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A. Wei, S. Strickland, G. Roboz, Jingzhou Hou, W. Fiedler, T. Lin, G. Martinelli, R. Walter, R. Walter, A. Enjeti, Kaffa Fakouhi, David Darden, M. Dunbar, Ming Zhu, S. Agarwal, A. Salem, M. Mabry, J. Hayslip (2016)
Safety and Efficacy of Venetoclax Plus Low-Dose Cytarabine in Treatment-Naive Patients Aged ≥65 Years with Acute Myeloid LeukemiaBlood, 128
S. Harel, Amina Cherait, C. Berthon, C. Willekens, Sophie Park, Marthe Rigal, S. Bréchignac, S. Thépot, B. Quesnel, C. Gardin, L. Adès, P. Fenaux, T. Braun (2015)
Outcome of patients with high risk Myelodysplastic Syndrome (MDS) and advanced Chronic Myelomonocytic Leukemia (CMML) treated with decitabine after azacitidine failure.Leukemia research, 39 5
D. Heudobler, S. Klobuch, Simone Thomas, J. Hahn, W. Herr, A. Reichle (2018)
Cutaneous Leukemic Infiltrates Successfully Treated With Biomodulatory Therapy in a Rare Case of Therapy-Related High Risk MDS/AMLFrontiers in Pharmacology, 9
P. Fenaux, G. Mufti, E. Hellstrom-Lindberg, V. Santini, C. Finelli, A. Giagounidis, R. Schoch, N. Gattermann, G. Sanz, A. List, S. Gore, J. Seymour, J. Bennett, J. Byrd, J. Backstrom, L. Zimmerman, D. McKenzie, C. Beach, L. Silverman (2009)
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.The Lancet. Oncology, 10 3
B. Chyla, R. Popovic, J. Potluri, J. Hayslip, Xin Huang, M. Zhu, M. Mabry, A. Bhathena (2016)
Correlative Biomarkers of Response to Venetoclax in Combination with Chemotherapy or Hypomethylating Agents in Elderly Untreated Patients with Acute Myeloid LeukemiaBlood, 128
This is the first phase III clinical trial of a new drug for patients with MDS after HMA failure
This study, although preclinical, provides the first in-vitro data suggesting modulation of the splicesosome machinery in leukemias harboring spliceosome mutations may be a new therapeutic approach
A. Ørskov, M. Treppendahl, Anni Skovbo, M. Holm, L. Friis, M. Hokland, K. Grønbæk (2015)
Hypomethylation and up-regulation of PD-1 in T cells by azacytidine in MDS/AML patients: A rationale for combined targeting of PD-1 and DNA methylationOncotarget, 6
This is the first report of the pharmacokinetic studies and clinical activity of an oral formulation of decitabine
M. Sébert, C. Bally, P. Peterlin, O. Beyne-Rauzy, L. Legros, M. Gourin, L. Sanhes, E. Wattel, E. Gyan, Sophie Park, A. Stamatoullas, A. Banos, K. Laribi, S. Jueliger, L. Bevan, C. Chaffaut, R. Sapena, Benedicte Samey, Fatiha Chermat, S. Chevret, L. Adès, P. Fenaux (2016)
Results of a Phase II Study of Guadecitabine (SGI-110) in Higher Risk MDS, CMML or Low Blast Count AML Patients Refractory to or Relapsing after Azacitidine (AZA) TreatmentBlood, 128
M. Festuccia, K. Baker, T. Gooley, B. Sandmaier, H. Deeg, B. Scott (2017)
Hematopoietic Cell Transplantation in Myelodysplastic Syndromes after Treatment with Hypomethylating Agents.Biology of blood and marrow transplantation : journal of the American Society for Blood and Marrow Transplantation, 23 9
E. Stein, A. Fathi, C. Dinardo, D. Pollyea, R. Swords, G. Roboz, R. Collins, M. Sekeres, R. Stone, E. Attar, A. Tosolini, Qiang Xu, M. Amatangelo, I. Gupta, R. Knight, S. Botton, M. Tallman, H. Kantarjian (2016)
Enasidenib (AG-221), a Potent Oral Inhibitor of Mutant Isocitrate Dehydrogenase 2 (IDH2) Enzyme, Induces Hematologic Responses in Patients with Myelodysplastic Syndromes (MDS)Blood, 128
E. Jabbour, G. Garcia-Manero, N. Batty, Jenny Shan, S. O'brien, J. Cortes, F. Ravandi, J. Issa, H. Kantarjian (2010)
Outcome of patients with myelodysplastic syndrome after failure of decitabine therapyCancer, 116
