12 results on '"Park, Sophie"'
Search Results
2. A randomised phase II study of azacitidine (AZA) alone or with Lenalidomide (LEN), Valproic acid (VPA) or Idarubicin (IDA) in higher-Risk MDS or low blast AML: GFM's "pick a winner" trial, with the impact of somatic mutations.
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Adès L, Duployez N, Guerci-Bresler A, Laribi K, Peterlin P, Vey N, Thepot S, Wickenhauser S, Zerazhi H, Stamatoullas A, Wattel E, Recher C, Toma A, Dimicoli-Salazar S, Braun T, Beyne-Rauzy O, Marolleau JP, Cheze S, Park S, Cluzeau T, Nimubona S, Bordessoule D, Benramdane R, Quesnel B, Amé S, de Botton S, Chermat F, Preudhomme C, Chevret S, and Fenaux P
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- Humans, Idarubicin therapeutic use, Lenalidomide therapeutic use, Mutation, Treatment Outcome, Valproic Acid therapeutic use, Antineoplastic Combined Chemotherapy Protocols therapeutic use, Azacitidine therapeutic use, Leukemia, Myeloid, Acute drug therapy, Leukemia, Myeloid, Acute genetics
- Abstract
In order to improve the outcome observed with azacitidine (AZA) in higher-risk Myelodysplastic syndrome (MDS), its combination with other drugs in MDS must be evaluated. So far, no combination has not been shown to be more effective than AZA alone. AZA-PLUS was a phase II trial that, in a "pick a winner" approach, randomly assigned patients with higher-risk MDS, CMML and low blast count AML to: AZA; AZA plus lenalidomide; AZA plus Valproic Acid or AZA plus Idarubicin. 322 patients were included. After six cycles, 69 (21.4%) CR + PR were observed with no benefit from any combination. Median EFS and OS were 17.2 and 19.7 months in the whole cohort, respectively, with no difference across randomised arms. Infection and rates of hospitalisation during the first six cycles were higher in the AZA-LEN And AZA-IDA arm, related to increased myelosuppression. Factors associated with better response were IPSS, favourable or intermediate karyotype, haemoglobin, lower circulating blast count, fibrinogen level and lower LDH, while poorer survival was seen in therapy-related MDS and, in the case of TP53, PTPN11 or CSF3R mutation. The combinations used did not improve the outcome obtained with AZA alone. However, our "pick a winner" randomised strategy may remain useful with potentially more active drugs to be tested in combination with AZA., (© 2022 British Society for Haematology and John Wiley & Sons Ltd.)
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- 2022
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3. A phase II study of guadecitabine in higher-risk myelodysplastic syndrome and low blast count acute myeloid leukemia after azacitidine failure.
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Sébert M, Renneville A, Bally C, Peterlin P, Beyne-Rauzy O, Legros L, Gourin MP, Sanhes L, Wattel E, Gyan E, Park S, Stamatoullas A, Banos A, Laribi K, Jueliger S, Bevan L, Chermat F, Sapena R, Nibourel O, Chaffaut C, Chevret S, Preudhomme C, Adès L, and Fenaux P
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- Aged, Female, Humans, Leukemia, Myeloid, Acute mortality, Leukemia, Myeloid, Acute pathology, Male, Myelodysplastic Syndromes diagnosis, Myelodysplastic Syndromes mortality, Risk, Survival Analysis, Treatment Outcome, Azacitidine analogs & derivatives, Azacitidine therapeutic use, Leukemia, Myeloid, Acute drug therapy, Myelodysplastic Syndromes drug therapy
- Abstract
