Skip to main content
Top

18-04-2024 | Myelodysplastic Syndrome

Treatment of Myelodysplastic Syndromes for Older Patients: Current State of Science, Challenges, and Opportunities

Authors: Tariq Kewan, Maximillian Stahl, Jan Philipp Bewersdorf, Amer M. Zeidan

Published in: Current Hematologic Malignancy Reports

Login to get access

Abstract

Purpose of Review

Myelodysplastic syndromes/neoplasms (MDS) represent a diverse group of pathologically distinct diseases with varying prognoses and risks of leukemia progression. This review aims to discuss current treatment options for elderly patients with MDS, focusing on patients ineligible for intensive chemotherapy or allogenic hematopoietic stem cell transplantation (HSCT). The challenges associated with treatment in this population and emerging therapeutic prospects are also explored.

Recent Findings

Recent advancements in molecular diagnostics have enhanced risk stratification by incorporating genetic mutations, notably through the molecular International Prognostic Scoring System (IPSS-M). Lower-risk MDS (LR-MDS) treatment ranges from observation to supportive measures and erythropoiesis-stimulating agents (ESAs), with emerging therapies like luspatercept showing promise. High-risk MDS (HR-MDS) is treated with hypomethylating agents (HMAs) or allogenic HSCT, but outcomes remain poor.

