Abstract
While lenalidomide (LEN) is the standard of care for the lower-risk myelodysplastic syndromes (MDS) patients with deletion 5q, 35% will not respond to or do not tolerate the drug. Moreover, most of the patients will lose their response after a few years. Defining the outcome of patients with LEN failure and determining the impact of subsequent therapies is therefore important to develop alternative strategies. Based on an international collaboration, we were able to compile a total of 392 patient cases of lower-risk MDS patients with 5q deletion and to analyze their outcome after failure of lenalidomide. The median survival following LEN failure was 23 months. We observed a negative impact on survival of advanced age, higher bone marrow blast count at LEN initiation, progression after LEN failure, and unfavorable cytogenetics. Among the treatment strategies, we observed a relatively prolonged survival of patients treated subsequently with hypomethylating agents and only a limited impact on survival of allogeneic transplantation. In conclusion, our work stresses the relatively short survival of this group of patient and defines the expected baseline for the needed future investigations in this group of patients.
Highlights
Myelodysplastic syndromes (MDS) are a heterogeneous group of diseases characterized by ineffective hematopoiesis, peripheral blood cytopenias, and a risk of evolution to acute myeloid leukemia [1]
As expected for a population defined by the presence of del 5q, the patients’ characteristics were slightly different from the general population of MDS patients
13 patients (6%) were treated with other modalities (Thalidomide (n=4), Antithymocyte globulin (n=3), danazol (n=1), ruxolitinib (n=1), clinical trials (n=4)) and those numbers were too low to evaluate outcome. This is the first large study focused on the outcome of MDS patients with deletion 5q after LEN failure
Summary
Myelodysplastic syndromes (MDS) are a heterogeneous group of diseases characterized by ineffective hematopoiesis, peripheral blood cytopenias, and a risk of evolution to acute myeloid leukemia [1]. Over the last decade, hypomethylating agents [24] (HMA) and lenalidomide [5, 6] (LEN) changed therapeutic approaches for MDS, offering for the first time treatments able to durably correct cytopenias and www.impactjournals.com/oncotarget potentially to prolong survival. LEN has been tested in higher-risk disease with del 5q as single agent [14], in combination with HMA [15, 16], or with chemotherapy [17]; a more limited success was observed. LEN has obtained Food and Drug Administration approval for transfusion-dependent anemia due to low- or intermediate-1-risk MDS associated with a del 5q with or without one additional cytogenetic abnormality, whereas the European Medicine Agency has restricted approval for those with isolated del 5q cytogenetic when other therapeutic options are insufficient or inadequate. The drug is still undergoing additional monitoring due to the lack of sufficient follow-up data
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