High-risk myelodysplastic syndrome/acute myeloid leukemia patients have a very poor survival after azacitidine failure. Guadecitabine (SGI-110) is a novel subcutaneous hypomethylating agent which results in extended decitabine exposure. This multicenter phase II study evaluated the efficacy and safety of guadecitabine in high-risk myelodysplastic syndrome and low blast count acute myeloid leukemia patients refractory or relapsing after azacitidine. We included 56 patients with a median age of 75 years [Interquartile Range (IQR) 69-76]. Fifty-five patients received at least one cycle of guadecitabine (60 mg/m2/d subcutaneously days 1-5 per 28-day treatment cycles), with a median of 3 cycles (range, 0-27). Eight (14.3%) patients responded, including two complete responses; median response duration was 11.5 months. Having no or few identified somatic mutations was the only factor predicting response ( P =0.035). None of the 11 patients with TP53 mutation responded. Median overall survival was 7.1 months, and 17.9 months in responders (3 of whom had overall survival >2 years). In multivariate analysis, IPSS-R (revised International Prognostic Scoring System) score other than very high ( P =0.03) primary versus secondary azacitidine failure ( P =0.01) and a high rate of demethylation in blood during the first cycle of treatment ( P =0.03) were associated with longer survival. Thus, guadecitabine can be effective, sometimes yielding relatively prolonged survival, in a small proportion of high-risk myelodysplastic syndrome/low blast count acute myeloid leukemia patients who failed azacitidine. (Trial registered a t clinicaltrials.gov identifier: 02197676 )., (Copyright© 2019 Ferrata Storti Foundation.)
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- 2019
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4. Azacitidine improves outcome in higher-risk MDS patients with chromosome 7 abnormalities: a retrospective comparison of GESMD and GFM registries.
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Díez-Campelo M, Lorenzo JI, Itzykson R, Rojas SM, Berthon C, Luño E, Beyne-Rauzy O, Perez-Oteyza J, Vey N, Bargay J, Park S, Cedena T, Bordessoule D, Muñoz JA, Gyan E, Such E, Visanica S, López-Cadenas F, de Botton S, Hernández-Rivas JM, Ame S, Stamatoullas A, Delaunay J, Salanoubat C, Isnard F, Guieze R, Pérez Guallar J, Badiella L, Sanz G, Cañizo C, and Fenaux P
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- Aged, Chromosome Aberrations, Disease-Free Survival, Female, Humans, Male, Middle Aged, Retrospective Studies, Risk Factors, Survival Rate, Azacitidine administration & dosage, Chromosomes, Human, Pair 7 genetics, Myelodysplastic Syndromes drug therapy, Myelodysplastic Syndromes genetics, Myelodysplastic Syndromes mortality, Registries
- Abstract
Treatment with azacitidine (AZA) has been suggested to be of benefit for higher-risk myelodysplastic syndrome (HR-MDS) patients with chromosome 7 abnormalities (Abn 7). This retrospective study of 235 HR-MDS patients with Abn 7 treated with AZA (n = 115) versus best supportive care (BSC; n = 120), assessed AZA treatment as a time-varying variable in multivariable analysis. A Cox Regression model with time-interaction terms of overall survival (OS) at different time points confirmed that, while chromosome 7 cytogenetic categories (complex karyotype [CK] versus non-CK) and International Prognostic Scoring System risk (high versus intermediate-2) retained poor prognosis over time, AZA treatment had a favourable impact on OS during the first 3 years of treatment compared to BSC (Hazard ratio [HR] 0·5 P < 0·001 at 1 year, 0·7 P = 0·019 at 2 years; 0·73 P = 0·029 at 3 years). This benefit was present in all chromosome 7 categories, but tended to be greater in patients with CK (risk reduction of 82%, 68% and 53% at 1, 3 and 6 months in CK patients; 79% at 1 month in non-CK patients, P < 0·05 for all). AZA also significantly improved progression-free survival (P < 0·01). This study confirms a time-dependent benefit of AZA on outcome in patients with HR-MDS and cytogenetic abnormalities involving chromosome 7, especially for those with CK., (© 2018 John Wiley & Sons Ltd.)
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- 2018
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5. A randomized phase II trial of azacitidine +/- epoetin-β in lower-risk myelodysplastic syndromes resistant to erythropoietic stimulating agents.