Summary

Elderly MDS patients, often diagnosed after 70, pose challenges in treatment decision-making. The IPSS-M aids risk stratification, guiding therapeutic choices. For LR-MDS, supportive care, ESAs, and novel agents like luspatercept are considered. Treatment of HR-MDS involves HMAs or allogenic HSCT. Emerging treatments, including oral HMAs and novel agents targeting FLT3, and IDH 1/2 mutations, show promise. Future research should refine treatment strategies for this elderly population focusing on quality-of-life improvement.
Literature
3.
go back to reference Shallis RM, Ahmad R, Zeidan AM. The genetic and molecular pathogenesis of myelodysplastic syndromes. Eur J Haematol. 2018;101(3):260–71.PubMedCrossRef Shallis RM, Ahmad R, Zeidan AM. The genetic and molecular pathogenesis of myelodysplastic syndromes. Eur J Haematol. 2018;101(3):260–71.PubMedCrossRef
7.
go back to reference Jansen AJ, Essink-Bot ML, Beckers EA, Hop WC, Schipperus MR, Van Rhenen DJ. Quality of life measurement in patients with transfusion-dependent myelodysplastic syndromes. Br J Haematol. 2003;121(2):270–4.PubMedCrossRef Jansen AJ, Essink-Bot ML, Beckers EA, Hop WC, Schipperus MR, Van Rhenen DJ. Quality of life measurement in patients with transfusion-dependent myelodysplastic syndromes. Br J Haematol. 2003;121(2):270–4.PubMedCrossRef
8.
go back to reference Greenberg P, Cox C, LeBeau MM, Fenaux P, Morel P, Sanz G, et al. International scoring system for evaluating prognosis in myelodysplastic syndromes. Blood. 1997;89(6):2079–88.PubMedCrossRef Greenberg P, Cox C, LeBeau MM, Fenaux P, Morel P, Sanz G, et al. International scoring system for evaluating prognosis in myelodysplastic syndromes. Blood. 1997;89(6):2079–88.PubMedCrossRef
9.
go back to reference Greenberg PL, Tuechler H, Schanz J, Sanz G, Garcia-Manero G, Sole F, et al. Revised international prognostic scoring system for myelodysplastic syndromes. Blood. 2012;120(12):2454–65.PubMedPubMedCentralCrossRef Greenberg PL, Tuechler H, Schanz J, Sanz G, Garcia-Manero G, Sole F, et al. Revised international prognostic scoring system for myelodysplastic syndromes. Blood. 2012;120(12):2454–65.PubMedPubMedCentralCrossRef
10.••
go back to reference Bernard E, Nannya Y, Hasserjian RP, Devlin SM, Tuechler H, Medina-Martinez JS, et al. Implications of TP53 allelic state for genome stability, clinical presentation and outcomes in myelodysplastic syndromes. Nat Med. 2020;26(10):1549–56. The study highlights the prognostic impact of TP53 mutation on clinical outcomes among patients with MDS. Bernard E, Nannya Y, Hasserjian RP, Devlin SM, Tuechler H, Medina-Martinez JS, et al. Implications of TP53 allelic state for genome stability, clinical presentation and outcomes in myelodysplastic syndromes. Nat Med. 2020;26(10):1549–56. The study highlights the prognostic impact of TP53 mutation on clinical outcomes among patients with MDS.
11.
go back to reference Bahaj W, Kewan T, Gurnari C, Durmaz A, Ponvilawan B, Pandit I, Kubota Y, Ogbue OD, Zawit M, Madanat Y, Bat T, Balasubramanian SK, Awada H, Ahmed R, Mori M, Meggendorfer M, Haferlach T, Visconte V, Maciejewski JP. Novel scheme for defining the clinical implications of TP53 mutations in myeloid neoplasia. J Hematol Oncol. 2023;16(1):91. https://doi.org/10.1186/s13045-023-01480-y. Bahaj W, Kewan T, Gurnari C, Durmaz A, Ponvilawan B, Pandit I, Kubota Y, Ogbue OD, Zawit M, Madanat Y, Bat T, Balasubramanian SK, Awada H, Ahmed R, Mori M, Meggendorfer M, Haferlach T, Visconte V, Maciejewski JP. Novel scheme for defining the clinical implications of TP53 mutations in myeloid neoplasia. J Hematol Oncol. 2023;16(1):91. https://​doi.​org/​10.​1186/​s13045-023-01480-y.
12.
go back to reference Malcovati L, Hellstrom-Lindberg E, Bowen D, Ades L, Cermak J, Del Canizo C, et al. Diagnosis and treatment of primary myelodysplastic syndromes in adults: recommendations from the European LeukemiaNet. Blood. 2013;122(17):2943–64.PubMedPubMedCentralCrossRef Malcovati L, Hellstrom-Lindberg E, Bowen D, Ades L, Cermak J, Del Canizo C, et al. Diagnosis and treatment of primary myelodysplastic syndromes in adults: recommendations from the European LeukemiaNet. Blood. 2013;122(17):2943–64.PubMedPubMedCentralCrossRef
13.
go back to reference Tobiasson M, Kittang AO. Treatment of myelodysplastic syndrome in the era of next-generation sequencing. J Intern Med. 2019;286(1):41–62.PubMedCrossRef Tobiasson M, Kittang AO. Treatment of myelodysplastic syndrome in the era of next-generation sequencing. J Intern Med. 2019;286(1):41–62.PubMedCrossRef
14.•
go back to reference Fenaux P, Haase D, Santini V, Sanz GF, Platzbecker U, Mey U, et al. Myelodysplastic syndromes: ESMO clinical practice guidelines for diagnosis, treatment and follow-up(dagger☆). Ann Oncol. 2021;32(2):142–56. The article provide guidelines for the management and diagnosis of MDS. Fenaux P, Haase D, Santini V, Sanz GF, Platzbecker U, Mey U, et al. Myelodysplastic syndromes: ESMO clinical practice guidelines for diagnosis, treatment and follow-up(dagger☆). Ann Oncol. 2021;32(2):142–56. The article provide guidelines for the management and diagnosis of MDS.
15.
go back to reference Sekeres MA, Taylor J. Diagnosis and treatment of myelodysplastic syndromes: a review. JAMA. 2022;328(9):872–80.PubMedCrossRef Sekeres MA, Taylor J. Diagnosis and treatment of myelodysplastic syndromes: a review. JAMA. 2022;328(9):872–80.PubMedCrossRef
16.
go back to reference Bernard E, Tuechler H, Greenberg PL, Hasserjian RP, Ossa JEA, Nannya Y, et al. Molecular international prognostic scoring system for myelodysplastic syndromes. NEJM Evid. 2022;1(7):EVIDoa2200008.PubMedCrossRef Bernard E, Tuechler H, Greenberg PL, Hasserjian RP, Ossa JEA, Nannya Y, et al. Molecular international prognostic scoring system for myelodysplastic syndromes. NEJM Evid. 2022;1(7):EVIDoa2200008.PubMedCrossRef
17.
go back to reference Bersanelli M, Travaglino E, Meggendorfer M, Matteuzzi T, Sala C, Mosca E, et al. Classification and personalized prognostic assessment on the basis of clinical and genomic features in myelodysplastic syndromes. J Clin Oncol. 2021;39(11):1223–33.PubMedPubMedCentralCrossRef Bersanelli M, Travaglino E, Meggendorfer M, Matteuzzi T, Sala C, Mosca E, et al. Classification and personalized prognostic assessment on the basis of clinical and genomic features in myelodysplastic syndromes. J Clin Oncol. 2021;39(11):1223–33.PubMedPubMedCentralCrossRef
18.
go back to reference Zeidan AM, Shallis RM, Wang R, Davidoff A, Ma X. Epidemiology of myelodysplastic syndromes: why characterizing the beast is a prerequisite to taming it. Blood Rev. 2019;34:1–15.PubMedCrossRef Zeidan AM, Shallis RM, Wang R, Davidoff A, Ma X. Epidemiology of myelodysplastic syndromes: why characterizing the beast is a prerequisite to taming it. Blood Rev. 2019;34:1–15.PubMedCrossRef
19.
go back to reference Hamaker ME, Stauder R, van Munster BC. Exclusion of older patients from ongoing clinical trials for hematological malignancies: an evaluation of the National Institutes of Health Clinical Trial Registry. Oncologist. 2014;19(10):1069–75.PubMedPubMedCentralCrossRef Hamaker ME, Stauder R, van Munster BC. Exclusion of older patients from ongoing clinical trials for hematological malignancies: an evaluation of the National Institutes of Health Clinical Trial Registry. Oncologist. 2014;19(10):1069–75.PubMedPubMedCentralCrossRef
20.••
go back to reference Shallis RM, Zeidan AM. Management of the older patient with myelodysplastic syndrome. Drugs Aging. 2021;38(9):751–67. The study highlights the unique aspect of MDS management in elderly patients, the current study include a more recent review/changes.PubMedCrossRef Shallis RM, Zeidan AM. Management of the older patient with myelodysplastic syndrome. Drugs Aging. 2021;38(9):751–67. The study highlights the unique aspect of MDS management in elderly patients, the current study include a more recent review/changes.PubMedCrossRef
