Background According to OMS-2016, myelodysplastic syndrome (MDS) associated with del(5q) is manifested by a transfusion-dependent progressive bone marrow failure, with Lenalidomide acting as the intended drug to treat this syndrome.

Purpose To analyse the clinical impact of the directed risk-stratification therapy and to evaluate the clinical benefit associated with the discontinuation of the Lenalidomide treatment due to side effects or intolerance.

Material and methods Three-year prospective observational study on 69 cases of MDS in a third-level hospital, 17 of them with del(5q). Mutational profile analysis using a Next Generation Sequencing (NGS) on a panel of 28 genes mutated in haematologic malignancies prior to Lenalidomide treatment decision-making, with TP53 mutation as ultra-high-risk profile for discouraging its use. Variables considered: beginning of treatment, Lenalidomide mean dose, ending of treatment and beginning of discontinuation, side effects, time after discontinuation, evaluation of the drug withdrawal response and cost savings.

Results Sixty-nine MDS cases were analysed by NGS. Mutational risk profile: high (six), low (21), intermediate (18), very high (seven) and very low (17). Seventeen cases were detected as MDS associated with del(5q) and five of them showed positive TP53 mutation and were treated with hypomethylating agents instead of Lenalidomide. Seven of them showed DNMT3A, ASXL1, SF3B1 and TET2 mutations. Eleven patients were treated with Lenalidomide, the treatment was discontinued in six of them due to side effects and the dose reduced in three cases due to intolerance. Reported side effects: Grade 4 neutropaenia, rhabdomyolysis, erythematous reactions and haemolytic crisis. All patients in which Lenalidomide was discontinued, maintained complete haematological and cytogenetic response, reaching a mean monitoring time of 12 months since the withdrawal of Lenalidomide. The cost saving associated with the discontinuation of Lenalidomide 10 mg was €48 000 per patient per year.

Conclusion The use of NGS permits the selection of the mutational profile of each patient, resulting in a change in therapeutic decision-making, the selection of more cost-effective drugs and a directed and personalised treatment. Discontinuation of Lenalidomide, due to side effects or intolerance, involves a clinical benefit to those patients who maintain a complete haematological response after interruption of the treatment.

Reference and/or acknowledgements Chesnais, et al. Blood 2016;127:749–60.

No conflict of interest.