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Thépot S, Ben Abdelali R, Chevret S, Renneville A, Beyne-Rauzy O, Prébet T, Park S, Stamatoullas A, Guerci-Bresler A, Cheze S, Tertian G, Choufi B, Legros L, Bastié JN, Delaunay J, Chaury MP, Sanhes L, Wattel E, Dreyfus F, Vey N, Chermat F, Preudhomme C, Fenaux P, and Gardin C
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- Aged, Azacitidine administration & dosage, Biomarkers, Cytogenetic Analysis, DNA Mutational Analysis, Erythropoietin administration & dosage, Female, Hematinics therapeutic use, Humans, Male, Middle Aged, Myelodysplastic Syndromes diagnosis, Myelodysplastic Syndromes genetics, Myelodysplastic Syndromes mortality, Polymorphism, Single Nucleotide, Recombinant Proteins administration & dosage, Survival Analysis, Treatment Outcome, Antineoplastic Combined Chemotherapy Protocols therapeutic use, Azacitidine therapeutic use, Drug Resistance, Myelodysplastic Syndromes drug therapy
- Abstract
The efficacy of azacitidine in patients with anemia and with lower-risk 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)., (Copyright© Ferrata Storti Foundation.)
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- 2016
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6. Efficacy of Azacitidine in autoimmune and inflammatory disorders associated with myelodysplastic syndromes and chronic myelomonocytic leukemia.
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Fraison JB, Mekinian A, Grignano E, Kahn JE, Arlet JB, Decaux O, Denis G, Buchdahl AL, Omouri M, Maigne G, Aouba A, Leon N, Berthier S, Liozon E, Park S, Gardin C, Lortholary O, Rossignol J, Fenaux P, Fain O, and Braun T
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- Adult, Aged, Aged, 80 and over, Azacitidine adverse effects, Female, Humans, Inflammation drug therapy, Male, Middle Aged, Retrospective Studies, Autoimmune Diseases drug therapy, Azacitidine administration & dosage, Leukemia, Myelogenous, Chronic, BCR-ABL Positive drug therapy, Myelodysplastic Syndromes drug therapy
- Abstract
This retrospective study describes efficacy of Azacitidine on autoimmune disorders (AID) associated with MDS/CMML in 22 patients. Response of AID to Azacitidine was observed in 19 patients (86%). Reduction or discontinuation of steroids and/or immunosuppressive therapy (IST) was possible in 16 cases (73%). Hematologic response was seen in 55% of the patients. MDS/CMML and AID evolution was concordant in 13 cases (59%): both favorable (n=11), both unfavorable (n=2), but AID improved while MDS/CMML worsened (n=8) and vice versa (n=1). Azacitidine frequently seems effective in controlling steroid-dependent AID associated with MDS/CMML, but prospective studies are necessary to confirm those findings., (Copyright © 2016 Elsevier Ltd. All rights reserved.)
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- 2016
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7. Systemic inflammatory and autoimmune manifestations associated with myelodysplastic syndromes and chronic myelomonocytic leukaemia: a French multicentre retrospective study.