22.
go back to reference Pfeilstocker M, Tuechler H, Sanz G, Schanz J, Garcia-Manero G, Sole F, et al. Time-dependent changes in mortality and transformation risk in MDS. Blood. 2016;128(7):902–10.PubMedPubMedCentralCrossRef Pfeilstocker M, Tuechler H, Sanz G, Schanz J, Garcia-Manero G, Sole F, et al. Time-dependent changes in mortality and transformation risk in MDS. Blood. 2016;128(7):902–10.PubMedPubMedCentralCrossRef
23.
go back to reference Aguirre LE, Al Ali N, Sallman DA, Ball S, Jain AG, Chan O, Tinsley-Vance SM, Kuykendall A, Sweet K, Lancet JE, Padron E, Komrokji RS. Assessment and validation of the molecular international prognostic scoring system for myelodysplastic syndromes. Leukemia. 2023;37(7):1530-1539. https://doi.org/10.1038/s41375-023-01910-3. Aguirre LE, Al Ali N, Sallman DA, Ball S, Jain AG, Chan O, Tinsley-Vance SM, Kuykendall A, Sweet K, Lancet JE, Padron E, Komrokji RS. Assessment and validation of the molecular international prognostic scoring system for myelodysplastic syndromes. Leukemia. 2023;37(7):1530-1539. https://​doi.​org/​10.​1038/​s41375-023-01910-3.
24.
go back to reference Kewan T, Bahaj W, Durmaz A, Aly M, Ogbue OD, Carraway HE, et al. Validation of the Molecular International Prognostic Scoring System in patients with myelodysplastic syndromes. Blood. 2023;141(14):1768–72.PubMedPubMedCentralCrossRef Kewan T, Bahaj W, Durmaz A, Aly M, Ogbue OD, Carraway HE, et al. Validation of the Molecular International Prognostic Scoring System in patients with myelodysplastic syndromes. Blood. 2023;141(14):1768–72.PubMedPubMedCentralCrossRef
25.
go back to reference Sauta E, Robin M, Bersanelli M, Travaglino E, Meggendorfer M, Zhao LP, Caballero Berrocal JC, Sala C, Maggioni G, Bernardi M, Di Grazia C, Vago L, Rivoli G, Borin L, D'Amico S, Tentori CA, Ubezio M, Campagna A, Russo A, Mannina D, Lanino L, Chiusolo P, Giaccone L, Voso MT, Riva M, Oliva EN, Zampini M, Riva E, Nibourel O, Bicchieri M, Bolli N, Rambaldi A, Passamonti F, Savevski V, Santoro A, Germing U, Kordasti S, Santini V, Diez-Campelo M, Sanz G, Sole F, Kern W, Platzbecker U, Ades L, Fenaux P, Haferlach T, Castellani G, Della Porta MG. Real-World Validation of Molecular International Prognostic Scoring System for Myelodysplastic Syndromes. J Clin Oncol. 2023;41(15):2827-2842. https://doi.org/10.1200/JCO.22.01784. Sauta E, Robin M, Bersanelli M, Travaglino E, Meggendorfer M, Zhao LP, Caballero Berrocal JC, Sala C, Maggioni G, Bernardi M, Di Grazia C, Vago L, Rivoli G, Borin L, D'Amico S, Tentori CA, Ubezio M, Campagna A, Russo A, Mannina D, Lanino L, Chiusolo P, Giaccone L, Voso MT, Riva M, Oliva EN, Zampini M, Riva E, Nibourel O, Bicchieri M, Bolli N, Rambaldi A, Passamonti F, Savevski V, Santoro A, Germing U, Kordasti S, Santini V, Diez-Campelo M, Sanz G, Sole F, Kern W, Platzbecker U, Ades L, Fenaux P, Haferlach T, Castellani G, Della Porta MG. Real-World Validation of Molecular International Prognostic Scoring System for Myelodysplastic Syndromes. J Clin Oncol. 2023;41(15):2827-2842. https://​doi.​org/​10.​1200/​JCO.​22.​01784.
26.
go back to reference Wall SA, Huang Y, Keiter A, Funderburg A, Kloock C, Yuhasz N, Gure TR, Folefac E, Stevens E, Presley CJ, Williams NO, Krok-Schoen JL, Naughton MJ, Rosko AE. Integration of a geriatric assessment with intervention in the care of older adults with hematologic malignancies. Front Oncol. 2021;11:775050. https://doi.org/10.3389/fonc.2021.775050 Wall SA, Huang Y, Keiter A, Funderburg A, Kloock C, Yuhasz N, Gure TR, Folefac E, Stevens E, Presley CJ, Williams NO, Krok-Schoen JL, Naughton MJ, Rosko AE. Integration of a geriatric assessment with intervention in the care of older adults with hematologic malignancies. Front Oncol. 2021;11:775050. https://​doi.​org/​10.​3389/​fonc.​2021.​775050
28.
go back to reference Bejar R, Stevenson K, Abdel-Wahab O, Galili N, Nilsson B, Garcia-Manero G, et al. Clinical effect of point mutations in myelodysplastic syndromes. N Engl J Med. 2011;364(26):2496–506.PubMedPubMedCentralCrossRef Bejar R, Stevenson K, Abdel-Wahab O, Galili N, Nilsson B, Garcia-Manero G, et al. Clinical effect of point mutations in myelodysplastic syndromes. N Engl J Med. 2011;364(26):2496–506.PubMedPubMedCentralCrossRef
29.
go back to reference Papaemmanuil E, Gerstung M, Malcovati L, Tauro S, Gundem G, Van Loo P, et al. Clinical and biological implications of driver mutations in myelodysplastic syndromes. Blood. 2013;122(22):3616–27.PubMedPubMedCentralCrossRef Papaemmanuil E, Gerstung M, Malcovati L, Tauro S, Gundem G, Van Loo P, et al. Clinical and biological implications of driver mutations in myelodysplastic syndromes. Blood. 2013;122(22):3616–27.PubMedPubMedCentralCrossRef
30.
go back to reference Culleton BF, Manns BJ, Zhang J, Tonelli M, Klarenbach S, Hemmelgarn BR. Impact of anemia on hospitalization and mortality in older adults. Blood. 2006;107(10):3841–6.PubMedCrossRef Culleton BF, Manns BJ, Zhang J, Tonelli M, Klarenbach S, Hemmelgarn BR. Impact of anemia on hospitalization and mortality in older adults. Blood. 2006;107(10):3841–6.PubMedCrossRef
31.
go back to reference Zakai NA, Katz R, Hirsch C, Shlipak MG, Chaves PH, Newman AB, et al. A prospective study of anemia status, hemoglobin concentration, and mortality in an elderly cohort: the Cardiovascular Health Study. Arch Intern Med. 2005;165(19):2214–20.PubMedCrossRef Zakai NA, Katz R, Hirsch C, Shlipak MG, Chaves PH, Newman AB, et al. A prospective study of anemia status, hemoglobin concentration, and mortality in an elderly cohort: the Cardiovascular Health Study. Arch Intern Med. 2005;165(19):2214–20.PubMedCrossRef
32.
go back to reference Denny SD, Kuchibhatla MN, Cohen HJ. Impact of anemia on mortality, cognition, and function in community-dwelling elderly. Am J Med. 2006;119(4):327–34.PubMedCrossRef Denny SD, Kuchibhatla MN, Cohen HJ. Impact of anemia on mortality, cognition, and function in community-dwelling elderly. Am J Med. 2006;119(4):327–34.PubMedCrossRef
34.
go back to reference Fenaux P, Santini V, Spiriti MAA, Giagounidis A, Schlag R, Radinoff A, et al. A phase 3 randomized, placebo-controlled study assessing the efficacy and safety of epoetin-alpha in anemic patients with low-risk MDS. Leukemia. 2018;32(12):2648–58.PubMedPubMedCentralCrossRef Fenaux P, Santini V, Spiriti MAA, Giagounidis A, Schlag R, Radinoff A, et al. A phase 3 randomized, placebo-controlled study assessing the efficacy and safety of epoetin-alpha in anemic patients with low-risk MDS. Leukemia. 2018;32(12):2648–58.PubMedPubMedCentralCrossRef
35.
go back to reference Platzbecker U, Symeonidis A, Oliva EN, Goede JS, Delforge M, Mayer J, et al. A phase 3 randomized placebo-controlled trial of darbepoetin alfa in patients with anemia and lower-risk myelodysplastic syndromes. Leukemia. 2017;31(9):1944–50.PubMedPubMedCentralCrossRef Platzbecker U, Symeonidis A, Oliva EN, Goede JS, Delforge M, Mayer J, et al. A phase 3 randomized placebo-controlled trial of darbepoetin alfa in patients with anemia and lower-risk myelodysplastic syndromes. Leukemia. 2017;31(9):1944–50.PubMedPubMedCentralCrossRef
36.
go back to reference Gabrilove J, Paquette R, Lyons RM, Mushtaq C, Sekeres MA, Tomita D, et al. Phase 2, single-arm trial to evaluate the effectiveness of darbepoetin alfa for correcting anaemia in patients with myelodysplastic syndromes. Br J Haematol. 2008;142(3):379–93.PubMedPubMedCentralCrossRef Gabrilove J, Paquette R, Lyons RM, Mushtaq C, Sekeres MA, Tomita D, et al. Phase 2, single-arm trial to evaluate the effectiveness of darbepoetin alfa for correcting anaemia in patients with myelodysplastic syndromes. Br J Haematol. 2008;142(3):379–93.PubMedPubMedCentralCrossRef
37.