F. Ravandi, M. Alattar, M. Grunwald, M. Rudek, T. Rajkhowa, M. Richie, S. Pierce, N. Daver, G. Garcia-Manero, S. Faderl, A. Nazha, M. Konopleva, G. Borthakur, J. Burger, T. Kadia, S. Dellasala, M. Andreeff, J. Cortes, H. Kantarjian, M. Levis (2013)
Phase 2 study of azacytidine plus sorafenib in patients with acute myeloid leukemia and FLT-3 internal tandem duplication mutation.Blood, 121 23
Yue Wei, S. Dimicoli, C. Bueso-Ramos, Rui Chen, Hui Yang, D. Neuberg, S. Pierce, Yu Jia, Hong Zheng, Hui Wang, Xia Wang, M. Nguyen, Sa Wang, B. Ebert, R. Bejar, R. Levine, O. Abdel-Wahab, M. Kleppe, I. Ganan-Gomez, I. Ganan-Gomez, H. Kantarjian, G. Garcia-Manero (2013)
Toll-like receptor alterations in myelodysplastic syndromeLeukemia, 27
M. Daher, J. Lopez, J. Randhawa, K. Jabbar, Yue Wei, N. Pemmaraju, G. Borthakur, T. Kadia, M. Konopleva, H. Kantarjian, Katherine Hearn, Z. Estrov, Steven Reyes, C. Bueso-Ramos, G. Garcia-Manero (2017)
An exploratory clinical trial of bortezomib in patients with lower risk myelodysplastic syndromesAmerican Journal of Hematology, 92
Coleman Lindsley, W. Saber, B. Mar, R. Redd, Tao Wang, M. Haagenson, Peter Grauman, Zhen-Huan Hu, S. Spellman, Stephanie Lee, M. Verneris, K. Hsu, K. Fleischhauer, C. Cutler, J. Antin, D. Neuberg, B. Ebert (2017)
Prognostic Mutations in Myelodysplastic Syndrome after Stem‐Cell TransplantationThe New England Journal of Medicine, 376
(2016)
Modulation of splicing catalysis for therapeutic targeting of leukemia with mutations in genes encoding spliceosomal proteins, 22
This is the first report of a phase II study evaluating the activity of guadecitabine in patients with MDS with failure to prior therapy with HMAs
G. Garcia-Manero, O. Odenike, P. Amrein, D. Steensma, A. DeZern, L. Michaelis, S. Faderl, H. Kantarjian, J. Lowder, P. Taverna, A. Oganesian, Xiaoping Zhang, M. Azab, M. Savona (2016)
Successful Emulation of IV Decitabine Pharmacokinetics with an Oral Fixed-Dose Combination of the Oral Cytidine Deaminase Inhibitor (CDAi) E7727 with Oral Decitabine, in Subjects with Myelodysplastic Syndromes (MDS): Final Data of Phase 1 StudyBlood, 128
E. Jabbour, S. Faderl, K. Sasaki, T. Kadia, N. Daver, N. Pemmaraju, K. Patel, J. Khoury, C. Bueso-Ramos, Z. Bohannan, F. Ravandi, G. Borthakur, S. Verstovsek, Darla Miller, Rita Maduike, C. Hosing, H. Kantarjian, G. Garcia-Manero (2017)
Phase 2 study of low‐dose clofarabine plus cytarabine for patients with higher‐risk myelodysplastic syndrome who have relapsed or are refractory to hypomethylating agentsCancer, 123
G. Garcia-Manero, P. Fenaux, A. Al-Kali, M. Baer, M. Sekeres, G. Roboz, G. Gaidano, B. Scott, P. Greenberg, U. Platzbecker, D. Steensma, S. Kambhampati, K. Kreuzer, L. Godley, E. Atallah, R. Collins, H. Kantarjian, E. Jabbour, F. Wilhelm, N. Azarnia, L. Silverman (2016)
Rigosertib versus best supportive care for patients with high-risk myelodysplastic syndromes after failure of hypomethylating drugs (ONTIME): a randomised, controlled, phase 3 trial.The Lancet. Oncology, 17 4
T. Prebet, S. Gore, S. Thépot, B. Esterni, B. Quesnel, O. Rauzy, F. Dreyfus, C. Gardin, P. Fenaux, N. Vey (2012)
Outcome of acute myeloid leukaemia following myelodysplastic syndrome after azacitidine treatment failureBritish Journal of Haematology, 157
K. Neugebauer (2018)
Faculty Opinions recommendation of Modulation of splicing catalysis for therapeutic targeting of leukemia with mutations in genes encoding spliceosomal proteins.Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature
H. Kantarjian, J. Issa, C. Rosenfeld, J. Bennett, M. Albitar, J. Dipersio, V. Klimek, J. Slack, Carlos Castro, F. Ravandi, Richard Helmer, Lanlan Shen, S. Nimer, R. Leavitt, A. Raza, H. Saba (2006)
