Molecular predictors of response in patients with myeloid neoplasms treated with lenalidomide

Lenalidomide use in myelodysplastic syndromes: Insights into the biologic mechanisms and clinical applications

“…Beyond 5q−, several clinical as well as genetic markers have the potential to provide better guidance to clinicians in predicting responsiveness to lenalidomide (Table ). Advanced disease, male sex, complex cytogenetics, cytopenias, and a higher percentage of bone marrow blasts are all associated with worse response to lenalidomide; however, no clinical marker alone is able to consistently predict a response to lenalidomide . Therefore, current research efforts are focusing on identifying a genetic signature predicting response to lenalidomide.…”

Successful lenalidomide treatment in high risk myelodysplastic syndrome with germline DDX41 mutation

“…2 DDX41 knockdown resulted in increased proliferation and differentiation block in pre-clinical models. 1,5 Here, we report a case of high risk MDS (MDS with excess blasts-2 (MDS-EB-2) with a germline DDX41 mutation, who responded to single agent lenalidomide as initial therapy. 1 Other acquired somatic mutations in other genes are relatively uncommon.…”

“…2 The median age of onset of MDS/AML for germline DDX41 mutation carriers is 62 years; near the average age incidence in de-novo MDS or AML. 5 In a larger single institution retrospective cohort evaluation, next-generation targeted deep sequencing of 139 patients with MDS, or other myeloid malignancies, was analyzed to predict lenalidomide responsiveness. Note, DDX41 is located on chromosome 5q35, and notably is deleted in only 25% of MDS cases with del(5q) that is usually responsive to lenalidomide therapy.…”

“…1,4 Interestingly, in several retrospective analyses, patients with DDX41 mutations without isolated del(5q) have reportedly demonstrated better responses to lenalidomide, mostly in low risk MDS disease. 1,5 Here, we report a case of high risk MDS (MDS with excess blasts-2 (MDS-EB-2) with a germline DDX41 mutation, who responded to single agent lenalidomide as initial therapy. Our patient is a 62-year-old man who presented to our leukemia clinic for evaluation of persistent pancytopenia with concern for MDS.…”

“…1 Moreover, among seven patients with heterozygous DDX41 mutations or deletions, 57% of patients responded to lenalidomide alone. 5 In a larger single institution retrospective cohort evaluation, next-generation targeted deep sequencing of 139 patients with MDS, or other myeloid malignancies, was analyzed to predict lenalidomide responsiveness. 6 The combination of DDX41 mutations and normal cytogenetics was associated with increased responsiveness to lenalidomide, with a prediction accuracy of 82%.…”