go back to reference Jadersten M, Montgomery SM, Dybedal I, Porwit-MacDonald A, Hellstrom-Lindberg E. Long-term outcome of treatment of anemia in MDS with erythropoietin and G-CSF. Blood. 2005;106(3):803–11.PubMedCrossRef Jadersten M, Montgomery SM, Dybedal I, Porwit-MacDonald A, Hellstrom-Lindberg E. Long-term outcome of treatment of anemia in MDS with erythropoietin and G-CSF. Blood. 2005;106(3):803–11.PubMedCrossRef
38.
go back to reference Hellstrom-Lindberg E, Negrin R, Stein R, Krantz S, Lindberg G, Vardiman J, et al. Erythroid response to treatment with G-CSF plus erythropoietin for the anaemia of patients with myelodysplastic syndromes: proposal for a predictive model. Br J Haematol. 1997;99(2):344–51.PubMedCrossRef Hellstrom-Lindberg E, Negrin R, Stein R, Krantz S, Lindberg G, Vardiman J, et al. Erythroid response to treatment with G-CSF plus erythropoietin for the anaemia of patients with myelodysplastic syndromes: proposal for a predictive model. Br J Haematol. 1997;99(2):344–51.PubMedCrossRef
39.
go back to reference Hellstrom-Lindberg E, Gulbrandsen N, Lindberg G, Ahlgren T, Dahl IM, Dybedal I, et al. A validated decision model for treating the anaemia of myelodysplastic syndromes with erythropoietin + granulocyte colony-stimulating factor: significant effects on quality of life. Br J Haematol. 2003;120(6):1037–46.PubMedCrossRef Hellstrom-Lindberg E, Gulbrandsen N, Lindberg G, Ahlgren T, Dahl IM, Dybedal I, et al. A validated decision model for treating the anaemia of myelodysplastic syndromes with erythropoietin + granulocyte colony-stimulating factor: significant effects on quality of life. Br J Haematol. 2003;120(6):1037–46.PubMedCrossRef
40.
go back to reference Fenaux P, Platzbecker U, Mufti GJ, Garcia-Manero G, Buckstein R, Santini V, et al. Luspatercept in patients with lower-risk myelodysplastic syndromes. N Engl J Med. 2020;382(2):140–51.PubMedCrossRef Fenaux P, Platzbecker U, Mufti GJ, Garcia-Manero G, Buckstein R, Santini V, et al. Luspatercept in patients with lower-risk myelodysplastic syndromes. N Engl J Med. 2020;382(2):140–51.PubMedCrossRef
41.
go back to reference Suragani RN, Cadena SM, Cawley SM, Sako D, Mitchell D, Li R, et al. Transforming growth factor-beta superfamily ligand trap ACE-536 corrects anemia by promoting late-stage erythropoiesis. Nat Med. 2014;20(4):408–14.PubMedCrossRef Suragani RN, Cadena SM, Cawley SM, Sako D, Mitchell D, Li R, et al. Transforming growth factor-beta superfamily ligand trap ACE-536 corrects anemia by promoting late-stage erythropoiesis. Nat Med. 2014;20(4):408–14.PubMedCrossRef
42.
go back to reference Platzbecker U, Germing U, Gotze KS, Kiewe P, Mayer K, Chromik J, et al. Luspatercept for the treatment of anaemia in patients with lower-risk myelodysplastic syndromes (PACE-MDS): a multicentre, open-label phase 2 dose-finding study with long-term extension study. Lancet Oncol. 2017;18(10):1338–47.PubMedCrossRef Platzbecker U, Germing U, Gotze KS, Kiewe P, Mayer K, Chromik J, et al. Luspatercept for the treatment of anaemia in patients with lower-risk myelodysplastic syndromes (PACE-MDS): a multicentre, open-label phase 2 dose-finding study with long-term extension study. Lancet Oncol. 2017;18(10):1338–47.PubMedCrossRef
43.
go back to reference Platzbecker U, Gotze KS, Kiewe P, Germing U, Mayer K, Radsak M, et al. Long-term efficacy and safety of luspatercept for anemia treatment in patients with lower-risk myelodysplastic syndromes: the Phase II PACE-MDS Study. J Clin Oncol. 2022;40(33):3800–7.PubMedPubMedCentralCrossRef Platzbecker U, Gotze KS, Kiewe P, Germing U, Mayer K, Radsak M, et al. Long-term efficacy and safety of luspatercept for anemia treatment in patients with lower-risk myelodysplastic syndromes: the Phase II PACE-MDS Study. J Clin Oncol. 2022;40(33):3800–7.PubMedPubMedCentralCrossRef
44.
go back to reference Zeidan AM, Platzbecker U, Garcia-Manero G, Sekeres MA, Fenaux P, DeZern AE, et al. Longer-term benefit of luspatercept in transfusion-dependent lower-risk myelodysplastic syndromes with ring sideroblasts. Blood. 2022;140(20):2170–4.PubMedPubMedCentralCrossRef Zeidan AM, Platzbecker U, Garcia-Manero G, Sekeres MA, Fenaux P, DeZern AE, et al. Longer-term benefit of luspatercept in transfusion-dependent lower-risk myelodysplastic syndromes with ring sideroblasts. Blood. 2022;140(20):2170–4.PubMedPubMedCentralCrossRef
45.•
go back to reference Platzbecker U, Della Porta MG, Santini V, Zeidan AM, Komrokji RS, Shortt J, et al. Efficacy and safety of luspatercept versus epoetin alfa in erythropoiesis-stimulating agent-naive, transfusion-dependent, lower-risk myelodysplastic syndromes (COMMANDS): interim analysis of a phase 3, open-label, randomised controlled trial. Lancet. 2023;402(10399):373–85. In the interim analysis of the COMMANDS trial, luspatercept improved the rate at which red blood cell transfusion independence and increased hemoglobin were achieved compared to epoetin alfa in ESA-naive patients with low-risk MDS.PubMedCrossRef Platzbecker U, Della Porta MG, Santini V, Zeidan AM, Komrokji RS, Shortt J, et al. Efficacy and safety of luspatercept versus epoetin alfa in erythropoiesis-stimulating agent-naive, transfusion-dependent, lower-risk myelodysplastic syndromes (COMMANDS): interim analysis of a phase 3, open-label, randomised controlled trial. Lancet. 2023;402(10399):373–85. In the interim analysis of the COMMANDS trial, luspatercept improved the rate at which red blood cell transfusion independence and increased hemoglobin were achieved compared to epoetin alfa in ESA-naive patients with low-risk MDS.PubMedCrossRef
46.
go back to reference Steensma DP, Fenaux P, Van Eygen K, Raza A, Santini V, Germing U, et al. Imetelstat achieves meaningful and durable transfusion independence in high transfusion-burden patients with lower-risk myelodysplastic syndromes in a phase II study. J Clin Oncol. 2021;39(1):48–56.PubMedCrossRef Steensma DP, Fenaux P, Van Eygen K, Raza A, Santini V, Germing U, et al. Imetelstat achieves meaningful and durable transfusion independence in high transfusion-burden patients with lower-risk myelodysplastic syndromes in a phase II study. J Clin Oncol. 2021;39(1):48–56.PubMedCrossRef
47.
go back to reference Uwe Platzbecker RSK, Fenaux Pierre, Zeidan Amer M, Sekeres Mikkael A, Savona Michael Robert, Madanat Yazan F, Santini Valeria, Van Eygen Koen, Raza Azra, Germing Ulrich, Berry Tymara, Dougherty Souria, Shah Sheetal, Sun Libo, Huang Fei, Feller Faye, Wan Ying, Ikin Annat, Sherman Laurie. Imetelstat achieved prolonged, continuous transfusion independence (TI) in patients with heavily transfused non-Del(5q) lower-risk myelodysplastic syndrome (LR-MDS) relapsed/refractory (R/R) to erythropoiesis stimulating agents (ESAs) within the IMerge Phase 2 Study. Blood. 2022;140:1106–8.CrossRef Uwe Platzbecker RSK, Fenaux Pierre, Zeidan Amer M, Sekeres Mikkael A, Savona Michael Robert, Madanat Yazan F, Santini Valeria, Van Eygen Koen, Raza Azra, Germing Ulrich, Berry Tymara, Dougherty Souria, Shah Sheetal, Sun Libo, Huang Fei, Feller Faye, Wan Ying, Ikin Annat, Sherman Laurie. Imetelstat achieved prolonged, continuous transfusion independence (TI) in patients with heavily transfused non-Del(5q) lower-risk myelodysplastic syndrome (LR-MDS) relapsed/refractory (R/R) to erythropoiesis stimulating agents (ESAs) within the IMerge Phase 2 Study. Blood. 2022;140:1106–8.CrossRef
49.
