Does addition of erythropoiesis stimulating agents improve the outcome of higher-risk myelodysplastic syndromes treated with azacitidine?

Itzykson, Raphaël; Thépot, Sylvain; Beyne‐Rauzy, Odile; Amé, Shanti; Isnard, F; Dreyfus, François; Salanoubat, Célia; Taksin, Anne‐Laure; Chelgoum, Youcef; Berthon, Céline; Malfuson, Jean-Valère; Legros, Laurence; Vey, Norbert; Turlure, Pascal; Gardin, Claude; Boehrer, Simone; Adès, Lionel; Fenaux, Pierre

doi:10.1016/j.leukres.2011.11.019

Cited by 17 publications

(12 citation statements)

References 10 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…14 The detection of a SF3B1 mutation and the median number of RBC transfusions were significant prognostic factors of the response according to IWG 2006 criteria in our study. In the trial by Lyons et al, 8 the absence of neutropenia and thrombocytopenia, and a baseline transfusion requirement of <=2 RBC units every 8 weeks were predictive of higher RBC TI.…”

Section: © Ferrata Storti Foundationsupporting

confidence: 51%

“…lower than the 45% and 44% RBC-TI rates previously reported by other groups in unselected lower-risk MDS. 6,8,12 Explanations for those differences possibly include the fact that our patients had been selected for their resistance to ESA (which was not a prerequisite in most prior studies), and had a minimal RBC transfusion dependency of 4 units in the 8 weeks prior to the study (the median number of RBC units in the 8 weeks prior to study entry was 6 [4][5][6][7][8][9][10][11][12][13][14]). By comparison, in the Lyons et al trial 8 only 47% of patients were RBC transfusion dependent, and a lower RBC transfusion requirement (less than 2 units/8 weeks) was predictive of RBC-TI achievement with AZA (Online Supplementary Table S4).…”

Section: Discussionmentioning

confidence: 99%

“…Sylvain Thépot, 1* Raouf Ben Abdelali, 2* Sylvie Chevret, 3 Aline Renneville, 2 Odile Beyne-Rauzy, 4 Thomas Prébet, 5 Sophie Park, 6 Aspasia Stamatoullas, 7 Agnes Guerci-Bresler, 8 Stéphane Cheze, 9 Gérard Tertian, 10 Bachra Choufi, 11 Laurence Legros, 12 Jean Noel Bastié, 13 Jacques Delaunay, 14 Marie Pierre Chaury, 15 Laurence Sanhes, 16 Eric Wattel, 17 Francois Dreyfus, 6 Norbert Vey, …”

Section: A Randomized Phase II Trial Of Azacitidine +/-Epoetin-β In Lmentioning

confidence: 99%

See 2 more Smart Citations

A randomized phase II trial of azacitidine +/- epoetin- in lower-risk myelodysplastic syndromes resistant to erythropoietic stimulating agents

et al. 2016

Self Cite

View full text Add to dashboard Cite

T he efficacy of azacitidine in patients with anemia and with lowerrisk myelodysplastic syndromes, if relapsing after or resistant to erythropoietic stimulating agents, and the benefit of combining these agents to azacitidine in this setting are not well known. We prospectively compared the outcomes of patients, all of them having the characteristics of this subset of lower-risk myelodysplastic syndrome, if randomly treated with azacitidine alone or azacitidine combined with epoetin-β. High-resolution cytogenetics and gene mutation analysis were performed at entry. The primary study endpoint was the achievement of red blood cell transfusion independence after six cycles. Ninety-eight patients were randomised (49 in each arm). Median age was 72 years. In an intention to treat analysis, transfusion independence was obtained after 6 cycles in 16.3% versus 14.3% of patients in the azacitidine and azacitidine plus epoetin-β arms, respectively (P=1.00). Overall erythroid response rate (minor and major responses according to IWG 2000 criteria) was 34.7% vs. 24.5% in the azacitidine and azacitidine plus epoetin-β arms, respectively (P=0.38). Mutations of the SF3B1 gene were the only ones associated with a significant erythroid response, 29/59 (49%) versus 6/27 (22%) in SF3B1 mutated and unmutated patients, respectively, P=0.02. Detection of at least one "epigenetic mutation" and of an abnormal single nucleotide polymorphism array profile were the only factors associated with significantly poorer overall survival by multivariate analysis. The transfusion independence rate observed with azacitidine in this lower-risk population, but resistant to erythropoietic stimulating agents, was lower than expected, with no observed benefit of added epoetin, (clinicaltrials.gov identifier: 01015352).

