Hypomethylating agent therapy in myelodysplastic syndromes with chromosome 3 abnormalities

Abstract Background Abnormalities of chromosome 3 in myelodysplastic syndromes (MDS; ie, inversion 3 [inv(3)], translocation 3q [t(3q)], or deletion 3q [del(3q)] are defined as poor-risk karyotypes in the Revised International Prognostic Scoring System (IPSS-R). The objective of this study was to further define the outcomes of MDS patients with chromosome 3 abnormalities and address the impact of hypomethylating agent (HMA) therapy on this patient subset. Patients and Methods Through the MDS Clinical Research Consortium, we identified 411 patients with chromosome 3 abnormalities and MDS or oligoblastic acute myeloid leukemia (20%-30% blasts). Results Specific chromosome 3 aberrations and cytogenetic complexity were predictive of survival; patients with t(3q) and isolated chromosome 3 had improved overall survival (OS), albeit still poor, while patients with complex cytogenetics, including those with 3p abnormalities, had inferior OS. Overall response rates to HMAs among this patient population were similar to those of nonchromosome 3–MDS patients (52%, with a 25% complete remission rate) although with higher respons rates in decitabine treated patients (69% versus 45%, P = 0.008). HMA therapy improved the OS of higher-risk MDS patients compared to intensive chemotherapy (median OS of 15.5 vs 8.2 months; Pthinsp=thinsp.017). This improvement remained significant in multivariate analyses (HR 0.60; Pthinsp=thinsp.018). However, there were no chromosome 3 aberrations among this subgroup predictive of improved response rates to or survival from HMAs. Conclusion MDS patients with chromosome 3 abnormalities represent a cytogenetic cohort with poor OS, and there is an urgent need for novel therapeutic strategies.