Background: Recurrent somatic mutations in SF3B1 have been identified in patients with myelodysplastic syndromes (MDS) and are associated with ring sideroblasts (RS) and relatively favorable clinical outcomes. The 2016 World Health Organization classification categorizes patients with ≥ 5% RS and SF3B1 mutation as MDS-RS, in contrast to its prior MDS-RS classification (≥ 15% RS, no genotyping data). Treatment responses in MDS patients with mutated SF3B1 are not well described.
Patients and methods: Patients with MDS and known SF3B1 mutational status were identified from MDS Clinical Research Consortium institutions and grouped when possible as 5% to 15% or ≥ 15% RS. Patients with wild-type versus mutated SF3B1 were matched 2:1 to analyze treatment response.
Results: Of 471 patients identified, 16% showed SF3B1 mutation. More patients with mutated SF3B1 were lower-risk MDS. We found that 50% were RS-positive compared to 19% of wild-type patients (P < .001). Having the mutation was associated with better overall survival (hazard ratio = 0.48, P = .001) and longer leukemia-free survival (hazard ratio = 0.5, P < .005). Patients with RS and the mutation had the best outcome. Regarding treatment response, 14 (35%) of 40 erythroid-stimulating agent-treated patients with mutation experienced response versus 9 (16%) of 56 wild-type patients (P = .032), with no differences in response to hypomethylating agents or lenalidomide.
Conclusion: SF3B1 mutations in MDS are commonly associated with RS and show better outcomes, with mutated/positive RS presence being significantly better than isolated RS or presence of mutation or neither. Patients with mutation showed better responses to an erythroid-stimulating agent. A new categorization incorporating SF3B1 mutation status, regardless of RS percentage, shows clinical value.
Keywords: Outcome; Prognosis; Treatment; WHO classification.
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