Thrombopoietin mimetics for patients with myelodysplastic syndromes

Dodillet, Helga; Kreuzer, Karl‐Anton; Monsef, Ina; Skoetz, Nicole

doi:10.1002/14651858.cd009883.pub2

Cited by 18 publications

(14 citation statements)

References 64 publications

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“…Furthermore, bleeding events were defined as number of patients with bleeding, not adjusted for exposure per patient month, so there was non-significant. These results were consistent with previous meta-analysis that when adjusted, there was significantly RR of bleeding (35).…”

Section: Discussionsupporting

confidence: 93%

“…In addition, this meta-analysis included less than 10 trials, so the significance of publication bias is limited. A meta-analysis involving 746 patients found no significant differences in mortality (RR: 0.97; 95% CI: 0.73-1.27) and progression to AML (RR: 1.02; 95% CI: 0.59-1.77, P = 0.03), but a lower risk of bleeding events (RR: 0.92; 95% CI: 0.86-0.99) in MDS treated with TPO-RAs (35), which were also consistent with the results of the present meta-analysis.…”

Section: Discussionmentioning

confidence: 90%

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

Meng

Chen

et al. 2020

Front. Oncol.

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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.

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Section: Discussionsupporting

confidence: 93%

Section: Discussionmentioning

confidence: 90%

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

Meng

Chen

et al. 2020

Front. Oncol.

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“…In a meta-analysis, Dodillet et al found that treatment with TPO-RA resulted in a lower number of MDS patients suffering from bleeding events. Although some studies have highlighted the potential risk of TPO-RA in accelerating leukemic progression or an increase of blasts in MDS patients, 28-30 more recent data from randomized controlled trials 31-33 and meta-analyses 34 , 35 did not seem to confirm this. Moreover, preclinical studies found that eltrombopag could inhibit leukemic cell growth in tissue culture and in animal models of leukemia.…”

Section: Discussionmentioning

confidence: 99%

Clinical spectrum, outcome and management of immune thrombocytopenia associated with myelodysplastic syndromes and chronic myelomonocytic leukemia

et al. 2021

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Myelodysplastic syndromes (MDS) and chronic myelomonocytic leukemia (CMML) are associated with systemic inflammatory or autoimmune diseases in 10-20 % of cases. Among them, immune thrombocytopenia (ITP) has been reported but large studies assessing this association are missing. Whether such patients have a particular phenotype and require particular management is unclear. This study analyzes the clinical spectrum, outcome and therapeutic management of patients with ITP associated with MDS or CMML, in comparison (i) to patients with primary ITP without MDS/CMML and (ii) to patients with MDS/CMML without ITP. Forty-one MDS/CMML-associated ITP patients were included, with chronic ITP in 26 (63%) patients, low-risk myelodysplasia in 30 (73%) patients and CMML in 24 (59%) patients. An associated autoimmune disease was noted in 10 (24%) patients. In comparison to primary ITP patients, MDS/CMML-associated ITP patients had a higher occurrence of severe bleeding despite similar platelet counts at diagnosis. First-line treatment consisted of glucocorticoids (98%) and intravenous immunoglobulin (IVIg) (56%). Response achievement with IVIg was more frequent in primary ITP than in MDS/CMML-associated ITP patients. Response rates to second-line therapies were not statistically different between primary ITP and MDS/CMMLassociated ITP patients. Ten percent (n=4) of patients with MDS/CMML-associated ITP had multirefractory ITP versus none in primary ITP controls. After a median follow-up of 60 months, there was no difference in overall survival between MDS/CMML-associated ITP and primary ITP patients. Leukemia-free-survival was significantly better in MDS/CMMLassociated ITP patients than in MDS/CMML without ITP MDS/CMML-associated ITP have a particular outcome with more severe bleeding and multirefractory profile than primary ITP, similar response profile to primary ITP therapy except for IVIg, and less progression toward acute myeloid leukemia than MDS/CMML without ITP.

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“…A recent meta-analysis further supports these conclusions, stating that no comparison between both agents have been performed, and further research is mandatory to answer the open question. 52 …”

Section: Discussionmentioning

confidence: 99%

Thrombocytopenia in Patients With Myelodysplastic Syndromes - Still an Unsolved Problem

Basood

Oster

Mittelman

2018

Mediterr J Hematol Infect Dis

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The myelodysplastic syndromes (MDS) are a group of clonal bone marrow (BM) stem cell disorders, characterized by ineffective hematopoiesis, peripheral cytopenias, and hematologic cellular dysfunction, as well as potential transformation to acute leukemia.Thrombocytopenia is common in MDS and is associated with bleeding complications, occasionally life-threatening. Low platelet count (PLT), as well declining PLT also serves as a prognostic marker. Understanding thrombopoiesis led to the cloning of thrombopoietin, resulting in the development of platelet stimulating agents, thrombomimetics, romiplostim and eltrombopag.Both agents have been shown to increase PLT, decrease the need for platelet transfusions and reduce the number of bleeding episodes, with a reasonable tolerance. They are already approved for immune thrombocytopenia and thrombocytopenia related to liver disease.Romiplostim and eltrombopag have proven efficacy in lower- and higher-risk MDS with thrombocytopenia, as monotherapy, as well as a part of a combination, either with lenalidomide, and mainly combined with hypomethylating agents. However, safety concerns have been raised: while several trials have been completed with no evidence of disease progression, others have been early terminated due to an increased number of BM blasts and possible leukemic transformation in treated-patients. The jury is still out regarding this safety concern, although recent publications are more encouraging.

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Thrombopoietin mimetics for patients with myelodysplastic syndromes

Abstract: Analysis 1.33. Comparison 1 Thrombopoietin mimetics versus placebo, Outcome 33 Serious adverse events -di erent types of additional agents..

Cited by 18 publications

References 64 publications

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

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

Clinical spectrum, outcome and management of immune thrombocytopenia associated with myelodysplastic syndromes and chronic myelomonocytic leukemia

Thrombocytopenia in Patients With Myelodysplastic Syndromes - Still an Unsolved Problem

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