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Mekinian A, Grignano E, Braun T, Decaux O, Liozon E, Costedoat-Chalumeau N, Kahn JE, Hamidou M, Park S, Puéchal X, Toussirot E, Falgarone G, Launay D, Morel N, Trouiller S, Mathian A, Gombert B, Schoindre Y, Lioger B, De Wazieres B, Amoura Z, Buchdaul AL, Georgin-Lavialle S, Dion J, Madaule S, Raffray L, Cathebras P, Piette JC, Rose C, Ziza JM, Lortholary O, Montestruc F, Omouri M, Denis G, Rossignol J, Nimubona S, Adès L, Gardin C, Fenaux P, and Fain O
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- Aged, Antimetabolites, Antineoplastic therapeutic use, Drug Therapy, Combination, Female, Follow-Up Studies, France, Humans, Inflammation drug therapy, Inflammation etiology, Leukemia, Myelomonocytic, Chronic complications, Leukemia, Myelomonocytic, Chronic drug therapy, Male, Myelodysplastic Syndromes complications, Myelodysplastic Syndromes drug therapy, Prognosis, Retrospective Studies, Autoimmunity immunology, Azacitidine therapeutic use, Glucocorticoids therapeutic use, Inflammation immunology, Leukemia, Myelomonocytic, Chronic immunology, Myelodysplastic Syndromes immunology
- Abstract
Objective: We describe myelodysplastic syndrome (MDS)-associated systemic inflammatory and autoimmune diseases (SIADs), their treatments and outcomes and the impact of SIADs on overall survival in a French multicentre retrospective study., Methods: In this study, 123 patients with MDS and SIADs were analysed., Results: Mean age was 70 years (s.d. 13) and the male:female ratio was 2. The SIADs were systemic vasculitis in 39 (32%) cases, CTD in 31 (25%) cases, inflammatory arthritis in 28 (23%) cases, a neutrophilic disorder in 12 (10%) cases and unclassified in 13 cases (11%). The SIADs fulfilled the usual classification criteria in 75 (66%) cases, while complete criteria were not reached in 21 (19%) cases. A significant association was shown between chronic myelomonocytic leukaemia (CMML) and systemic vasculitis (P = 0.0024). One hundred and eighteen (96%) SIAD patients were treated (91% with steroids), with an 83% response to first-line treatment, including 80% for steroids alone. A second-line treatment for SIADs was required for steroid dependence or relapse in 48% of cases. The effect of MDS treatment on SIADs could be assessed in 11 patients treated with azacytidine and SIAD response was achieved in 9/11 (80%) and 6/11 (55%) patients at 3 and 6 months, respectively. Compared with 665 MDS/CMML patients without SIADs, MDS/CMML patients with SIADs were younger (P < 0.01), male (P = 0.03), less often had refractory anaemia with ring sideroblasts (P < 0.01), more often had a poor karyotype (16% vs 11%, P = 0.04) and less frequently belonged to low and intermediate-1 International Prognostic Scoring System categories, but no survival difference was seen between patients with MDS-associated SIADs and without SIADs (P = 0.5)., Conclusion: The spectrum of SIADs associated to MDS is heterogeneous, steroid sensitive, but often steroid dependent., (© The Author 2015. Published by Oxford University Press on behalf of the British Society for Rheumatology. All rights reserved. For Permissions, please email: journals.permissions@oup.com.)
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- 2016
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8. Outcome of patients with high risk Myelodysplastic Syndrome (MDS) and advanced Chronic Myelomonocytic Leukemia (CMML) treated with decitabine after azacitidine failure.
