Publications by authors named "Laetitia Largeaud"

24 Publications

  • Page 1 of 1

GATA2 deficiency phenotype associated with tandem duplication GATA2 and over-expression of GATA2-AS1.

Blood Adv 2021 Oct 12. Epub 2021 Oct 12.

NIHR Newcastle Biomedical Research Centre, United Kingdom.

A 3-year old girl of non-consanguineous healthy parents presented with cervical and mediastinal lymphadenopathy due to Mycobacterium fortuitum infection. Routine blood analysis showed normal hemoglobin, neutrophils and platelets but profound mononuclear cell deficiency (monocytes <0.1x109/L; B cells 78/µL; NK cells 48/µL). A 548,902bp region containing GATA2 was sequenced by targeted capture and deep sequencing. This revealed a de novo 187Kb duplication of the entire GATA2 locus, containing a maternally inherited copy number variation deletion of 25Kb (GRCh37: esv2725896 and nsv513733). Many GATA2-associated phenotypes have been attributed to amino acid substitution, frameshift/deletion, loss of intronic enhancer function or aberrant splicing. Gene deletion has been described but other structural variation has not been reported in the germline configuration. In this case, duplication of the GATA2 locus was paradoxically associated with skewed, diminished expression of GATA2 mRNA and loss of GATA2 protein. Chimeric RNA fusion transcripts were not detected. A possible mechanism involves increased transcription of the anti-sense long-non-coding (lnc)RNA GATA2-AS1 (RP11-472.220) which was increased several-fold. This case further highlights that evaluation of the allele count is essential in any case of suspected GATA2-related syndrome.
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http://dx.doi.org/10.1182/bloodadvances.2021005217DOI Listing
October 2021

The CADM1 tumor suppressor gene is a major candidate gene in MDS with deletion of the long arm of chromosome 11.

Blood Adv 2021 Oct 12. Epub 2021 Oct 12.

Belgian Cancer Registry, Brussels, Belgium.

Myelodysplastic syndromes (MDS) represent a heterogeneous group of clonal hematopoietic stem-cell disorders characterized by ineffective hematopoiesis leading to peripheral cytopenias and in a substantial proportion of cases to acute myeloid leukemia. The deletion of the long arm of chromosome 11, del(11q), is a rare but recurrent clonal event in MDS. Here, we detail the largest series of 113 cases of MDS and myelodysplastic syndromes/myeloproliferative neoplasms (MDS/MPN) harboring a del(11q) analyzed at clinical, cytological, cytogenetic and molecular levels. Female predominance, a survival prognosis similar to other MDS, a low monocyte count and dysmegakaryopoiesis were the specific clinical and cytological features of del(11q) MDS. In most cases, del(11q) was isolated, primary and interstitial encompassing the 11q22-23 region containing ATM, KMT2A and CBL genes. The common deleted region at 11q23.2 is centered on an intergenic region between CADM1 (also known as TSLC1, Tumour Suppressor in Lung Cancer 1) and NXPE2. CADM1 was expressed in all myeloid cells analyzed in contrast to NXPE2. At the functional level, the deletion of Cadm1 in murine Lineage-Sca1+Kit+ cells modifies the lymphoid to myeloid ratio in bone marrow although not altering their multi-lineage hematopoietic reconstitution potential after syngenic transplantation. Together with the frequent simultaneous deletions of KMT2A, ATM and CBL and mutations of ASXL1, SF3B1 and CBL, we show that CADM1 may be important in the physiopathology of the del(11q) MDS, extending its role as tumor-suppressor gene from solid tumors to hematopoietic malignancies.
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http://dx.doi.org/10.1182/bloodadvances.2021005311DOI Listing
October 2021

Diet of neutrophils by bone marrow macrophages in autoimmune neutropenia.

Blood 2021 Aug;138(7):584

Institut Universitaire du Cancer de Toulouse-Oncopole.

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http://dx.doi.org/10.1182/blood.2021011947DOI Listing
August 2021

Characteristic vacuolization of myeloid precursors and UBA1 mutation in a woman with monosomy X.

Int J Lab Hematol 2021 Jun 10. Epub 2021 Jun 10.

