A phase II study of decitabine and gemtuzumab ozogamicin in newly diagnosed and relapsed acute myeloid leukemia and high-risk myelodysplastic syndrome

Daver, Naval; Kantarjian, Hagop M.; Ravandi, Farhad; Estey, Elihu H.; Wang, Xuemei; Garcia‐Manero, Guillermo; Konopleva, Marina; O’Brien, Susan; Verstovšek, Srđan; Kadia, Tapan M.; DiNardo, Courtney D.; Pierce, Sherry; Huang, Xuelin; Pemmaraju, Naveen; Diaz-Pines-Mateo, Maria; Cortes, Jorge; Borthakur, Gautam

doi:10.1038/leu.2015.244

Cited by 66 publications

(48 citation statements)

References 43 publications

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“…Other agents that DNMT inhibitors have been combined with in clinical trials include lenalidomide, carboplatin, cisplatin, gemtuzumab ozogamicin, erythropoietin, filgrastim, romiplostim, bortezomib, arsenic trioxide, and sorafinib (Blum et al 2012;Sekeres et al 2012;Greenberg et al 2013;Ravandi et al 2013;Glasspool et al 2014;Navada et al 2014;Daver et al 2015). These trials have produced mixed results about whether the combinations are beneficial and require further investigation, although the trials investigating the sensitization of cancers to platinum compounds by pretreatment with hypomethylating drugs have been particularly promising (Matei et al 2012).…”

Section: Combination Therapy With Dna Hypomethylating Drugsmentioning

confidence: 99%

DNA Hypomethylating Drugs in Cancer Therapy

Sato

Issa

Kropf

2017

Cold Spring Harb Perspect Med

118

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Aberrant DNA methylation is a critically important modification in cancer cells, which, through promoter and enhancer DNA methylation changes, use this mechanism to activate oncogenes and silence of tumor-suppressor genes. Targeting DNA methylation in cancer using DNA hypomethylating drugs reprograms tumor cells to a more normal-like state by affecting multiple pathways, and also sensitizes these cells to chemotherapy and immunotherapy. The first generation hypomethylating drugs azacitidine and decitabine are routinely used for the treatment of myeloid leukemias and a next-generation drug (guadecitabine) is currently in clinical trials. This review will summarize preclinical and clinical data on DNA hypomethylating drugs as a cancer therapy.

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Section: Combination Therapy With Dna Hypomethylating Drugsmentioning

confidence: 99%

DNA Hypomethylating Drugs in Cancer Therapy

Sato

Issa

Kropf

2017

Cold Spring Harb Perspect Med

118

View full text Add to dashboard Cite

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“…These results suggest that an anti-CD33 antibody and 5-azacytidine may act in concert to promote tumor cell killing. Daver et al demonstrated that decitabine and gemtuzumab ozogamicin improved the response rate but not overall survival compared with historical outcomes in untreated AML 60 years (45). To further explore the hypothesis of combining a DNA-methyltransferase inhibitor with an anti-CD33 antibody the ongoing study includes a cohort combining SGN-CD33A with a DNA-methyltransferase inhibitor (azacytidine or decitabine) for elderly treatment naïve patients with AML.…”

Section: Strategies To Improve Frontline Therapy In Elderly Amlmentioning

confidence: 99%

Acute myeloid leukemia: advancing clinical trials and promising therapeutics

Daver

Cortés

Kantarjian

et al. 2016

Expert Review of Hematology

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Recent progress in understanding the biology of acute myeloid leukemia (AML) and the identification of targetable driver mutations, leukemia specific antigens and signal transduction pathways has ushered in a new era of therapy. In many circumstances the response rates with such targeted or antibody-based therapies are superior to those achieved with standard therapy and with decreased toxicity. In this review we discuss novel therapies in AML with a focus on two major areas of unmet need: (1) single agent and combination strategies to improve frontline therapy in elderly patients with AML and (2) molecularly targeted therapies in the frontline and salvage setting in all patients with AML.