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Harel S, Cherait A, Berthon C, Willekens C, Park S, Rigal M, Brechignac S, Thépot S, Quesnel B, Gardin C, Adès L, Fenaux P, and Braun T
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- Aged, Aged, 80 and over, Decitabine, Disease Progression, Female, Humans, Leukemia, Myelomonocytic, Chronic diagnosis, Leukemia, Myelomonocytic, Chronic epidemiology, Male, Middle Aged, Myelodysplastic Syndromes diagnosis, Myelodysplastic Syndromes epidemiology, Prognosis, Retrospective Studies, Risk Factors, Treatment Failure, Treatment Outcome, Antimetabolites, Antineoplastic therapeutic use, Azacitidine analogs & derivatives, Azacitidine therapeutic use, Leukemia, Myelomonocytic, Chronic drug therapy, Myelodysplastic Syndromes drug therapy
- Abstract
Outcome of patients with high risk MDS and CMML who failed treatment with azacitidine remains poor with a median survival of 6 months, without established therapy available except allogeneic hematopoietic stem cell transplantation. The objective of our study was to evaluate efficacy of decitabine after azacitidine failure in a relatively large patient cohort based on conflicting results with 0-28% response rates (RR) in this setting in small patient series. Thirty-six consecutive high risk MDS and CMML patients who received decitabine after azacitidine failure were retrospectively reviewed. Response was based on IWG 2006 criteria for MDS and CMML with WBC<13G/l and also included for proliferative CMML the evolution of WBC, splenomegaly (SMG) and extramedullary disease (EMD). Patients received a median number of 3 (range 1-27) cycles of decitabine and 12 patients received at least 6 cycles. Seven (19.4%) patients were responders including 3 marrow CR (mCR), 2 stable disease (SD) with HI-E, 1 SD with HI-N and HI-P and 1 SD with HI-N. In a CMML patient with SD, specific skin lesions resolved with decitabine. Responses were generally short lived (2-5 months) except 1 responder currently ongoing with +11 months follow up. Two non-responders had prolonged SD (without HI) of 21 and 27 months duration respectively. Median OS from onset of decitabine was 7.3 months, without significant difference between responders and non-responders. Treatment with decitabine after azacitidine failure yielded modest ORR (19.4%) with short response duration and poor OS. Thus, use of decitabine in such patients who failed or progressed after azacitidine cannot be recommended, underscoring the need for novel strategies in this setting., (Copyright © 2015 Elsevier Ltd. All rights reserved.)
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- 2015
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9. Impact of azacitidine before allogeneic stem-cell transplantation for myelodysplastic syndromes: a study by the Société Française de Greffe de Moelle et de Thérapie-Cellulaire and the Groupe-Francophone des Myélodysplasies.
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Damaj G, Duhamel A, Robin M, Beguin Y, Michallet M, Mohty M, Vigouroux S, Bories P, Garnier A, El Cheikh J, Bulabois CE, Huynh A, Bay JO, Legrand F, Deconinck E, Fegueux N, Clement L, Dauriac C, Maillard N, Cornillon J, Ades L, Guillerm G, Schmidt-Tanguy A, Marjanovic Z, Park S, Rubio MT, Marolleau JP, Garnier F, Fenaux I, and Yakoub-Agha I
- Subjects
- Antimetabolites, Antineoplastic adverse effects, Azacitidine adverse effects, Combined Modality Therapy, Female, Humans, Induction Chemotherapy, Male, Middle Aged, Myelodysplastic Syndromes etiology, Retrospective Studies, Transplantation, Homologous methods, Treatment Outcome, Antimetabolites, Antineoplastic therapeutic use, Azacitidine therapeutic use, Hematopoietic Stem Cell Transplantation methods, Myelodysplastic Syndromes drug therapy, Myelodysplastic Syndromes surgery
- Abstract
Purpose: To investigate the impact of prior-to-transplantation azacitidine (AZA) on patient outcome after allogeneic stem-cell transplantation (alloSCT) for myelodysplastic syndrome (MDS)., Patients and Methods: Of the 265 consecutive patients who underwent alloSCT for MDS between October 2005 and December 2009, 163 had received cytoreductive treatment prior to transplantation, including induction chemotherapy (ICT) alone (ICT group; n = 98), AZA alone (AZA group; n = 48), or AZA preceded or followed by ICT (AZA-ICT group; n = 17). At diagnosis, 126 patients (77%) had an excess of marrow blasts, and 95 patients (58%) had intermediate-2 or high-risk MDS according to the International Prognostic Scoring System (IPSS). Progression to more advanced disease before alloSCT was recorded in 67 patients. Donors were sibling (n = 75) or HLA-matched unrelated (10/10; n = 88). They received blood (n = 142) or marrow (n = 21) grafts following either myeloablative (n = 33) or reduced intensity (n = 130) conditioning., Results: With a median follow-up of 38.7 months, 3-year outcomes in the AZA, ICT, and AZA-ICT groups were 55%, 48%, and 32% (P = .07) for overall survival (OS); 42%, 44%, and 29% (P = .14) for event-free survival (EFS); 40%, 37%, and 36% (P = .86) for relapse; and 19%, 20%, and 35% (P = .24) for nonrelapse mortality (NRM), respectively. Multivariate analysis confirmed the absence of statistical differences between the AZA and the ICT groups in terms of OS, EFS, relapse, and NRM., Conclusion: With the goal of downstaging underlying disease before alloSCT, AZA alone led to outcomes similar to those for standard ICT.