Laboratoire d'Hématologie, Centre Hospitalo-universitaire (CHU) de Toulouse, Institut Universitaire du Cancer de Toulouse-Oncopole (IUCT-O), Toulouse, France.

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http://dx.doi.org/10.1111/ijlh.13617DOI Listing
June 2021

Characteristic vacuolisation of granulocytic and erythroid precursors associated with VEXAS syndrome.

Br J Haematol 2021 Jul 2;194(1). Epub 2021 Mar 2.

Haematology Laboratory Medicine, Cancer University Institute of Toulouse - Oncopole, Toulouse, France.

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http://dx.doi.org/10.1111/bjh.17381DOI Listing
July 2021

Longitudinal CITE-Seq profiling of chronic lymphocytic leukemia during ibrutinib treatment: evolution of leukemic and immune cells at relapse.

Biomark Res 2020 Dec 9;8(1):72. Epub 2020 Dec 9.

Centre de Recherches en Cancérologie de Toulouse, INSERM UMR1037, Toulouse, France.

Background: Ibrutinib, an irreversible Bruton Tyrosine Kinase (BTK) inhibitor, has revolutionized Chronic Lymphocytic Leukemia (CLL) treatment, but resistances to ibrutinib have emerged, whether related or not to BTK mutations. Patterns of CLL evolution under ibrutinib therapy are well characterized for the leukemic cells but not for their microenvironment.

Methods: Here, we addressed this question at the single cell level of both transcriptome and immune-phenotype. The PBMCs from a CLL patient were monitored during ibrutinib treatment using Cellular Indexing of Transcriptomes and Epitopes by sequencing (CITE-Seq) technology.

Results: This unveiled that the short clinical relapse of this patient driven by BTK mutation is associated with intraclonal heterogeneity in B leukemic cells and up-regulation of common signaling pathways induced by ibrutinib in both B leukemic cells and immune cells. This approach also pinpointed a subset of leukemic cells present before treatment and highly enriched during progression under ibrutinib. These latter exhibit an original gene signature including up-regulated BCR, MYC-activated, and other targetable pathways. Meanwhile, although ibrutinib differentially affected the exhaustion of T lymphocytes, this treatment enhanced the T cell cytotoxicity even during disease progression.

Conclusions: These results could open new alternative of therapeutic strategies for ibrutinib-refractory CLL patients, based on immunotherapy or targeting B leukemic cells themselves.
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http://dx.doi.org/10.1186/s40364-020-00253-wDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7724843PMC
December 2020

CD5+CD200- B-cell neoplasms deserve an extra look.

Ann Biol Clin (Paris) 2021 Feb;79(1):90-91

Haematology Laboratory, Cancer University Institute of Toulouse, Oncopole, Toulouse, France.

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http://dx.doi.org/10.1684/abc.2020.1610DOI Listing
February 2021

Do not forget megakaryocytes morphology when you deal with chronic myeloid leukaemia.

Ann Biol Clin (Paris) 2020 Dec;78(6):691-692

Haematology laboratory, Cancer University Institute of Toulouse, Oncopole, France.

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http://dx.doi.org/10.1684/abc.2020.1595DOI Listing
December 2020

Impact of TP53 mutations in acute myeloid leukemia patients treated with azacitidine.

PLoS One 2020 1;15(10):e0238795. Epub 2020 Oct 1.

Laboratoire d'Hématologie, Centre Hospitalier Universitaire de Toulouse, Institut Universitaire du Cancer de Toulouse Oncopole, Toulouse, France.

Hypomethylating agents are a classical frontline low-intensity therapy for older patients with acute myeloid leukemia. Recently, TP53 gene mutations have been described as a potential predictive biomarker of better outcome in patients treated with a ten-day decitabine regimen., However, functional characteristics of TP53 mutant are heterogeneous, as reflected in multiple functional TP53 classifications and their impact in patients treated with azacitidine is less clear. We analyzed the therapeutic course and outcome of 279 patients treated with azacitidine between 2007 and 2016, prospectively enrolled in our regional healthcare network. By screening 224 of them, we detected TP53 mutations in 55 patients (24.6%), including 53 patients (96.4%) harboring high-risk cytogenetics. The identification of any TP53 mutation was associated with worse overall survival but not with response to azacitidine in the whole cohort and in the subgroup of patients with adverse karyotype. Stratification of patients according to three recent validated functional classifications did not allow the identification of TP53 mutated patients who could benefit from azacitidine. Systematic TP53 mutant classification will deserve further exploration in the setting of patients treated with conventional therapy and in the emerging field of therapies targeting TP53 pathway.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0238795PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7529302PMC
November 2020

Lomustine is beneficial to older AML with ELN2017 adverse risk profile and intermediate karyotype: a FILO study.