Decitabine improves patient outcomes in myelodysplastic syndromesCancer, 106
This is the first multicohort study evaluating single agent and combination immune checkpoint inhibitors for all MDS patients including frontline and after failure to HMAs
R. Stone, S. Mandrekar, B. Sanford, K. Laumann, S. Geyer, C. Bloomfield, C. Thiede, T. Prior, K. Döhner, G. Marcucci, F. Lo‐Coco, R. Klisovic, A. Wei, J. Sierra, M. Sanz, J. Brandwein, T. Witte, D. Niederwieser, F. Appelbaum, B. Medeiros, M. Tallman, J. Krauter, R. Schlenk, A. Ganser, H. Serve, G. Ehninger, S. Amadori, R. Larson, H. Döhner (2017)
Midostaurin plus Chemotherapy for Acute Myeloid Leukemia with a FLT3 MutationThe New England Journal of Medicine, 377
E. Jabbour, G. Garcia-Manero, P. Strati, A. Mishra, Najla Ali, E. Padron, J. Lancet, T. Kadia, N. Daver, S. O'brien, D. Steensma, M. Sekeres, S. Gore, A. DeZern, G. Roboz, A. List, H. Kantarjian, R. Komrokji (2015)
Outcome of patients with low‐risk and intermediate‐1‐risk myelodysplastic syndrome after hypomethylating agent failure: A report on behalf of the MDS Clinical Research ConsortiumCancer, 121
As with the previous study, this was one of the first studies to provide solid data on the impact of mutations in the outcomes of alloSCT in MDS
R. Bejar, K. Stevenson, B. Caughey, R. Lindsley, B. Mar, P. Stojanov, G. Getz, D. Steensma, J. Ritz, R. Soiffer, J. Antin, E. Alyea, P. Armand, V. Ho, J. Koreth, D. Neuberg, C. Cutler, B. Ebert (2014)
Somatic mutations predict poor outcome in patients with myelodysplastic syndrome after hematopoietic stem-cell transplantation.Journal of clinical oncology : official journal of the American Society of Clinical Oncology, 32 25
M. Konopleva, D. Pollyea, J. Potluri, B. Chyla, L. Hogdal, T. Busman, E. Mckeegan, A. Salem, Ming Zhu, J. Ricker, W. Blum, C. Dinardo, T. Kadia, M. Dunbar, R. Kirby, N. Falotico, J. Leverson, R. Humerickhouse, M. Mabry, R. Stone, H. Kantarjian, A. Letai (2016)
Efficacy and Biological Correlates of Response in a Phase II Study of Venetoclax Monotherapy in Patients with Acute Myelogenous Leukemia.Cancer discovery, 6 10
(2015)
Phase I/II trial of the combination of midostaurin (PKC412) and 5-azacytidine for patients with acute myeloid leukemia and myelodysplastic syndrome, 90
E. Stein, C. Dinardo, D. Pollyea, A. Fathi, G. Roboz, J. Altman, R. Stone, D. DeAngelo, R. Levine, I. Flinn, H. Kantarjian, R. Collins, M. Patel, A. Frankel, A. Stein, M. Sekeres, R. Swords, B. Medeiros, C. Willekens, P. Vyas, A. Tosolini, Qiang Xu, R. Knight, K. Yen, S. Agresta, S. Botton, M. Tallman (2017)
Enasidenib in mutant IDH 2 relapsed or refractory acute myeloid leukemia
Talha Badar, K. Patel, P. Thompson, C. Dinardo, Koichi Takahashi, M. Cabrero, G. Borthakur, J. Cortes, M. Konopleva, T. Kadia, Z. Bohannan, S. Pierce, E. Jabbour, F. Ravandi, N. Daver, R. Luthra, H. Kantarjian, G. Garcia-Manero (2015)
Detectable FLT3-ITD or RAS mutation at the time of transformation from MDS to AML predicts for very poor outcomes.Leukemia research, 39 12
G. Garcia-Manero, N. Daver, G. Montalban-Bravo, E. Jabbour, C. Dinardo, S. Kornblau, P. Bose, Y. Alvarado, M. Ohanian, G. Borthakur, J. Cortes, K. Naqvi, N. Pemmaraju, Xuelin Huang, G. Nogueras-Gonzalez, C. Bueso-Ramos, Yvonne Gasior, V. Bayer, S. Pierce, Hui Yang, S. Colla, H. Kantarjian (2016)
A Phase II Study Evaluating the Combination of Nivolumab (Nivo) or Ipilimumab (Ipi) with Azacitidine in Pts with Previously Treated or Untreated Myelodysplastic Syndromes (MDS)Blood, 128
J. Lancet, J. Cortes, D. Hogge, M. Tallman, T. Kovacsovics, L. Damon, R. Komrokji, S. Solomon, J. Kolitz, M. Cooper, A. Yeager, A. Louie, E. Feldman (2014)