go back to reference Amer Methqal Zeidan UP, Santini Valeria, Fenaux Pierre, Sekeres Mikkael A, Savona Michael R, Madanat Yazan F, Diez-Campelo Maria, Valcarcel David, Illmer Thomas, Jonasova Anna, Belohlavkova Petra, Sherman Laurie Jill, Berry Tymara, Dougherty Souria, Shah Sheetal, Sun Libo, Wan Ying, Huang Fei, Komrokji Rami S. IMerge: results from a phase 3, randomized, double-blind, placebo-controlled study of imetelstat in patients (pts) with heavily transfusion dependent (TD) non-del(5q) lower-risk myelodysplastic syndromes (LR-MDS) relapsed/refractory (R/R) to erythropoiesis stimulating agents (ESA). J Clin Oncol. 2023;41:7004.CrossRef Amer Methqal Zeidan UP, Santini Valeria, Fenaux Pierre, Sekeres Mikkael A, Savona Michael R, Madanat Yazan F, Diez-Campelo Maria, Valcarcel David, Illmer Thomas, Jonasova Anna, Belohlavkova Petra, Sherman Laurie Jill, Berry Tymara, Dougherty Souria, Shah Sheetal, Sun Libo, Wan Ying, Huang Fei, Komrokji Rami S. IMerge: results from a phase 3, randomized, double-blind, placebo-controlled study of imetelstat in patients (pts) with heavily transfusion dependent (TD) non-del(5q) lower-risk myelodysplastic syndromes (LR-MDS) relapsed/refractory (R/R) to erythropoiesis stimulating agents (ESA). J Clin Oncol. 2023;41:7004.CrossRef
50.
go back to reference List AF, Sun Z, Verma A, Bennett JM, Komrokji RS, McGraw K, et al. Lenalidomide-epoetin alfa versus lenalidomide monotherapy in myelodysplastic syndromes refractory to recombinant erythropoietin. J Clin Oncol. 2021;39(9):1001–9.PubMedPubMedCentralCrossRef List AF, Sun Z, Verma A, Bennett JM, Komrokji RS, McGraw K, et al. Lenalidomide-epoetin alfa versus lenalidomide monotherapy in myelodysplastic syndromes refractory to recombinant erythropoietin. J Clin Oncol. 2021;39(9):1001–9.PubMedPubMedCentralCrossRef
51.
go back to reference List A, Dewald G, Bennett J, Giagounidis A, Raza A, Feldman E, et al. Lenalidomide in the myelodysplastic syndrome with chromosome 5q deletion. N Engl J Med. 2006;355(14):1456–65.PubMedCrossRef List A, Dewald G, Bennett J, Giagounidis A, Raza A, Feldman E, et al. Lenalidomide in the myelodysplastic syndrome with chromosome 5q deletion. N Engl J Med. 2006;355(14):1456–65.PubMedCrossRef
52.
go back to reference List A, Kurtin S, Roe DJ, Buresh A, Mahadevan D, Fuchs D, et al. Efficacy of lenalidomide in myelodysplastic syndromes. N Engl J Med. 2005;352(6):549–57.PubMedCrossRef List A, Kurtin S, Roe DJ, Buresh A, Mahadevan D, Fuchs D, et al. Efficacy of lenalidomide in myelodysplastic syndromes. N Engl J Med. 2005;352(6):549–57.PubMedCrossRef
53.
go back to reference Raza A, Reeves JA, Feldman EJ, Dewald GW, Bennett JM, Deeg HJ, et al. Phase 2 study of lenalidomide in transfusion-dependent, low-risk, and intermediate-1 risk myelodysplastic syndromes with karyotypes other than deletion 5q. Blood. 2008;111(1):86–93.PubMedCrossRef Raza A, Reeves JA, Feldman EJ, Dewald GW, Bennett JM, Deeg HJ, et al. Phase 2 study of lenalidomide in transfusion-dependent, low-risk, and intermediate-1 risk myelodysplastic syndromes with karyotypes other than deletion 5q. Blood. 2008;111(1):86–93.PubMedCrossRef
54.
go back to reference Sperling AS, Guerra VA, Kennedy JA, Yan Y, Hsu JI, Wang F, et al. Lenalidomide promotes the development of TP53-mutated therapy-related myeloid neoplasms. Blood. 2022;140(16):1753–63.PubMedPubMedCentralCrossRef Sperling AS, Guerra VA, Kennedy JA, Yan Y, Hsu JI, Wang F, et al. Lenalidomide promotes the development of TP53-mutated therapy-related myeloid neoplasms. Blood. 2022;140(16):1753–63.PubMedPubMedCentralCrossRef
55.
go back to reference Félix López Cadenas EL, González Teresa, Xicoy Blanca, Sánchez-García Joaquín, Coll Rosa, Slama Bohrane, Hernández-Rivas José Ángel, Thepot Sylvain, Bernal Teresa, Guerci-Bresler Agnès, Sanz Guillermo, Bargay Joan, Amigo Maria Luz, De Paz Raquel, Arias Claude Preudhomme, Giagounidis Aristoteles, Platzbecker Uwe, Wickenhauser Stefan, Goetze Katharina S, Arar Ali, Hernández Jesús M, Rivas Sofía M, Castelló Toribio, Fenaux Pierre, Del Cañizo Consuelo, Diez-Campelo Maria. Evaluation of lenalidomide (LEN) vs placebo in non-transfusion dependent low risk Del(5q) MDS patients. Final results of Sintra-REV phase III international multicenter clinical trial. Blood. 2022;140:1109–11.CrossRef Félix López Cadenas EL, González Teresa, Xicoy Blanca, Sánchez-García Joaquín, Coll Rosa, Slama Bohrane, Hernández-Rivas José Ángel, Thepot Sylvain, Bernal Teresa, Guerci-Bresler Agnès, Sanz Guillermo, Bargay Joan, Amigo Maria Luz, De Paz Raquel, Arias Claude Preudhomme, Giagounidis Aristoteles, Platzbecker Uwe, Wickenhauser Stefan, Goetze Katharina S, Arar Ali, Hernández Jesús M, Rivas Sofía M, Castelló Toribio, Fenaux Pierre, Del Cañizo Consuelo, Diez-Campelo Maria. Evaluation of lenalidomide (LEN) vs placebo in non-transfusion dependent low risk Del(5q) MDS patients. Final results of Sintra-REV phase III international multicenter clinical trial. Blood. 2022;140:1109–11.CrossRef
56.
go back to reference Zeidan AM, Griffiths EA. To chelate or not to chelate in MDS: that is the question! Blood Rev. 2018;32(5):368–77.PubMedCrossRef Zeidan AM, Griffiths EA. To chelate or not to chelate in MDS: that is the question! Blood Rev. 2018;32(5):368–77.PubMedCrossRef
57.
go back to reference Zeidan AM, Hendrick F, Friedmann E, Baer MR, Gore SD, Sasane M, et al. Deferasirox therapy is associated with reduced mortality risk in a medicare population with myelodysplastic syndromes. J Comp Eff Res. 2015;4(4):327–40.PubMedPubMedCentralCrossRef Zeidan AM, Hendrick F, Friedmann E, Baer MR, Gore SD, Sasane M, et al. Deferasirox therapy is associated with reduced mortality risk in a medicare population with myelodysplastic syndromes. J Comp Eff Res. 2015;4(4):327–40.PubMedPubMedCentralCrossRef
58.
go back to reference Angelucci E, Li J, Greenberg P, Wu D, Hou M, Montano Figueroa EH, et al. Iron chelation in transfusion-dependent patients with low- to intermediate-1-risk myelodysplastic syndromes: a randomized trial. Ann Intern Med. 2020;172(8):513–22.PubMedCrossRef Angelucci E, Li J, Greenberg P, Wu D, Hou M, Montano Figueroa EH, et al. Iron chelation in transfusion-dependent patients with low- to intermediate-1-risk myelodysplastic syndromes: a randomized trial. Ann Intern Med. 2020;172(8):513–22.PubMedCrossRef
59.
go back to reference Kantarjian HM, Giles FJ, Greenberg PL, Paquette RL, Wang ES, Gabrilove JL, et al. Phase 2 study of romiplostim in patients with low- or intermediate-risk myelodysplastic syndrome receiving azacitidine therapy. Blood. 2010;116(17):3163–70.PubMedPubMedCentralCrossRef Kantarjian HM, Giles FJ, Greenberg PL, Paquette RL, Wang ES, Gabrilove JL, et al. Phase 2 study of romiplostim in patients with low- or intermediate-risk myelodysplastic syndrome receiving azacitidine therapy. Blood. 2010;116(17):3163–70.PubMedPubMedCentralCrossRef
60.
go back to reference Oliva EN, Alati C, Santini V, Poloni A, Molteni A, Niscola P, et al. Eltrombopag versus placebo for low-risk myelodysplastic syndromes with thrombocytopenia (EQoL-MDS): phase 1 results of a single-blind, randomised, controlled, phase 2 superiority trial. Lancet Haematol. 2017;4(3):e127–36.PubMedCrossRef Oliva EN, Alati C, Santini V, Poloni A, Molteni A, Niscola P, et al. Eltrombopag versus placebo for low-risk myelodysplastic syndromes with thrombocytopenia (EQoL-MDS): phase 1 results of a single-blind, randomised, controlled, phase 2 superiority trial. Lancet Haematol. 2017;4(3):e127–36.PubMedCrossRef
61.
go back to reference Platzbecker U, Sekeres MA, Kantarjian H, Giagounidis A, Mufti GJ, Jia C, et al. Relationship of different platelet response criteria and patient outcomes in a romiplostim myelodysplastic syndromes trial. Leukemia. 2014;28(12):2418–21.PubMedPubMedCentralCrossRef Platzbecker U, Sekeres MA, Kantarjian H, Giagounidis A, Mufti GJ, Jia C, et al. Relationship of different platelet response criteria and patient outcomes in a romiplostim myelodysplastic syndromes trial. Leukemia. 2014;28(12):2418–21.PubMedPubMedCentralCrossRef
62.
