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Lenalidomide is approved for the treatment of transfusion-dependent (TD) del(5q) myelodysplastic syndromes (MDS). However, few data are available in patients with transfusion-independent (TI) del(5q) MDS. In the first, observational, part of this 2-part study, we assessed the impact of transfusion dependence on overall survival (OS) and non-leukemic death in untreated del(5q) MDS patients who were TD (n = 136), TI with hemoglobin (Hb) ≥10 mg/dL (n = 88), or TI with Hb <10 mg/dL (n = 96). In the second, interventional, part we assessed the quality-of- life (QoL) benefits and clinical efficacy of lenalidomide (10 mg/day) in 12 patients with TI del(5q) MDS and Hb <10 mg/ dL. In the untreated population, OS was significantly longer in TI than in TD patients (TI [Hb ≥10 g/dL], 108 months; TI [Hb <10 g/dL], 77 months; TD, 44 months). Transfusion dependence also negatively impacted non-leukemic death rates. In the interventional part of the study, baseline Hb levels were found to correlate significantly with physical (R = 0.666, P = 0.035) and fatigue (R = 0.604, P = 0.049) QoL scores. Median physical QoL scores improved significantly after 12 weeks’ treatment with lenalidomide (+12.5; P = 0.020). Evaluable TI patients experienced early increases in Hb levels, and all attained an erythroid response. Our findings suggest that TI patients with moderate anemia may benefit from early treatment with lenalidomide. [ABSTRACT FROM AUTHOR]

Background: Haploinsufficiency of the ribosomal protein S14 RPS14 gene, located in the common deleted region of chromosome 5q, is a potential causal factor of 5q− syndrome. Lenalidomide elicits high response rates and morphological improvements in myelodysplastic syndrome (MDS) patients with chromosome 5q deletion [del(5q)]. Methods: To further evaluate the role of RPS14, its transcription was tested in bone marrow cells from 17 patients with International Prognostic Scoring System defined Low- or Intermediate-1-risk MDS with del(5q) as a single or additional cytogenetic abnormality receiving treatment with lenalidomide. Results: After 12 wk of lenalidomide treatment, erythroid responses were observed in all cases with an increase in hemoglobin levels of 2.7 ± 2.5 g/dL (up to a mean 11.8 ± 1.9 g/dL; P = 0.001). Before treatment, RPS14 expression levels were under-expressed in 15 patients with respect to normal controls. After 12 wk of lenalidomide treatment, all patients had an erythroid response. There was a significant increase in median RPS14 expression from baseline 0.01 (IQR 0.05–0.31) to 12 wk 204.71-fold (2.86–446.32; P < 0.0001). Conclusions: These observations in the patient setting support the importance of RPS14 in the pathogenesis of MDS with del(5q). [ABSTRACT FROM AUTHOR]