A randomized phase 3 study of lenalidomide versus placebo in RBC transfusion-dependent patients with Low-/Intermediate-1-risk myelodysplastic syndromes with del5q

Fenaux, Pierre; Giagounidis, Aristoteles; Selleslag, Dominik; Beyne‐Rauzy, Odile; Mufti, Ghulam J.; Mittelman, Moshe; Muus, Petra; Boekhorst, Peter te; Sanz, Guillermo; Cañizo, Consuelo del; Guerci‐Bresler, Agnès; Nilsson, Lars; Platzbecker, Uwe; Lübbert, Michael; Quesnel, Bruno; Cazzola, Mario; Ganser, Arnold; Bowen, David; Schlegelberger, Brigitte; Aul, Carlo; Knight, Robert D.; Francis, John L.; Fu, Tommy; Hellström‐Lindberg, Eva

doi:10.1182/blood-2011-01-330126

Cited by 437 publications

(440 citation statements)

References 23 publications

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“…Owing to the fact that AML evolution cannot be suppressed by treatment with lenalidomide and the risk of progression was lower in responders, 32,33 there might be underlying unknown molecular mechanisms that promote or allow progression. As the response to Lenalidomide very often occurs very quickly during the first 1 --4 months of treatment, non-responders should discontinue the drug and move to other therapeutic modalities.…”

Section: Discussionmentioning

confidence: 99%

Survival, prognostic factors and rates of leukemic transformation in 381 untreated patients with MDS and del(5q): A multicenter study

et al. 2012

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Myelodysplastic syndromes (MDS) with del(5q) are considered to have a benign course of the disease. In order to address the issue of the propensity of those patients to progress to acute myeloid leukemia (AML), data on 381 untreated patients with MDS and del(5q) characterized by low or intermediate I International Prognostic Scoring System (IPSS) risk score were collected from nine centers and registries. Median survival of the entire group was 74 months. Transfusion-dependent patients had a median survival of 44 months vs 97 months for transfusion-independent patients (Po0.0001). Transfusion need at diagnosis was the most important patient characteristic for survival. Of the 381 patients, 48 (12.6%) progressed to AML. The cumulative progression rate calculated using the Kaplan --Meier method was 4.9% at 2 years and 17.6% at 5 years. Factors associated with the risk of AML transformation were high-risk World Health Organization adapted Prognostic Scoring System (WPSS) score, marrow blast count 45% and red-cell transfusion dependency at diagnosis. In conclusion, patients with MDS and del(5q) are facing a considerable risk of AML transformation. More detailed cytogenetic and molecular studies may help to identify the patients at risk of progression.

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Section: Discussionmentioning

confidence: 99%

Survival, prognostic factors and rates of leukemic transformation in 381 untreated patients with MDS and del(5q): A multicenter study

et al. 2012

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“…The MM-017 (n = 15) [1] and MDS-007 (n = 11) [2] studies, which are clinical studies conducted on Japanese patients, found one and five cases of lenalidomide-induced eosinophilia, respectively. However, among clinical studies conducted in countries other than Japan, the MDS-001 study (n = 43) [6] and a pilot study of concurrent lenalidomide and radiotherapy for glioblastoma multiforme (n = 23) [7] found three cases and one case, respectively, of lenalidomide-induced eosinophilia, whereas the MM-009/010 (n = 353) [3,4] and MDS-004 (n = 69) [5] studies found no such cases. Studies other than clinical studies have also reported lenalidomide-induced eosinophilia: 5 cases in the special drug use-results survey involving 2,449 patients who had received lenalidomide from July 2010 to February 2013 in Japan [8] and four cases from case reports (Table 3).…”

Section: Discussionmentioning

confidence: 99%

“…Eosinophilia during treatment with lenalidomide is rare, with only 19 cases reported to date [1][2][3][4][5][6][7][8][9][10][11]. Of these, only five patients were under treatment with the drug for multiple myeloma.…”

Section: Introductionmentioning

confidence: 99%

Patient with Refractory Multiple Myeloma Developing Eosinophilia after Lenalidomide Treatment and Lung Cancer 9 Months Later: Case Report and Review of the Literature

Sekiguchi

Shimada

Imai

et al. 2014

Indian J Hematol Blood Transfus

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“…The molecule was originally associated with its responsiveness against MDS patients with a chromosomal aberration of −5q [63], where 50% of patients showed cytogenetic remission [64]. DDX41 does not lie within the commonly deleted region of 5q [65]; however, recently it was shown that MDS patients with DDX41 mutations or low gene expression respond better to treatment with lenalidomide than MDS patients without DDX41 alteration [19].…”

Section: Future Handling and Treatment Of Ddx41-associated Myeloid Mamentioning

confidence: 99%

Myeloid neoplasms with germline DDX41 mutation

et al. 2017

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to DDX41 mutation and highlights how each of these suggest potential therapeutic opportunities through the use of pathway-specific inhibitors.Keywords DDX41 · Myeloid malignancy · Myelodysplastic syndrome · Acute myeloid leukemia · Germline mutation · Predisposition Familial predisposition to myeloid neoplasmsMyeloid neoplasms are a heterogeneous group of diseases encompassing myeloproliferative neoplasms (MPN), myelodysplastic syndromes (MDS) and acute myeloid leukemia (AML), all of which are characterized by abnormal growth and development of cells of the myeloid blood lineage. These disease groups can be further sub-categorized by a number of different morphological and molecular approaches which may correlate with responses to specific treatments [1]. AML and MDS Abstract Recently, DDX41 mutations have been identified both as germline and acquired somatic mutations in families with multiple cases of late-onset myelodysplastic syndrome (MDS) and/or acute myeloid leukemia. The majority of germline mutations are frameshift mutations suggesting loss of function with DDX41 acting as a tumor suppressor, and there is a common somatic missense mutation found in a majority of germline mutated tumors. Clinically, DDX41 mutations lead to development of high-risk MDS at an age similar to that observed in sporadic cohorts, presenting a unique challenge to hematologists in recognizing the familial context. Functionally, DDX41 has been shown to contribute to multiple pathways and processes including mRNA splicing, innate immunity and rRNA processing. Mutations in DDX41 result in aberrations to each of these in ways that could potentially impact on tumorigenesis-initiation, maintenance or progression. This review discusses the various molecular, clinical and biological aspects of myeloid malignancy predisposition due

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A randomized phase 3 study of lenalidomide versus placebo in RBC transfusion-dependent patients with Low-/Intermediate-1-risk myelodysplastic syndromes with del5q

Cited by 437 publications

References 23 publications

Survival, prognostic factors and rates of leukemic transformation in 381 untreated patients with MDS and del(5q): A multicenter study

Survival, prognostic factors and rates of leukemic transformation in 381 untreated patients with MDS and del(5q): A multicenter study

Patient with Refractory Multiple Myeloma Developing Eosinophilia after Lenalidomide Treatment and Lung Cancer 9 Months Later: Case Report and Review of the Literature

Myeloid neoplasms with germline DDX41 mutation

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