Phase 2 trial of CPX-351, a fixed 5:1 molar ratio of cytarabine/daunorubicin, vs cytarabine/daunorubicin in older adults with untreated AML.Blood, 123 21
Hui Yang, C. Bueso-Ramos, C. Dinardo, M. Estecio, M. Davanlou, Qi-rong Geng, Z. Fang, M. Nguyen, S. Pierce, Yue Wei, S. Parmar, J. Cortes, H. Kantarjian, G. Garcia-Manero (2013)
Expression of PD-L1, PD-L2, PD-1 and CTLA4 in myelodysplastic syndromes is enhanced by treatment with hypomethylating agentsLeukemia, 28
T. Kadia, P. Jain, F. Ravandi, G. Garcia-Manero, M. Andreef, Koichi Takahashi, G. Borthakur, E. Jabbour, M. Konopleva, N. Daver, C. Dinardo, S. Pierce, R. Kanagal-Shamanna, K. Patel, Z. Estrov, J. Cortes, H. Kantarjian (2016)
TP53 mutations in newly diagnosed acute myeloid leukemia: Clinicomolecular characteristics, response to therapy, and outcomesCancer, 122
(2006)
Decitabine improves patient outcomes in myelodysplastic syndromes: results of a phase III randomized study, 106
This is one of the first multicenter and collaborative effort to determine the impact of mutations in outcomes of alloSCT for patients with MDS
M. Porta, A. Gallì, A. Bacigalupo, S. Zibellini, M. Bernardi, E. Rizzo, B. Allione, M. Lint, P. Pioltelli, P. Marenco, A. Bosi, M. Voso, S. Sica, Mariella Cuzzola, E. Angelucci, M. Rossi, M. Ubezio, A. Malovini, I. Limongelli, V. Ferretti, O. Spinelli, C. Tresoldi, S. Pozzi, S. Luchetti, L. Pezzetti, S. Catricalà, C. Milanesi, A. Riva, B. Bruno, F. Ciceri, F. Bonifazi, R. Bellazzi, E. Papaemmanuil, A. Santoro, E. Alessandrino, A. Rambaldi, M. Cazzola (2016)
Clinical Effects of Driver Somatic Mutations on the Outcomes of Patients With Myelodysplastic Syndromes Treated With Allogeneic Hematopoietic Stem-Cell Transplantation.Journal of clinical oncology : official journal of the American Society of Clinical Oncology, 34 30
G. Garcia-Manero, M. Tallman, G. Martinelli, V. Ribrag, Hui Yang, A. Balakumaran, S. Chlosta, Yayan Zhang, B. Smith (2016)
Pembrolizumab, a PD-1 Inhibitor, in Patients with Myelodysplastic Syndrome (MDS) after Failure of Hypomethylating Agent TreatmentBlood, 128
This study led to the approval of the first FLT3 inhibitor approved by the FDA
Purpose of reviewHypomethylating agents (HMAs) are the standard of care for patients with myelodysplastic syndromes (MDS). Although these agents induce responses in up to 40% of patients, most patients ultimately experience loss of response. The purpose of this review is to provide an overview of the different therapies under development for MDS after HMA therapy.Recent findingsRecent advances in the understanding of MDS pathogenesis have led to the development of new potential therapies after HMA failure. Newer HMAs, less susceptible to in-vivo deamination, such as guadecitabine or ASTX727 have shown activity. Alterations of immune checkpoints in MDS have led to multiple clinical trials evaluating the activity of monoclonal antibodies targeting these proteins (pembrolizumab, nivolumab, ipilimumab). Different combinations and new formulations of cytotoxic agents, such as clofarabine or CPX-351, are newer options for specific subsets of patients. Finally, targeted agents inhibiting multiple kinases (rigosertib), BCL2 (venetoclax) or mutant IDH1 (ivosidenib), IDH2 (enasidenib), FLT3 (sorafenib, midostaurin) or spliceosome components (H3B-8800) are other novel options.SummaryDespite the poor prognosis associated with HMA failure, clinical trials, new cytotoxic agents and allogeneic stem-cell transplantation, can offer therapeutic opportunities for these patients for whom there is no standard of care.
Current Opinion in Hematology – Wolters Kluwer Health
Published: Mar 1, 2018
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