show abstract

Section: © Ferrata Storti Foundationsupporting

confidence: 51%

Section: Discussionmentioning

confidence: 99%

Section: A Randomized Phase II Trial Of Azacitidine +/-Epoetin-β In Lmentioning

confidence: 99%

See 1 more Smart Citation

A randomized phase II trial of azacitidine +/- epoetin- in lower-risk myelodysplastic syndromes resistant to erythropoietic stimulating agents

et al. 2016

Self Cite

View full text Add to dashboard Cite

show abstract

“…In a retrospective French analysis of 32 HR-MDS who received a concurrent combination regimen of azacitidine with ESA, 44 and 48% reached HI-E and transfusion-independence, respectively, in comparison to 29% ( P = 0.07) and 20% ( P = 0.01) in a cohort of azacitidine-treated HR-MDS patients who did not receive ESA therapy [46]. Moreover, the median OS was 19.6 vs. 11.9 months ( P = 0.04), respectively, and ESA use was independently associated with improved overall survival ( P = 0.03).…”

Section: Combination Strategiesmentioning

confidence: 99%

Beyond hypomethylating agents failure in patients with myelodysplastic syndromes

Zeidan

Kharfan‐Dabaja

Komrokji

2014

Current Opinion in Hematology

View full text Add to dashboard Cite

Purpose of review Although hypomethylating agents (HMAs) significantly improve outcomes in myelodysplastic syndromes (MDS), only half the patients achieve objective responses, and most responders lose response within 1–2 years. Azacitidine prolongs survival by a median of only 9.5 months. Failure of HMA therapy is associated with a very dismal prognosis. Therefore, novel therapeutic approaches are clearly needed. Recent findings The sequential use of the alternative HMA after failure of first line HMA is associated with modest efficacy. The improved understanding of the biologic underpinnings of the disease have opened the door to study investigational agents that target disrupted molecular pathways critical to the pathogenesis of MDS. Combination treatment strategies using an azacitidine backbone are demonstrating promising early results. Expanding the applicability of allogeneic stem cell transplantation (alloSCT), the only curative modality, by reducing toxicity and relapse rates is another area of active research. Summary Sequential switching to the alternative HMA, clinical trials of novel targeted therapies, azacitidine-based combination therapeutic strategies, and improvements in the alloSCT platform are the main directions in improving outcomes of MDS post HMA failure.

show abstract

“…Although both the use of ESA [5] (to reduce the high burden of transfusion requirement in MDS patients [6]) and azacitidine [7,8] (to contain or reverse the natural progression of disease) are well established, very few studies have explored the therapeutic role exerted by the association of azacitidine with EPO in the setting of higher-risk MDS. A retrospective French study that included 32 higher-risk MDS patients, who concomitantly received ESA and azacitidine found that the addition of ESA to the hypomethylating therapy significantly improved overall survival independent of azacitidine schedule and duration [9]. These findings may reflect synergistic effects exerted by two agents or their separate actions on distinct mechanisms and/or components of MDS.…”

mentioning

confidence: 99%

273 Regaining the Response to Erythropoietin Following Azacitidine in Chronic Myelomonocytic Leukemia Previously Evolved From Refractory Anemia

Niscola¹,

Andrea²,

Marco³

et al. 2015

Leukemia Research

View full text Add to dashboard Cite

Does addition of erythropoiesis stimulating agents improve the outcome of higher-risk myelodysplastic syndromes treated with azacitidine?

Cited by 17 publications

References 10 publications

A randomized phase II trial of azacitidine +/- epoetin- in lower-risk myelodysplastic syndromes resistant to erythropoietic stimulating agents

A randomized phase II trial of azacitidine +/- epoetin- in lower-risk myelodysplastic syndromes resistant to erythropoietic stimulating agents

Beyond hypomethylating agents failure in patients with myelodysplastic syndromes

273 Regaining the Response to Erythropoietin Following Azacitidine in Chronic Myelomonocytic Leukemia Previously Evolved From Refractory Anemia

Contact Info

Product

Resources

About