Phase Ib study of eltrombopag and azacitidine in patients with high-risk myelodysplastic syndromes and related disorders (the ELASTIC study)
Authors
Sternberg, A.Boucher, R.
Coulthard, H. C.
Raghavan, M.
Culligan, D.
Jackson, A.
Cargo, C.
Dennis, Michael
Metzner, M.
O'Sullivan, J.
Moore, R.
Bowen, D.
Vyas, P.
Affiliation
Department of Haematology, Great Western Hospital, Swindon, UKIssue Date
2022
Metadata
Show full item recordAbstract
Treating adverse risk myelodysplastic syndromes with azacitidine exacerbates thrombocytopenia. We report a study of eltrombopag in combination with azacitidine using a 3 + 3 cohort design. Patients with baseline platelets of <150 × 109 /l received eltrombopag ranging from 25 to 300 mg. An 8-day pre-phase of eltrombopag was followed by two cycles of combined therapy. Amongst 31 patients, there were no dose-limiting toxicities. The maximum tolerated dose (MTD) was 300 mg. Transient increases in bone marrow blasts at day 8 were common but no patient had protocol-defined progression following eltrombopag monotherapy. Marrow response rates after three and six treatment cycles were 32% and 29% respectively. In all, 70% of patients treated below and 36% treated at the MTD achieved a modified International Working Group 2006 platelet response at the end of cycle two. Of the platelet transfusion independent patients at baseline, 67% treated at the MTD became transfusion dependent during the first two cycles of treatment. Apart from lack of disease progression, our findings concur with a previously reported Phase III study (A StUdy of eltromboPag in myelodysPlastic SyndrOmes Receiving azaciTidine [SUPPORT]). We conclude that eltrombopag/azacitidine is safe in terms of conventional measures defined by adverse-event reporting. However, in light of SUPPORT and our own descriptive findings regarding efficacy, further combination studies in high-risk disease should be considered with caution.Citation
Sternberg A, Boucher R, Coulthard HC, Raghavan M, Culligan D, Jackson A, et al. Phase Ib study of eltrombopag and azacitidine in patients with high-risk myelodysplastic syndromes and related disorders (the ELASTIC study). British journal of haematology. 2022 Aug 2. PubMed PMID: 35918828. Epub 2022/08/04. eng.Journal
British Journal of HaematologyDOI
10.1111/bjh.18389PubMed ID
35918828Additional Links
https://dx.doi.org/10.1111/bjh.18389Type
ArticleLanguage
enae974a485f413a2113503eed53cd6c53
10.1111/bjh.18389