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- 2012
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10. The autoimmune manifestations associated with myelodysplastic syndrome respond to 5-azacytidine: a report on three cases.
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Pilorge S, Doleris LM, Dreyfus F, and Park S
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- Aged, Humans, Male, Middle Aged, Autoimmune Diseases drug therapy, Azacitidine therapeutic use, Immunologic Factors therapeutic use, Myelodysplastic Syndromes drug therapy
- Published
- 2011
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11. Increased S100A8 expression in bone marrow plasma by monocytic cells from acute myeloid leukemia patients.
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Mondet, Julie, Laurin, David, Lo Presti, Caroline, Jacob, Marie‐Christine, Meunier, Mathieu, Giraudon, Emmanuelle, Lefebvre, Christine, Berthier, Sylvie, Leer, Anne Mc, Park, Sophie, Mossuz, Pascal, and Jacob, Marie-Christine
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ACUTE myeloid leukemia ,BONE marrow ,AZACITIDINE ,PLASMA cells ,CYTARABINE ,LEUCOCYTES ,EXTRACELLULAR fluid - Abstract
Firstly, we measured S100A8 from 78 bone marrow (BM) plasmas, including 50 acute myeloid leukemia (AML) patients, myeloproliferative neoplasms (MPN), myelodysplastic syndrome (MDS), and healthy donors (HD). (D) Correlation of BM [S100A8] with the percentage of leukemic cells in BM, determined through cytology analysis in AML patients. However, no linear correlation was observed between BM [S100A8] and myeloid precursors or granulocytes in BM, ( I P i =.21, I P i =.29, respectively; Figure S1). Interestingly, the percentage of blasts in BM was negatively correlated with BM [S100A8] ( I P i < .05, R = -0.31, Figure D), suggesting that blasts were not the main source of S100A8. [Extracted from the article]
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- 2020
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12. Outcome of lower-risk patients with myelodysplastic syndromes without 5q deletion after failure of erythropoiesis-stimulating agents
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Jennifer Kaivers, Ulrich Germing, Rosa Sapena, Giovanni Cametti, Mikkael A. Sekeres, Katharina Götze, Maria Diez Campelo, Agnès Guerci-Bresler, Fabrizio Pane, Stéphane Cheze, François Dreyfus, Teresa Bernal, Enrico Balleari, David P. Steensma, Rami S. Komrokji, Pierre Fenaux, Christian Rose, Guillermo Sanz, Valeria Santini, Catharina Müller-Thomas, Marisa Calabuig, Aspasia Stamatoullas, Norbert Vey, Dario Ferrero, Alessandro Sanna, Jean Francois Hamel, Jaime Fensterl, Dominique Bordessoule, Ioannis Kotsianidis, Sophie Park, Andrea Toma, Charikleia Kelaidi, Gail J. Roboz, Fernando Ramos, Gianluca Gaidano, Sylvain Thepot, Odile Beyne-Rauzy, Pascale Cony-Makhoul, Eric Wattel, Daniela Gioia, Park, Sophie, Hamel, Jean Françoi, Toma, Andrea, Kelaidi, Charikleia, Thépot, Sylvain, Campelo, Maria Diez, Santini, Valeria, Sekeres, Mikkael A, Balleari, Enrico, Kaivers, Jennifer, Sapena, Rosa, Götze, Katharina, Müller Thomas, Catharina, Beyne Rauzy, Odile, Stamatoullas, Aspasia, Kotsianidis, Ioanni, Komrokji, Rami, Steensma, David P, Fensterl, Jaime, Roboz, Gail J, Bernal, Teresa, Ramos, Fernando, Calabuig, Marisa, Guerci Bresler, Agnè, Bordessoule, Dominique, Cony Makhoul, Pascale, Cheze, Stéphane, Wattel, Eric, Rose, Christian, Vey, Norbert, Gioia, Daniela, Ferrero, Dario, Gaidano, Gianluca, Cametti, Giovanni, Pane, Fabrizio, Sanna, Alessandro, Germing, Ulrich, Sanz, Guillermo F, Dreyfus, Françoi, and Fenaux, Pierre
