Lenalidomide in lower‐risk myelodysplastic syndromes with karyotypes other than deletion 5q and refractory to erythropoiesis‐stimulating agents

Abstract

SummaryLenalidomide (LEN) has been shown to yield red blood cell (RBC) transfusion independence in about 25% of lower risk myelodysplastic syndromes (MDS) without del(5q), but its efficacy in patients clearly refractory to erythropoiesis‐stimulating agents (ESA) is not known. We report on 31 consecutive lower‐risk non‐del(5q) MDS patients with anaemia refractory to ESA and treated with LEN in a compassionate programme, 20 of whom also received an ESA. An erythroid response was obtained in 15 patients (48%), including 10 of the 27 (37%) previously transfusion‐dependent (RBC‐TD) patients, who became transfusion‐independent (RBC‐TI). Nine of the responders relapsed, whereas 6 (40%) were still responding and transfusion‐free after 11+–31+ months. Median response duration was 24 months. The erythroid response rate was lower in refractory cytopenia with multilineage dysplasia (27% vs. 60%) and tended to be higher in patients treated with LEN + ESA (55% vs. 36%). Response duration was significantly longer in responders who obtained RBC‐TI and in patients treated with LEN after primary resistance to ESA. The main toxicity of LEN was cytopenias. We confirm that, in a patient population of lower risk MDS without del 5q clearly resistant to ESA, LEN is an interesting second line therapeutic option. Its combination with ESAs in this context warrants prospective studies.

Current therapy of myelodysplastic syndromes

“…An erythroid response rate of 48% and a transfusion-independence rate of 37% have been reported in a retrospective study of 31 consecutive ESA-refractory anemic patients with LR-MDS who lacked 5q–, with a median response duration of 24 months [74]. Therefore lenalidomide can be considered in some transfusion-dependent patients with LR-MDS without 5q– with primary or secondary resistance to ESA therapy, or as upfront therapy in those with high endogenous serum erythropoietin levels who are less likely to respond to ESA therapy [39].…”

Effect of lenalidomide treatment on clonal architecture of myelodysplastic syndromes without 5q deletion

“…7,8 In this context, the addition of high doses of epoetin was suggested to increase the hematologic response to lenalidomide. 9,10 Predictive biomarkers of response are needed to guide the use of lenalidomide (with or without ESAs) in these patients, and recurrent somatic mutations could be such molecular predictors. The present study investigated mutations in 26 selected genes [11][12][13] in a cohort of 94 non-del(5q) International Prognostic Scoring System low and intermediate-1 MDS patients who received lenalidomide with or without epoetin b (EPO) as second-line treatment of their ESA-resistant anemia.…”

Myelodysplastic Syndromes and Acute Myeloid Leukemia in the Elderly

“…Myelosuppression is the primary toxicity of lenalidomide often requiring dose reduction or dose delay. Studies suggest treatment with lenalidomide may also benefit patients with low-risk MDS without 5q deletion and it can be considered an option for these patients as well if they are transfusion dependent 23 .…”