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“…In patients receiving decitabine monotherapy, the rate of CR and overall response (OR) has been reported to be 13–39 and 32–70%, respectively (Iastrebner et al 2010; Kantarjian et al 2007a, c; Lee et al 2011; Oki et al 2012; Steensma et al 2009). Decitabine in combination with a variety of agents, including histone deacetylase inhibitors, thalidomide, and conventional chemotherapeutics, has been developed to treat intermediate- and high-risk MDS and AML (Blum et al 2007; Daver et al 2016; Gao et al 2015; Garcia-Manero et al 2006; Geng et al 2016; Jiang et al 2015; Kirschbaum et al 2014; Li et al 2015; Song et al 2012; Yang et al 2005; Zhao et al 2015). Several studies showed that decitabine in combination with chemotherapy improved the outcomes in patients with relapsed/refractory AML or AML transformed from MDS (MDS/AML) (Leonard et al 2014; Li et al 2015; Scandura et al 2011; Song et al 2012).…”

Section: Introductionmentioning

confidence: 99%

Decitabine priming prior to low-dose chemotherapy improves patient outcomes in myelodysplastic syndromes-RAEB: a retrospective analysis vs. chemotherapy alone

Ren

Zhou

et al. 2017

J Cancer Res Clin Oncol

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PurposeThe aim of this study was to examine whether decitabine priming prior to low-dose chemotherapeutic regimens could improve outcomes in patients with myelodysplastic syndromes—refractory anemia with excess of blasts (MDS-RAEB).MethodsThe current retrospective analysis included all MDS-RAEB patients receiving idarubicin/cytarabine (IA) or aclacinomycin/cytarabine (AA), with or without decitabine priming during a period from February 2010 to May 2015. Treatment response and toxicity were compared between patients receiving decitabine priming and those who did not. A panel of 6 MDS-related genes was examined using bone marrow specimens.ResultsA total of 81 patients were included in the analysis: 40 received decitabine priming prior to chemotherapy (decitabine priming group). The median follow-up was 10.9 months (IQR: 6.2–21.9). The rate of overall response (OR) and complete remission (CR) was significantly higher in the decitabine priming group than in the chemotherapy group (OR: 75.0 vs. 51.2%, p = 0.027; CR: 55.0 vs. 29.3%, p = 0.019). Overall survival (OS) did not differ significantly between the two groups (19.5 vs. 14.7 months, p = 0.082). In a subgroup analysis that included only patients at < 60 years of age, the CR rate in the decitabine priming group was significantly higher than in the chemotherapy group (65.5 vs. 31.0%, p = 0.009). Survival benefit of decitabine priming was apparent in patients at < 60 years of age (22.4 months with 95% CI of 6.7–38.1 vs. 14.7 months with 95% CI of 11.4–18.0 months in the chemotherapy group, p = 0.028), patients with intermediate and unfavorable karyotypes (22.4 months with 95% CI of 15.1–29.7 vs. 11.9 months with 95% CI of 4.0–19.8 months in the chemotherapy group, p = 0.042), and patients with mutated splicing factor genes (35.3 months with 95% CI of 21.4–49.2 vs. 17.8 months with 95% CI of 13.8–21.8 months in the chemotherapy group, p = 0.039). Grade 3–4 hematological and non-hematological toxicities were not significantly different between the two groups.ConclusionsDecitabine priming prior to low-dose chemotherapy could improve treatment responses in patients with MDS-RAEB.

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A phase II study of decitabine and gemtuzumab ozogamicin in newly diagnosed and relapsed acute myeloid leukemia and high-risk myelodysplastic syndrome

Cited by 66 publications

References 43 publications

DNA Hypomethylating Drugs in Cancer Therapy

DNA Hypomethylating Drugs in Cancer Therapy

Acute myeloid leukemia: advancing clinical trials and promising therapeutics

Decitabine priming prior to low-dose chemotherapy improves patient outcomes in myelodysplastic syndromes-RAEB: a retrospective analysis vs. chemotherapy alone

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