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Male ,Cancer Research ,0302 clinical medicine ,Recurrence ,Risk Factors ,hemic and lymphatic diseases ,Hydroxyurea ,Cumulative incidence ,Treatment Failure ,Enzyme Inhibitors ,Lenalidomide ,Aged, 80 and over ,Cytarabine ,Anemia ,Middle Aged ,Thalidomide ,Melodysplastic syndrome ,Survival Rate ,Leukemia, Myeloid, Acute ,Oncology ,International Prognostic Scoring System ,030220 oncology & carcinogenesis ,Retreatment ,Azacitidine ,Cyclosporine ,Disease Progression ,Chromosomes, Human, Pair 5 ,Female ,Chromosome Deletion ,Erythrocyte Transfusion ,medicine.drug ,medicine.medical_specialty ,Melodysplastic syndrome, erytropoiesis stimulating agents, 5q ,erytropoiesis stimulating agents ,Decitabine ,Antineoplastic Agents ,Tretinoin ,Lower risk ,5q ,Arsenic ,03 medical and health sciences ,Internal medicine ,medicine ,Humans ,Immunologic Factors ,Survival rate ,Aged ,Antilymphocyte Serum ,Retrospective Studies ,business.industry ,Valproic Acid ,Myelodysplastic syndromes ,Retrospective cohort study ,medicine.disease ,Myelodysplastic Syndromes ,Hematinics ,Physical therapy ,business ,030215 immunology - Abstract
Purpose Most anemic patients with non-deleted 5q lower-risk myelodysplastic syndromes (MDS) are treated with erythropoiesis-stimulating agents (ESAs), with a response rate of approximately 50%. Second-line treatments, including hypomethylating agents (HMAs), lenalidomide (LEN), and investigational drugs, may be used after ESA failure in some countries, but their effect on disease progression and overall survival (OS) is unknown. Here, we analyzed outcome after ESA failure and the effect of second-line treatments. Patients and Methods We examined an international retrospective cohort of 1,698 patients with non-del(5q) lower-risk MDS treated with ESAs. Results Erythroid response to ESAs was 61.5%, and median response duration was 17 months. Of 1,147 patients experiencing ESA failure, 653 experienced primary failure and 494 experienced relapse after a response. Primary failure of ESAs was associated with a higher risk of acute myeloid leukemia (AML) progression, which did not translate into an OS difference. Of 450 patients (39%) who received second-line treatment, 194 received HMAs, 148 received LEN, and 108 received other treatments (MISC), whereas 697 received RBC transfusions only. Five-year AML cumulative incidence was 20.3%, 20.3%, and 11.3% for those receiving HMAs, LEN, and MISC, respectively ( P = .05). Five-year OS for patients receiving HMA, LEN, and MISC was 36.5%, 41.7%, and 51%, respectively ( P = .21). In a multivariable analysis adjusted for age, sex, revised International Prognostic Scoring System score, and progression at ESA failure, there was no significant OS difference among the three groups. Conclusion In this large, multicenter, retrospective cohort of patients with non-del(5q) lower-risk MDS treated with ESAs, none of the most commonly used second-line treatments (HMA and LEN) significantly improved OS. Early failure of ESAs was associated with a higher risk of AML progression.
- Published
- 2017
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