel, Bowen, David, Vyas, Paresh
• Format: Article
• Language: English
• ISSN: 0006-4971; 1528-0020
• DOI: 10.1182/blood-2020-134227

Background: Azacitidine (AZA) based therapy is a standard of care in IPSS INT-2/High MDS/low blast count AML and CMML-2. Thrombocytopenia is an adverse prognostic factor in MDS; increased severity correlates with haemorrhagic complications and shorter AML progression time, and early platelet recovery after AZA is linked to better outcomes. Accumulation of AZA doses is important to patient response, but initial treatment with AZA can aggravate thrombocytopenia and impact outcome. Eltrombopag (ELT) is a thrombopoietin receptor (TpoR) agonist approved for adult chronic immune thrombocytopenic purpura. ELT has shown efficacy in low risk MDS and reduces thrombocytopenic events in advanced MDS and AML. The ELASTIC trial (ISRCTN05858391) is a single-arm phase 1b dose-finding study examining the safety and tolerability of ELT/AZA in patients with MDS/AML with expansion cohort (n=10) at MTD. We investigated if ELT/AZA would lead to earlier platelet recovery and improve AZA efficacy. Although a Phase 3 study testing ELT/AZA (SUPPORT) was terminated due to futility during the ELASTIC trial, we reasoned that drug sequencing may affect outcome. As ELASTIC patients received an ELT pre-phase, ELASTIC was run to completion. Methods: Patients with IPSS INT-2 or High MDS/CMML-2/AML