go back to reference Kantarjian HM, Fenaux P, Sekeres MA, Szer J, Platzbecker U, Kuendgen A, et al. Long-term follow-up for up to 5 years on the risk of leukaemic progression in thrombocytopenic patients with lower-risk myelodysplastic syndromes treated with romiplostim or placebo in a randomised double-blind trial. Lancet Haematol. 2018;5(3):e117–26.PubMedCrossRef Kantarjian HM, Fenaux P, Sekeres MA, Szer J, Platzbecker U, Kuendgen A, et al. Long-term follow-up for up to 5 years on the risk of leukaemic progression in thrombocytopenic patients with lower-risk myelodysplastic syndromes treated with romiplostim or placebo in a randomised double-blind trial. Lancet Haematol. 2018;5(3):e117–26.PubMedCrossRef
63.
go back to reference Dickinson M, Cherif H, Fenaux P, Mittelman M, Verma A, Portella MSO, et al. Azacitidine with or without eltrombopag for first-line treatment of intermediate- or high-risk MDS with thrombocytopenia. Blood. 2018;132(25):2629–38.PubMedPubMedCentralCrossRef Dickinson M, Cherif H, Fenaux P, Mittelman M, Verma A, Portella MSO, et al. Azacitidine with or without eltrombopag for first-line treatment of intermediate- or high-risk MDS with thrombocytopenia. Blood. 2018;132(25):2629–38.PubMedPubMedCentralCrossRef
64.
go back to reference Oliva EN, Riva M, Niscola P, Santini V, Breccia M, Giai V, et al. Eltrombopag for low-risk myelodysplastic syndromes with thrombocytopenia: interim results of a phase ii, randomized, placebo-controlled clinical trial (EQOL-MDS). J Clin Oncol. 2023;41(28):4486–96.PubMedPubMedCentralCrossRef Oliva EN, Riva M, Niscola P, Santini V, Breccia M, Giai V, et al. Eltrombopag for low-risk myelodysplastic syndromes with thrombocytopenia: interim results of a phase ii, randomized, placebo-controlled clinical trial (EQOL-MDS). J Clin Oncol. 2023;41(28):4486–96.PubMedPubMedCentralCrossRef
65.
go back to reference Lindquist KJ, Danese MD, Mikhael J, Knopf KB, Griffiths RI. Health care utilization and mortality among elderly patients with myelodysplastic syndromes. Ann Oncol. 2011;22(5):1181–8.PubMedCrossRef Lindquist KJ, Danese MD, Mikhael J, Knopf KB, Griffiths RI. Health care utilization and mortality among elderly patients with myelodysplastic syndromes. Ann Oncol. 2011;22(5):1181–8.PubMedCrossRef
66.
go back to reference Bodey GP, Buckley M, Sathe YS, Freireich EJ. Quantitative relationships between circulating leukocytes and infection in patients with acute leukemia. Ann Intern Med. 1966;64(2):328–40.PubMedCrossRef Bodey GP, Buckley M, Sathe YS, Freireich EJ. Quantitative relationships between circulating leukocytes and infection in patients with acute leukemia. Ann Intern Med. 1966;64(2):328–40.PubMedCrossRef
67.
go back to reference Mikulska M, Averbuch D, Tissot F, Cordonnier C, Akova M, Calandra T, et al. Fluoroquinolone prophylaxis in haematological cancer patients with neutropenia: ECIL critical appraisal of previous guidelines. J Infect. 2018;76(1):20–37.PubMedCrossRef Mikulska M, Averbuch D, Tissot F, Cordonnier C, Akova M, Calandra T, et al. Fluoroquinolone prophylaxis in haematological cancer patients with neutropenia: ECIL critical appraisal of previous guidelines. J Infect. 2018;76(1):20–37.PubMedCrossRef
68.
go back to reference Ruping MJ, Vehreschild JJ, Cornely OA. Primary antifungal prophylaxis in acute myeloblastic leukemia and myelodysplastic syndrome–still an open question? Leuk Lymphoma. 2010;51(1):20–6.PubMedCrossRef Ruping MJ, Vehreschild JJ, Cornely OA. Primary antifungal prophylaxis in acute myeloblastic leukemia and myelodysplastic syndrome–still an open question? Leuk Lymphoma. 2010;51(1):20–6.PubMedCrossRef
69.
go back to reference Halpern AB, Lyman GH, Walsh TJ, Kontoyiannis DP, Walter RB. Primary antifungal prophylaxis during curative-intent therapy for acute myeloid leukemia. Blood. 2015;126(26):2790–7.PubMedPubMedCentralCrossRef Halpern AB, Lyman GH, Walsh TJ, Kontoyiannis DP, Walter RB. Primary antifungal prophylaxis during curative-intent therapy for acute myeloid leukemia. Blood. 2015;126(26):2790–7.PubMedPubMedCentralCrossRef
70.
go back to reference Antin JH, Smith BR, Holmes W, Rosenthal DS. Phase I/II study of recombinant human granulocyte-macrophage colony-stimulating factor in aplastic anemia and myelodysplastic syndrome. Blood. 1988;72(2):705–13.PubMedCrossRef Antin JH, Smith BR, Holmes W, Rosenthal DS. Phase I/II study of recombinant human granulocyte-macrophage colony-stimulating factor in aplastic anemia and myelodysplastic syndrome. Blood. 1988;72(2):705–13.PubMedCrossRef
71.
go back to reference Casadevall N, Durieux P, Dubois S, Hemery F, Lepage E, Quarre MC, et al. Health, economic, and quality-of-life effects of erythropoietin and granulocyte colony-stimulating factor for the treatment of myelodysplastic syndromes: a randomized, controlled trial. Blood. 2004;104(2):321–7.PubMedCrossRef Casadevall N, Durieux P, Dubois S, Hemery F, Lepage E, Quarre MC, et al. Health, economic, and quality-of-life effects of erythropoietin and granulocyte colony-stimulating factor for the treatment of myelodysplastic syndromes: a randomized, controlled trial. Blood. 2004;104(2):321–7.PubMedCrossRef
72.
go back to reference Vadhan-Raj S, Keating M, LeMaistre A, Hittelman WN, McCredie K, Trujillo JM, et al. Effects of recombinant human granulocyte-macrophage colony-stimulating factor in patients with myelodysplastic syndromes. N Engl J Med. 1987;317(25):1545–52.PubMedCrossRef Vadhan-Raj S, Keating M, LeMaistre A, Hittelman WN, McCredie K, Trujillo JM, et al. Effects of recombinant human granulocyte-macrophage colony-stimulating factor in patients with myelodysplastic syndromes. N Engl J Med. 1987;317(25):1545–52.PubMedCrossRef
73.
go back to reference Komrokji R, Swern AS, Grinblatt D, Lyons RM, Tobiasson M, Silverman LR, et al. Azacitidine in lower-risk myelodysplastic syndromes: a meta-analysis of data from prospective studies. Oncologist. 2018;23(2):159–70.PubMedCrossRef Komrokji R, Swern AS, Grinblatt D, Lyons RM, Tobiasson M, Silverman LR, et al. Azacitidine in lower-risk myelodysplastic syndromes: a meta-analysis of data from prospective studies. Oncologist. 2018;23(2):159–70.PubMedCrossRef
74.
go back to reference Jabbour E, Short NJ, Montalban-Bravo G, Huang X, Bueso-Ramos C, Qiao W, et al. Randomized phase 2 study of low-dose decitabine vs low-dose azacitidine in lower-risk MDS and MDS/MPN. Blood. 2017;130(13):1514–22.PubMedPubMedCentralCrossRef Jabbour E, Short NJ, Montalban-Bravo G, Huang X, Bueso-Ramos C, Qiao W, et al. Randomized phase 2 study of low-dose decitabine vs low-dose azacitidine in lower-risk MDS and MDS/MPN. Blood. 2017;130(13):1514–22.PubMedPubMedCentralCrossRef
75.
go back to reference Sasaki K, Jabbour E, Montalban-Bravo G, Darbaniyan F, Do KA, Class C, Short NJ, Kanagal-Shamana R, Kadia T, Borthakur G, Pemmaraju N, Cortes J, Ravandi F, Alvarado Y, Chien K, Komrokji R, Sekeres MA, Steensma DP, DeZern A, Roboz G, Soltysiak K, Yang H, Kantarjian HM, Garcia-Manero G. Low-Dose Decitabine versus Low-Dose Azacitidine in Lower-Risk MDS. NEJM Evid. 2022;1(10):EVIDoa2200034. https://doi.org/10.1056/EVIDoa2200034. Sasaki K, Jabbour E, Montalban-Bravo G, Darbaniyan F, Do KA, Class C, Short NJ, Kanagal-Shamana R, Kadia T, Borthakur G, Pemmaraju N, Cortes J, Ravandi F, Alvarado Y, Chien K, Komrokji R, Sekeres MA, Steensma DP, DeZern A, Roboz G, Soltysiak K, Yang H, Kantarjian HM, Garcia-Manero G. Low-Dose Decitabine versus Low-Dose Azacitidine in Lower-Risk MDS. NEJM Evid. 2022;1(10):EVIDoa2200034. https://​doi.​org/​10.​1056/​EVIDoa2200034.
76.
go back to reference Zeidan AM, Davidoff AJ, Long JB, Hu X, Wang R, Ma X, et al. Comparative clinical effectiveness of azacitidine versus decitabine in older patients with myelodysplastic syndromes. Br J Haematol. 2016;175(5):829–40.PubMedCrossRef Zeidan AM, Davidoff AJ, Long JB, Hu X, Wang R, Ma X, et al. Comparative clinical effectiveness of azacitidine versus decitabine in older patients with myelodysplastic syndromes. Br J Haematol. 2016;175(5):829–40.PubMedCrossRef
77.