Leukemia 2021 05 18;35(5):1291-1300. Epub 2020 Sep 18.

Clinical Hematology, Bordeaux University Hospital, Bordeaux University, Inserm 1035, Bordeaux, France.

We previously reported the benefit of lomustine addition to conventional chemotherapy in older acute myeloid leukemias with nonadverse chromosomal aberrations in the LAM-SA 2007 randomized clinical trial (NCT00590837). A molecular analysis of 52 genes performed in 330 patients included in this trial, 163 patients being treated with lomustine in combination with idarubicin and cytarabine and 167 without lomustine, identified 1088 mutations with an average of 3.3 mutations per patient. NPM1, FLT3, and DNMT3A were the most frequently mutated genes. A putative therapeutic target was identified in 178 patients (54%). Among five molecular classifications analyzed, the ELN2017 risk classification has the stronger association with the clinical evolution. Patients not treated with lomustine have an expected survival prognosis in agreement with this classification regarding the overall and event-free survivals. In strong contrast, lomustine erased the ELN2017 classification prognosis. The benefit of lomustine in nonadverse chromosomal aberrations was restricted to patients with RUNX1, ASXL1, TP53, and FLT3-ITD/NPM1 mutations in contrast to the intermediate and favorable ELN2017 patients. This post-hoc analysis identified a subgroup of fit elderly AML patients with intermediate cytogenetics and molecular markers who may benefit from lomustine addition to intensive chemotherapy.
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http://dx.doi.org/10.1038/s41375-020-01031-1DOI Listing
May 2021

Acute myeloid leukemia with myelodysplasia-related changes and basophilic differentiation.

Blood Res 2020 Sep;55(3):130

Clinical Pathology Laboratory, Cancer University Institute of Toulouse, Oncopole, France.

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http://dx.doi.org/10.5045/br.2020.2020095DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7536570PMC
September 2020

Clonal haematopoiesis is increased in early onset in systemic sclerosis.

Rheumatology (Oxford) 2020 11;59(11):3499-3504

Sorbonne Université, INSERM U938, Centre de Recherche Saint-Antoine (CRSA).

Objectives: SSc is an autoimmune disease characterized by fibrosis, microangiopathy and immune dysfunctions including dysregulation of proinflammatory cytokines. Clonal haematopoiesis of indeterminate potential (CHIP) is defined by the acquisition of somatic mutations in haematopoietic stem cells leading to detectable clones in the blood. Recent data have shown a higher risk of cardiovascular disease in patients with CHIP resulting from increased production of proinflammatory cytokines and accelerated atherosclerosis. Eventual links between CHIP and autoimmune diseases are undetermined. The aim of our study was to evaluate the prevalence of CHIP in SSc patients and its association with clinical phenotype.

Methods: Forty-one genes frequently mutated in myeloid malignancies were sequenced in peripheral blood mononuclear cells from 90 SSc patients and 44 healthy donors.

Results: A total of 15 somatic variants were detected in 13/90 SSc patients (14%) and four somatic variants in 4/44 (9%) healthy donors (HD) (P = 0.58). The prevalence of CHIP was significantly higher in younger SSc patients than in HD: 25% (6/24) vs 4% (1/26) (P = 0.045) under 50 years and 17% (7/42) vs 3% (1/38) (P = 0.065) under 60 years. The prevalence of CHIP in patients over 70 years was similar in SSc patients and healthy donors. The most common mutations occurred in DNMT3A (seven variants). No major clinical differences were observed between SSc patients with or without CHIP.

Conclusion: Whether CHIP increases the risk to develop SSc or is a consequence of a SSc-derived modified bone marrow micro-environment remains to be explored.
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http://dx.doi.org/10.1093/rheumatology/keaa282DOI Listing
November 2020

Real-World Outcomes of Patients with Refractory or Relapsed -ITD Acute Myeloid Leukemia: A Toulouse-Bordeaux DATAML Registry Study.

