Sustained Leukemia-Free State and Molecular Response to Sorafenib in a Patient With Chronic Myelomonocytic Leukemia in Transformation Driven by Homozygous FLT3-ITD Malignant Hematopoiesis

Kosmider, Olivier; Chapuis, Nicolas; Kaltenbach, Sophie; Rouquette, P. Boudou; Willems, Lise; Chesnais, Virginie; Radford‐Weiss, Isabelle; Bardet, Valérie; Mayeux, Patrick; Tamburini, Jérôme; Fontenay, Michaëla; Bouscary, Didier

doi:10.1016/j.clml.2012.11.007

Cited by 3 publications

(2 citation statements)

References 14 publications

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“…However, rare tumors containing activating FLT3 variants have been treated with FLT3 inhibitors. 151,152 Other signaling pathway components, such as JAK2, KRAS/NRAS, mitogen-activated protein kinase (MAPK), and mitogenactivated protein/extracellular signal-regulated kinase (MEK), as well as methylation pathway components, such as IDH1/2, have been the focus of targeted therapy development. 153 Clonal architecture studies in CMML have shown similar findings to those identified in MDS, as discussed above: variants in genes involved in methylation or RNA splicing, in particular ASXL1, TET2, and SRSF2, are identified early; and variants in genes encoding transcription factors and signaling/other pathway components appear later in clonal progression.…”

Section: Chronic Myelomonocytic Leukemiamentioning

confidence: 99%

Clinical Significance of DNA Variants in Chronic Myeloid Neoplasms

McClure

Ewalt

Crow

et al. 2018

The Journal of Molecular Diagnostics

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To address the clinical relevance of small DNA variants in chronic myeloid neoplasms (CMNs), an Association for Molecular Pathology Working Group comprehensively reviewed published literature, summarized key findings that support clinical utility, and defined critical gene inclusions for high-throughput sequencing testing panels. This review highlights the biological complexity of CMNs [including myelodysplastic syndromes, myeloproliferative neoplasms, entities with overlapping features (myelodysplastic syndromes/myeloproliferative neoplasms), and systemic mastocytosis], the genetic heterogeneity within diagnostic categories, and similarities between apparently disparate diagnostic entities. The founding variant's hematopoietic differentiation compartment, specific genes and variants present, order of variant appearance, individual subclone dynamics, and therapeutic intervention all contribute to the clinicopathologic features of CMNs. Selection and efficacy of targeted therapies are increasingly based on DNA variant profiles present at various time points; therefore, high-throughput sequencing remains critical for patient management. The following genes are a minimum recommended list to provide relevant clinical information for the management of most CMNs: ASXL1, BCOR, BCORL1, CALR, CBL, CEBPA, CSF3R, DNMT3A, ETV6, EZH2, FLT3, IDH1, IDH2, JAK2, KIT, KRAS, MPL, NF1, NPM1, NRAS, PHF6, PPM1D, PTPN11, RAD21, RUNX1, SETBP1, SF3B1, SMC3, SRSF2, STAG2, TET2, TP53, U2AF1, and ZRSR2. This list is not comprehensive for all myeloid neoplasms and will evolve as insights into effects of combinations of relevant biomarkers on specific clinicopathologic characteristics of CMNs accumulate.

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Section: Chronic Myelomonocytic Leukemiamentioning

confidence: 99%

Clinical Significance of DNA Variants in Chronic Myeloid Neoplasms

McClure

Ewalt

Crow

et al. 2018

The Journal of Molecular Diagnostics

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“…The result showed sorafenib with synergy of cGvHD can achieve high rates of sustained remission in high-risk patients. 42 There were 2 case reports about successful treatment of CMML using sorafenib 43,44 Mutations of DNMT3A and FLT3 influenced the pathophysiology of leukemia at a different angle, the combination of FLT3 and DNA methyltransferase inhibition is synergistically cytotoxic to FLT3/ITD AML cells. 48 The case in our report received decitabine and sorafenib combined treatment and got approximately 10 months' remission.…”

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confidence: 99%

Chronic myelomonocytic leukemia with double-mutations in DNMT3A and FLT3-ITD treated with decitabine and sorafenib

Wang

Xiao

et al. 2017

Cancer Biology & Therapy

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Chronic myelomonocytic leukemia (CMML) is a heterogeneous neoplastic hematologic disorder with worse overall survival. Half of CMML have mutations, but case with concomitant mutations of DNA methyltransferase 3A (DNMT3A) and Internal tandem duplications of the juxtamembrane domain of FLT3 (FLT3-ITD) in CMML was not reported before. We reported a 51-year-old man who had CMML with concomitant mutations in DNMT3A and FLT3-ITD.The patient received decitabine and sorafenib combined treatment. In this report, we reviewed DNMT3A mutation and FLT3 mutation, and we reviewed treatment of decitabine and sorafenib. This report is significant. First: This is the first report on CMML with doublemutations of DNMT3A and FLT3-ITD. Second: It shows the importance of targeted drug in combined treatment of CMML.

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Drug safety evaluation of sorafenib for treatment of solid tumors: consequences for the risk assessment and management of cancer patients

Huillard¹,

Boissier²,

Blanchet³

et al. 2014

Expert Opinion on Drug Safety

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The systematic multi-disciplinary risk assessment of cancer patients prior to TKI initiation reduces the risks of acute and late toxicity, especially drug-drug interactions and arterial risks. Sarcopenia is now identified as a major risk of severe toxicity. The very diverse clinical pictures of cumulative toxicity must be known. The monitoring of sorafenib systemic exposure is helpful especially in elderly patients. Moreover, at disease progression, it allows distinguishing between underexposure to sorafenib and truly acquired resistance to the drug. The optimal use of sorafenib should allow improving the reported results of flat-dose. Finally, most of this knowledge could be used for the development and optimal use of the other TKIs.

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Sustained Leukemia-Free State and Molecular Response to Sorafenib in a Patient With Chronic Myelomonocytic Leukemia in Transformation Driven by Homozygous FLT3-ITD Malignant Hematopoiesis

Cited by 3 publications

References 14 publications

Clinical Significance of DNA Variants in Chronic Myeloid Neoplasms

Clinical Significance of DNA Variants in Chronic Myeloid Neoplasms

Chronic myelomonocytic leukemia with double-mutations in DNMT3A and FLT3-ITD treated with decitabine and sorafenib

Drug safety evaluation of sorafenib for treatment of solid tumors: consequences for the risk assessment and management of cancer patients

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