go back to reference Garcia-Manero G, Santini V, Almeida A, Platzbecker U, Jonasova A, Silverman LR, et al. Phase III, randomized, placebo-controlled trial of CC-486 (oral azacitidine) in patients with lower-risk myelodysplastic syndromes. J Clin Oncol. 2021;39(13):1426–36.PubMedPubMedCentralCrossRef Garcia-Manero G, Santini V, Almeida A, Platzbecker U, Jonasova A, Silverman LR, et al. Phase III, randomized, placebo-controlled trial of CC-486 (oral azacitidine) in patients with lower-risk myelodysplastic syndromes. J Clin Oncol. 2021;39(13):1426–36.PubMedPubMedCentralCrossRef
78.
go back to reference Fenaux P, Mufti GJ, Hellstrom-Lindberg E, Santini V, Finelli C, Giagounidis A, et al. Efficacy of azacitidine compared with that of conventional care regimens in the treatment of higher-risk myelodysplastic syndromes: a randomised, open-label, phase III study. Lancet Oncol. 2009;10(3):223–32.PubMedPubMedCentralCrossRef Fenaux P, Mufti GJ, Hellstrom-Lindberg E, Santini V, Finelli C, Giagounidis A, et al. Efficacy of azacitidine compared with that of conventional care regimens in the treatment of higher-risk myelodysplastic syndromes: a randomised, open-label, phase III study. Lancet Oncol. 2009;10(3):223–32.PubMedPubMedCentralCrossRef
79.
go back to reference Ghorab A, Al-Kali A, Elliot M, Gangat N, Alkhateeb H, Shah M, et al. Clinical outcome of myelodysplastic syndrome progressing on hypomethylating agents with evolving frontline therapies: continued challenges and unmet needs. Blood Cancer J. 2022;12(6):93.PubMedPubMedCentralCrossRef Ghorab A, Al-Kali A, Elliot M, Gangat N, Alkhateeb H, Shah M, et al. Clinical outcome of myelodysplastic syndrome progressing on hypomethylating agents with evolving frontline therapies: continued challenges and unmet needs. Blood Cancer J. 2022;12(6):93.PubMedPubMedCentralCrossRef
80.
go back to reference Zeidan AM, Stahl M, Hu X, Wang R, Huntington SF, Podoltsev NA, et al. Long-term survival of older patients with MDS treated with HMA therapy without subsequent stem cell transplantation. Blood. 2018;131(7):818–21.PubMedPubMedCentralCrossRef Zeidan AM, Stahl M, Hu X, Wang R, Huntington SF, Podoltsev NA, et al. Long-term survival of older patients with MDS treated with HMA therapy without subsequent stem cell transplantation. Blood. 2018;131(7):818–21.PubMedPubMedCentralCrossRef
81.
go back to reference Garcia-Manero G, Griffiths EA, Steensma DP, Roboz GJ, Wells R, McCloskey J, et al. Oral cedazuridine/decitabine for MDS and CMML: a phase 2 pharmacokinetic/pharmacodynamic randomized crossover study. Blood. 2020;136(6):674–83.PubMedPubMedCentralCrossRef Garcia-Manero G, Griffiths EA, Steensma DP, Roboz GJ, Wells R, McCloskey J, et al. Oral cedazuridine/decitabine for MDS and CMML: a phase 2 pharmacokinetic/pharmacodynamic randomized crossover study. Blood. 2020;136(6):674–83.PubMedPubMedCentralCrossRef
82.
go back to reference Wei AH, Dohner H, Pocock C, Montesinos P, Afanasyev B, Dombret H, et al. Oral azacitidine maintenance therapy for acute myeloid leukemia in first remission. N Engl J Med. 2020;383(26):2526–37.PubMedCrossRef Wei AH, Dohner H, Pocock C, Montesinos P, Afanasyev B, Dombret H, et al. Oral azacitidine maintenance therapy for acute myeloid leukemia in first remission. N Engl J Med. 2020;383(26):2526–37.PubMedCrossRef
83.
go back to reference Koreth J, Pidala J, Perez WS, Deeg HJ, Garcia-Manero G, Malcovati L, et al. Role of reduced-intensity conditioning allogeneic hematopoietic stem-cell transplantation in older patients with de novo myelodysplastic syndromes: an international collaborative decision analysis. J Clin Oncol. 2013;31(21):2662–70.PubMedPubMedCentralCrossRef Koreth J, Pidala J, Perez WS, Deeg HJ, Garcia-Manero G, Malcovati L, et al. Role of reduced-intensity conditioning allogeneic hematopoietic stem-cell transplantation in older patients with de novo myelodysplastic syndromes: an international collaborative decision analysis. J Clin Oncol. 2013;31(21):2662–70.PubMedPubMedCentralCrossRef
84.
go back to reference Pohlen M, Groth C, Sauer T, Gorlich D, Mesters R, Schliemann C, et al. Outcome of allogeneic stem cell transplantation for AML and myelodysplastic syndrome in elderly patients (⩾60 years). Bone Marrow Transplant. 2016;51(11):1441–8.PubMedCrossRef Pohlen M, Groth C, Sauer T, Gorlich D, Mesters R, Schliemann C, et al. Outcome of allogeneic stem cell transplantation for AML and myelodysplastic syndrome in elderly patients (⩾60 years). Bone Marrow Transplant. 2016;51(11):1441–8.PubMedCrossRef
85.
go back to reference Atallah E, Logan B, Chen M, Cutler C, Deeg J, Jacoby M, et al. Comparison of patient age groups in transplantation for myelodysplastic syndrome: the medicare coverage with evidence development study. JAMA Oncol. 2020;6(4):486–93.PubMedCrossRef Atallah E, Logan B, Chen M, Cutler C, Deeg J, Jacoby M, et al. Comparison of patient age groups in transplantation for myelodysplastic syndrome: the medicare coverage with evidence development study. JAMA Oncol. 2020;6(4):486–93.PubMedCrossRef
86.
go back to reference Kroger N. Allogeneic stem cell transplantation for elderly patients with myelodysplastic syndrome. Blood. 2012;119(24):5632–9.PubMedCrossRef Kroger N. Allogeneic stem cell transplantation for elderly patients with myelodysplastic syndrome. Blood. 2012;119(24):5632–9.PubMedCrossRef
87.
go back to reference Yahng SA, Kim M, Kim TM, Jeon YW, Yoon JH, Shin SH, et al. Better transplant outcome with pre-transplant marrow response after hypomethylating treatment in higher-risk MDS with excess blasts. Oncotarget. 2017;8(7):12342–54.PubMedCrossRef Yahng SA, Kim M, Kim TM, Jeon YW, Yoon JH, Shin SH, et al. Better transplant outcome with pre-transplant marrow response after hypomethylating treatment in higher-risk MDS with excess blasts. Oncotarget. 2017;8(7):12342–54.PubMedCrossRef
88.
go back to reference Pierre Peterlin PT, Chevallier Patrice, Gourin Marie-Pierre, Dumas Pierre-Yves, Thepot Sylvain, Berceanu Anna, Park Sophie, Hospital Marie Anne, Cluzeau Thomas, Diaz Jose Miguel Torregrosa, Devron Louis, Chevret Sylvie, Bene Marie C, Le Bris Yannick, Sapena Rosa, Chermat Fatiha, Dimicoli-Salazar Sophie, Fenaux Pierre. CPX 351 as first line treatment in higher risk MDS. A phase II trial by the GFM. Blood. 2021;138:243.CrossRef Pierre Peterlin PT, Chevallier Patrice, Gourin Marie-Pierre, Dumas Pierre-Yves, Thepot Sylvain, Berceanu Anna, Park Sophie, Hospital Marie Anne, Cluzeau Thomas, Diaz Jose Miguel Torregrosa, Devron Louis, Chevret Sylvie, Bene Marie C, Le Bris Yannick, Sapena Rosa, Chermat Fatiha, Dimicoli-Salazar Sophie, Fenaux Pierre. CPX 351 as first line treatment in higher risk MDS. A phase II trial by the GFM. Blood. 2021;138:243.CrossRef
89.
go back to reference Kroger N, Sockel K, Wolschke C, Bethge W, Schlenk RF, Wolf D, et al. Comparison between 5-azacytidine treatment and allogeneic stem-cell transplantation in elderly patients with advanced MDS according to donor availability (VidazaAllo Study). J Clin Oncol. 2021;39(30):3318–27.PubMedCrossRef Kroger N, Sockel K, Wolschke C, Bethge W, Schlenk RF, Wolf D, et al. Comparison between 5-azacytidine treatment and allogeneic stem-cell transplantation in elderly patients with advanced MDS according to donor availability (VidazaAllo Study). J Clin Oncol. 2021;39(30):3318–27.PubMedCrossRef
90.
go back to reference Wei AH, Strickland SA Jr, Hou JZ, Fiedler W, Lin TL, Walter RB, et al. Venetoclax combined with low-dose cytarabine for previously untreated patients with acute myeloid leukemia: results from a phase Ib/II study. J Clin Oncol. 2019;37(15):1277–84.PubMedPubMedCentralCrossRef Wei AH, Strickland SA Jr, Hou JZ, Fiedler W, Lin TL, Walter RB, et al. Venetoclax combined with low-dose cytarabine for previously untreated patients with acute myeloid leukemia: results from a phase Ib/II study. J Clin Oncol. 2019;37(15):1277–84.PubMedPubMedCentralCrossRef