Cancers (Basel) 2020 Jul 24;12(8). Epub 2020 Jul 24.

Service d'Hématologie, Institut Universitaire du Cancer de Toulouse Oncopole, Centre Hospitalier Universitaire de Toulouse, 31000 Toulouse, France.

Two recent phase 3 trials showed that outcomes for relapsed/refractory (R/R) -mutated acute myeloid leukemia (AML) patients may be improved by a single-agent tyrosine kinase inhibitor (TKI) (i.e., quizartinib or gilteritinib). In the current study, we retrospectively investigated the characteristics and real-world outcomes of R/R -internal tandem duplication (ITD) acute myeloid leukemia (AML) patients in the Toulouse-Bordeaux DATAML registry. In the study, we included 316 patients with -ITD AML that received intensive chemotherapy as a first-line treatment. The rate of complete remission (CR) or CR without hematological recovery (CRi) was 75.2%, and 160 patients were R/R after a first-line TKI-free treatment ( = 294). Within the subgroup of R/R patients that fulfilled the main criteria of the QUANTUM-R study, 48.9% received an intensive salvage regimen; none received hypomethylating agents or low-dose cytarabine. Among the R/R -ITD AML patients with CR1 durations < 6 months who received intensive TKI-free treatment, the rate of CR or CRi after salvage chemotherapy was 52.8%, and these results allowed a bridge to be transplanted in 39.6% of cases. Finally, in this QUANTUM-R standard arm-matched cohort, the median overall survival (OS) was 7.0 months and 1-, 3- and 5-year OS were 30.2%, 23.7% and 21.4%, respectively. To conclude, these real-world data show that the intensity of the second-line treatment likely affects response and transplantation rates. Furthermore, the results indicate that including patients with low-intensity regimens, such as low-dose cytarabine or hypomethylating agents, in the control arm of a phase 3 trial may be counterproductive and could compromise the results of the study.
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http://dx.doi.org/10.3390/cancers12082044DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7465142PMC
July 2020

Dendrogenin A synergizes with Cytarabine to Kill Acute Myeloid Leukemia Cells In Vitro and In Vivo.

Cancers (Basel) 2020 Jun 29;12(7). Epub 2020 Jun 29.

Unité Mixte de Recherche (UMR)1037, Cancer Research Center of Toulouse (CRCT), Institut National de la Santé et de la Recherche Médicale (INSERM) Université de Toulouse, Team Cholesterol Metabolism and Therapeutic Innovations, Equipe labellisée par la Ligue Contre le Cancer, 31037 Toulouse, France.

Dendrogenin A (DDA) is a mammalian cholesterol metabolite that displays potent antitumor properties on acute myeloid leukemia (AML). DDA triggers lethal autophagy in cancer cells through a biased activation of the oxysterol receptor LXRβ, and the inhibition of a sterol isomerase. We hypothesize that DDA could potentiate the activity of an anticancer drug acting through a different molecular mechanism, and conducted in vitro and in vivo combination tests on AML cell lines and patient primary tumors. We report here results from tests combining DDA with antimetabolite cytarabine (Ara-C), one of the main drugs used for AML treatment worldwide. We demonstrated that DDA potentiated and sensitized AML cells, including primary patient samples, to Ara-C in vitro and in vivo. Mechanistic studies revealed that this sensitization was LXRβ-dependent and was due to the activation of lethal autophagy. This study demonstrates a positive in vitro and in vivo interaction between DDA and Ara-C, and supports the clinical evaluation of DDA in combination with Ara-C for the treatment of AML.
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http://dx.doi.org/10.3390/cancers12071725DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7407291PMC
June 2020

Dactinomycin in acute myeloid leukemia with NPM1 mutations.

Eur J Haematol 2020 Sep 25;105(3):302-307. Epub 2020 May 25.

Service d'Hématologie, Institut Universitaire du Cancer de Toulouse Oncopole, Centre Hospitalier Universitaire de Toulouse, Toulouse, France.

