Safety and Efficacy of Eltrombopag and Romiplostim in Myelodysplastic Syndromes: A Systematic Review and Meta-Analysis

Abstract

Background and AimMany studies indicated that eltrombopag and romiplostim could improve hematopoietic function in patients with myelodysplastic syndromes (MDS), but their toxicity and efficacy were not known. This meta-analysis aimed to investigate the safety and efficacy of eltrombopag and romiplostim in MDS.MethodsA full-scale search strategy was used to search relevant published studies in PubMed, Embase, Web of Science, ClinicalTrials.gov and the Cochrane Library until January 2020 using a random-effects model and the pooled risk ratio (RR) with 95% confidence interval as the effect indicator. Statistical analyses were performed using RevMan 5.3.ResultsThis meta-analysis included eight studies comprising 1047 patients. A lower RR of overall response rate (ORR) (RR: 0.65; 95% CI, 0.47–0.9) and grade ≥3 bleeding events (RR: 0.36; 95% CI, 0.36–0.92) were observed after romiplostim and eltrombopag treatment compared with placebo. The pooled RR for the ORR and grade ≥3 bleeding events were 0.58 (95% CI: 0.41–0.83, P = 0.003) and 0.6 (95% CI: 0.37–0.96, P = 0.03) in eltrombopag, respectively. A lower ORR in intermediate- or high-risk MDS (RR: 0.63; 95% CI: 0.45–0.88, P = 0.006) was observed. No difference in mortality, serious adverse events, platelet transfusion, hematologic improvement, and AML transformation was observed.ConclusionsThrombopoietin receptor agonists (TPO-RAs) romiplostim and eltrombopag were effective in reducing bleeding events, especially grade ≥3 bleeding events. However, it might reduce the ORR of MDS, especially in eltrombopag treatment group or high-risk MDS group. Due to the limited treatment of MDS and the poor response to the drug, this may be a selection method for MDS combined with fatal bleeding, although further research is needed to confirm the effectiveness of this approach.

Eltrombopag for myelodysplastic syndromes or chronic myelomonocytic leukaemia with no excess blasts and thrombocytopenia: a French multicentre retrospective real‐life study

“…We observed disease progression in 17% of the patients (including AML transformation in four), figures similar to those observed by Oliva et al 11 in both ELT-and placebo-treated patients, and concordant with the 'natural' evolution of LR-MDS. 1 In a recent meta-analysis in MDS, 30 a potential increased risk of disease progression with TPO mimetics was likewise not confirmed. The risk of progression with ELT was found to be higher in CMML, but in a series where many patients initially had an excess of marrow blasts.…”

NCCN Guidelines® Insights: Hematopoietic Growth Factors, Version 1.2022

“…Recent data have suggested activity for the TPO-RAs lusutrombopag and eltrombopag for patients with CIT. [10][11][12] Lusutrombopag is currently FDA-approved for management of thrombocytopenia in patients with chronic liver disease who are scheduled to undergo a medical or dental procedure, and eltrombopag is approved for patients with chronic immune thrombocytopenia or severe aplastic anemia. The efficacy of lusutrombopag was assessed in an integrated analysis of data from 2 phase III trials that compared lusutrombopag versus placebo in 270 patients with chronic liver disease and hepatocellular carcinoma.…”

Treatment of inherited thrombocytopenias

“…A large and recent meta-analysis investigated the results of 8 randomized studies including 707 patients with different forms of myelodysplastic syndrome (MDS), who are at high risk of leukemic transformation. 57 The authors concluded that neither romiplostim nor eltrombopag promoted progression to leukemia (Risk Ratio: 1.08 and 1.12, respectively).…”