91.
go back to reference DiNardo CD, Jonas BA, Pullarkat V, Thirman MJ, Garcia JS, Wei AH, et al. Azacitidine and venetoclax in previously untreated acute myeloid leukemia. N Engl J Med. 2020;383(7):617–29.PubMedCrossRef DiNardo CD, Jonas BA, Pullarkat V, Thirman MJ, Garcia JS, Wei AH, et al. Azacitidine and venetoclax in previously untreated acute myeloid leukemia. N Engl J Med. 2020;383(7):617–29.PubMedCrossRef
92.
go back to reference Wei AH, Montesinos P, Ivanov V, DiNardo CD, Novak J, Laribi K, et al. Venetoclax plus LDAC for newly diagnosed AML ineligible for intensive chemotherapy: a phase 3 randomized placebo-controlled trial. Blood. 2020;135(24):2137–45.PubMedPubMedCentralCrossRef Wei AH, Montesinos P, Ivanov V, DiNardo CD, Novak J, Laribi K, et al. Venetoclax plus LDAC for newly diagnosed AML ineligible for intensive chemotherapy: a phase 3 randomized placebo-controlled trial. Blood. 2020;135(24):2137–45.PubMedPubMedCentralCrossRef
93.
go back to reference Andrew H, Wei JSG, Borate Uma, Fong Chun Yew, Baer Maria R, Nolte Florian, Peterlin Pierre, Jurcic Joseph G, Garcia-Manero Guillermo, Hong Wan-Jen, Platzbecker Uwe, Odenike Olatoyosi, Dunbar Martin, Zhou Ying, Harb Jason, Tanwani Poonam, Wolff Johannes E, Jacoby Meagan. A phase 1b study evaluating the safety and efficacy of venetoclax in combination with azacitidine in treatment-naïve patients with higher-risk myelodysplastic syndrome. Blood. 2019;134:568.CrossRef Andrew H, Wei JSG, Borate Uma, Fong Chun Yew, Baer Maria R, Nolte Florian, Peterlin Pierre, Jurcic Joseph G, Garcia-Manero Guillermo, Hong Wan-Jen, Platzbecker Uwe, Odenike Olatoyosi, Dunbar Martin, Zhou Ying, Harb Jason, Tanwani Poonam, Wolff Johannes E, Jacoby Meagan. A phase 1b study evaluating the safety and efficacy of venetoclax in combination with azacitidine in treatment-naïve patients with higher-risk myelodysplastic syndrome. Blood. 2019;134:568.CrossRef
94.
go back to reference Zeidan AM, Borate U, Pollyea DA, Brunner AM, Roncolato F, Garcia JS, et al. A phase 1b study of venetoclax and azacitidine combination in patients with relapsed or refractory myelodysplastic syndromes. Am J Hematol. 2023;98(2):272–81.PubMedCrossRef Zeidan AM, Borate U, Pollyea DA, Brunner AM, Roncolato F, Garcia JS, et al. A phase 1b study of venetoclax and azacitidine combination in patients with relapsed or refractory myelodysplastic syndromes. Am J Hematol. 2023;98(2):272–81.PubMedCrossRef
95.
97.
go back to reference Sallman DA, Al Malki MM, Asch AS, Wang ES, Jurcic JG, Bradley TJ, Flinn IW, Pollyea DA, Kambhampati S, Tanaka TN, Zeidner JF, Garcia-Manero G, Jeyakumar D, Komrokji R, Lancet J, Kantarjian HM, Gu L, Zhang Y, Tan A, Chao M, O'Hear C, Ramsingh G, Lal I, Vyas P, Daver NG. Magrolimab in combination with azacitidine in patients with higher-risk myelodysplastic syndromes: final results of a phase Ib study. J Clin Oncol. 2023;41(15):2815–2826. https://doi.org/10.1200/JCO.22.01794. Sallman DA, Al Malki MM, Asch AS, Wang ES, Jurcic JG, Bradley TJ, Flinn IW, Pollyea DA, Kambhampati S, Tanaka TN, Zeidner JF, Garcia-Manero G, Jeyakumar D, Komrokji R, Lancet J, Kantarjian HM, Gu L, Zhang Y, Tan A, Chao M, O'Hear C, Ramsingh G, Lal I, Vyas P, Daver NG. Magrolimab in combination with azacitidine in patients with higher-risk myelodysplastic syndromes: final results of a phase Ib study. J Clin Oncol. 2023;41(15):2815–2826. https://​doi.​org/​10.​1200/​JCO.​22.​01794.
98.
go back to reference Fischer T, Stone RM, Deangelo DJ, Galinsky I, Estey E, Lanza C, et al. Phase IIB trial of oral Midostaurin (PKC412), the FMS-like tyrosine kinase 3 receptor (FLT3) and multi-targeted kinase inhibitor, in patients with acute myeloid leukemia and high-risk myelodysplastic syndrome with either wild-type or mutated FLT3. J Clin Oncol. 2010;28(28):4339–45.PubMedPubMedCentralCrossRef Fischer T, Stone RM, Deangelo DJ, Galinsky I, Estey E, Lanza C, et al. Phase IIB trial of oral Midostaurin (PKC412), the FMS-like tyrosine kinase 3 receptor (FLT3) and multi-targeted kinase inhibitor, in patients with acute myeloid leukemia and high-risk myelodysplastic syndrome with either wild-type or mutated FLT3. J Clin Oncol. 2010;28(28):4339–45.PubMedPubMedCentralCrossRef
99.
go back to reference Strati P, Kantarjian H, Ravandi F, Nazha A, Borthakur G, Daver N, et al. Phase I/II trial of the combination of midostaurin (PKC412) and 5-azacytidine for patients with acute myeloid leukemia and myelodysplastic syndrome. Am J Hematol. 2015;90(4):276–81.PubMedPubMedCentralCrossRef Strati P, Kantarjian H, Ravandi F, Nazha A, Borthakur G, Daver N, et al. Phase I/II trial of the combination of midostaurin (PKC412) and 5-azacytidine for patients with acute myeloid leukemia and myelodysplastic syndrome. Am J Hematol. 2015;90(4):276–81.PubMedPubMedCentralCrossRef
100.
go back to reference Marie Sebert TC, Rauzy Odile Beyne, Bastard Aspasia Stamatoulas, Dimicoli-Salazar Sophie, Thepot Sylvain, Peterlin Pierre, Park Sophie, Gourin Marie-Pierre, Brehar Oana, Bally Cécile, Maury Sébastien, Fossard Gaelle, Selmi Lamya Ait Si, Chaffaut Cendrine, Clappier Emmanuelle, Itzykson Raphael, Chermat Fatiha, Chevret Sylvie, Fenaux Pierre, Ades Lionel. Ivosidenib monotherapy is effective in patients with IDH1 mutated myelodysplastic syndrome (MDS): the idiome phase 2 study by the GFM group. Blood. 2021;138:62.CrossRef Marie Sebert TC, Rauzy Odile Beyne, Bastard Aspasia Stamatoulas, Dimicoli-Salazar Sophie, Thepot Sylvain, Peterlin Pierre, Park Sophie, Gourin Marie-Pierre, Brehar Oana, Bally Cécile, Maury Sébastien, Fossard Gaelle, Selmi Lamya Ait Si, Chaffaut Cendrine, Clappier Emmanuelle, Itzykson Raphael, Chermat Fatiha, Chevret Sylvie, Fenaux Pierre, Ades Lionel. Ivosidenib monotherapy is effective in patients with IDH1 mutated myelodysplastic syndrome (MDS): the idiome phase 2 study by the GFM group. Blood. 2021;138:62.CrossRef
101.
go back to reference Stein EM, Fathi AT, DiNardo CD, Pollyea DA, Roboz GJ, Collins R, et al. Enasidenib in patients with mutant IDH2 myelodysplastic syndromes: a phase 1 subgroup analysis of the multicentre, AG221-C-001 trial. Lancet Haematol. 2020;7(4):e309–19.PubMedCrossRef Stein EM, Fathi AT, DiNardo CD, Pollyea DA, Roboz GJ, Collins R, et al. Enasidenib in patients with mutant IDH2 myelodysplastic syndromes: a phase 1 subgroup analysis of the multicentre, AG221-C-001 trial. Lancet Haematol. 2020;7(4):e309–19.PubMedCrossRef
Metadata
Title
Treatment of Myelodysplastic Syndromes for Older Patients: Current State of Science, Challenges, and Opportunities
Authors
Tariq Kewan
Maximillian Stahl
Jan Philipp Bewersdorf
Amer M. Zeidan
Publication date
18-04-2024
Publisher
Springer US
Published in
Current Hematologic Malignancy Reports
Print ISSN: 1558-8211
Electronic ISSN: 1558-822X
DOI
https://doi.org/10.1007/s11899-024-00733-y
Obesity Clinical Trial Summary

At a glance: The STEP trials

A round-up of the STEP phase 3 clinical trials evaluating semaglutide for weight loss in people with overweight or obesity.

Developed by: Springer Medicine

Highlights from the ACC 2024 Congress

Year in Review: Pediatric cardiology

Watch Dr. Anne Marie Valente present the last year's highlights in pediatric and congenital heart disease in the official ACC.24 Year in Review session.

Year in Review: Pulmonary vascular disease

The last year's highlights in pulmonary vascular disease are presented by Dr. Jane Leopold in this official video from ACC.24.

Year in Review: Valvular heart disease

Watch Prof. William Zoghbi present the last year's highlights in valvular heart disease from the official ACC.24 Year in Review session.

Year in Review: Heart failure and cardiomyopathies

Watch this official video from ACC.24. Dr. Biykem Bozkurt discuss last year's major advances in heart failure and cardiomyopathies.