Objectives: Complete responses have been observed in NPM1-mutated AML patients with dactinomycin, a nucleolar stress-inducing drug. Here, we report a single-center experience of compassionate use of dactinomycin in untreated or relapsed/ refractory NPM1-mutated AML.

Methods: From September 2015 to February 2019, 26 adult patients with NPM1-mutated AML received dactinomycin in different situations: front-line treatment in 4 unfit patients (16%); morphologic (n = 16, 62%), molecular relapses (n = 4, 16%), refractory disease (n = 1, 13%), or postremission therapy in second complete response (n = 1, 13%).

Results: Median age was 62.5 years. Median number of dactinomycin cycle was 1 (1-8), and 7 patients (27%) received more than 3 cycles. Three out of 17 patients (18%) in morphologic relapse or refractory to chemotherapy achieved complete remission after the first cycle of dactinomycin. None of the 4 patients unfit for intensive chemotherapy responded to dactinomycin as front-line therapy. Grade 3-4 adverse events were thrombocytopenia (n = 11, 42%), neutropenia (n = 11, 42%), GI toxicity (n = 6, 23%), mucositis (n = 5, 19%), lung infection (n = 5, 19%), and skin rash (n = 2, 7.6%).

Conclusions: Dactinomycin is an inexpensive and easily available drug that may induce significant responses in few AML patients with NPM1 mutations with an acceptable safety profile.
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http://dx.doi.org/10.1111/ejh.13438DOI Listing
September 2020

CD34CD38CD123 Leukemic Stem Cell Frequency Predicts Outcome in Older Acute Myeloid Leukemia Patients Treated by Intensive Chemotherapy but Not Hypomethylating Agents.

Cancers (Basel) 2020 May 6;12(5). Epub 2020 May 6.

Université Toulouse III Paul Sabatier, 31330 Toulouse, France.

The prognostic impact of immunophenotypic CD34CD38CD123 leukemic stem cell (iLSC) frequency at diagnosis has been demonstrated in younger patients treated by intensive chemotherapy, however, this is less clear in older patients. Furthermore, the impact of iLSC in patients treated by hypomethylating agents is unknown. In this single-center study, we prospectively assessed the CD34CD38CD123 iLSC frequency at diagnosis in acute myeloid leukemia (AML) patients aged 60 years or older. In a cohort of 444 patients, the median percentage of iLSC at diagnosis was 4.3%. Significant differences were found between treatment groups with a lower median in the intensive chemotherapy group (0.6%) compared to hypomethylating agents (8.0%) or supportive care (11.1%) ( <0.0001). In the intensive chemotherapy group, the median overall survival was 34.5 months in patients with iLSC ≤0.10% and 14.6 months in patients with >0.10% ( = 0.031). In the multivariate analyses of this group, iLSC frequency was significantly and independently associated with the incidence of relapse, event-free, relapse-free, and overall survival. However, iLSC frequency had no prognostic impact on patients treated by hypomethylating agents. Thus, the iLSC frequency at diagnosis is an independent prognostic factor in older acute myeloid patients treated by intensive chemotherapy but not hypomethylating agents.
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http://dx.doi.org/10.3390/cancers12051174DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7281486PMC
May 2020

Outcome of Relapsed or Refractory -Mutated Acute Myeloid Leukemia Before Second-Generation FLT3 Tyrosine Kinase Inhibitors: A Toulouse-Bordeaux DATAML Registry Study.

Cancers (Basel) 2020 Mar 25;12(4). Epub 2020 Mar 25.

CHU Bordeaux, Service d'Hématologie Clinique et de Thérapie Cellulaire, F-33000, Bordeaux, France.

A recent phase 3 trial showed that the outcome of patients with relapsed/refractory (R/R) -mutated acute myeloid leukemia (AML) improved with gilteritinib, a single-agent second-generation FLT3 tyrosine kinase inhibitor (TKI), compared with standard of care. In this trial, the response rate with standard therapy was particularly low. We retrospectively assessed the characteristics and outcome of patients with R/R -mutated AML included in the Toulouse-Bordeaux DATAML registry. Among 347 patients who received FLT3 TKI-free intensive chemotherapy as first-line treatment, 174 patients were refractory ( = 48, 27.6%) or relapsed ( = 126, 72.4%). Salvage treatments consisted of intensive chemotherapy ( = 99, 56.9%), azacitidine or low-dose cytarabine ( = 9, 5.1%), other low-intensity treatments ( = 17, 9.8%), immediate allogeneic stem cell transplantation ( = 4, 2.3%) or best supportive care only ( = 45, 25.9%). Among the 114 patients who previously received FLT3 TKI-free intensive chemotherapy as first-line treatment (refractory, = 32, 28.1%; relapsed, = 82, 71.9%), the rate of CR (complete remission) or CRi (complete remission with incomplete hematologic recovery) after high- or low-intensity salvage treatment was 50.0%, with a bridge to transplant in 34.2% ( = 39) of cases. The median overall survival (OS) was 8.2 months (interquartile range, 3.0-32); 1-, 3- and 5-year OS rates were 36.0% (95%CI: 27-45), 24.7% (95%CI: 1-33) and 19.7% (95%CI: 1-28), respectively. In this real-word study, although response rate appeared higher than the controlled arm of the ADMIRAL trial, the outcome of patients with R/R -mutated AML remains very poor with standard salvage therapy.
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http://dx.doi.org/10.3390/cancers12040773DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7226007PMC
March 2020

More than ten percent of relapses occur after five years in AML patients with mutation.

Leuk Lymphoma 2020 05 5;61(5):1226-1229. Epub 2020 Feb 5.

Service d'Hématologie, Institut Universitaire du Cancer de Toulouse-Oncopole, Centre Hospitalier Universitaire de Toulouse, Toulouse, France.

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http://dx.doi.org/10.1080/10428194.2019.1706733DOI Listing
May 2020

Do not jump to hasty conclusions: all gamma delta T-cells neoplasms are not aggressive!

Blood Res 2019 Dec 20;54(4):243. Epub 2019 Dec 20.

Laboratory of Haematology, University Cancer Institute of Toulouse, Toulouse, France.

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http://dx.doi.org/10.5045/br.2019.54.4.243DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6942139PMC
December 2019

Outcome of AML patients with IDH2 mutations in real world before the era of IDH2 inhibitors.

Leuk Res 2019 06 27;81:82-87. Epub 2019 Apr 27.

Université Toulouse III Paul Sabatier, Toulouse, France; Cancer Research Center of Toulouse, UMR1037-INSERM, ERL5294 CNRS, Toulouse, France; Service d'Hématologie, Centre Hospitalier Universitaire de Toulouse, Institut Universitaire du Cancer de Toulouse Oncopole, Toulouse, France. Electronic address:

Describing the prognosis of sub-groups of acute myeloid leukemia (AML) patients treated in real world with current therapies is becoming increasingly relevant to estimate the benefit that new targeted drugs will bring in the field. This is particularly the case when novel drugs are registered on the basis of non-randomized studies. IDH2 inhibitors have recently emerged as promising drugs in patients with IDH2 or IDH2 mutations. Enasidenib, a first-in-class IDH2 inhibitor, has been approved following promising results of a phase 1-2 clinical trial in relapsed or refractory AML patients with IDH2 mutations. In this study, we described the characteristics, treatments and outcome of 75 IDH2 mutated patients both at diagnosis and relapse or refractory disease. Among the 33 relapsed/refractory AML patients with either IDH2 or IDH2, 28 (84.8%) patients received salvage therapy and 14 achieved a complete response (50%). Median duration of response was 15.2 months. Median, 1-y, 3-y and 5-y OS were 15.1 months (IQR, 4.6-37.7), 53.1% (95% CI, 33.2-69.5), 29.2% (95% CI, 12.6-48.1) and 24.4% (95% CI, 9.3-43.1), respectively. In responding patients, median OS was 37.7 months and 1-y, 3-y and 5-y OS was 85.7%, 57.1% and 47.6%, respectively. In non-responding patients, median OS was 5.0 months (IQR, 4.5-8.6) and 1-y and 3-y OS was 17.9% and 0%, respectively. Thus, a substantial number of R/R AML patients with IDH2 mutations can be salvaged by current treatments and benefit from prolonged survival. It is expected that novel targeted agents such as enasidenib will further improve efficacy and safety in the next future.
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http://dx.doi.org/10.1016/j.leukres.2019.04.010DOI Listing
June 2019
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