Clinical outcomes of patients diagnosed with SETBP1 mutated myeloid neoplasms

SETBP1 mutations (m) have been previously reported in myeloid neoplasms and are associated with poor prognostic co-mutations and cytogenetic abnormalities. We retrospectively analyzed the charts of 113 patients diagnosed with myeloid neoplasms with SETBP1m. The most common diagnosis was MDS (31%). Cytogenetics were abnormal in 51 cases (46.4%), with monosomy 7 being the most common (41.1%). The most frequent co-mutations were ASXL1 (71.7%), SRSF2 (46.9%), TET2 (20.4%). Higher SETBP1m VAF was associated with proliferative features (p < 0.05). Most SETBP1m (96.5%) were in one of three hotspots (Asp868, Gly870, Ile871), with Asp868m being most frequent (51.3%). Patients with Ile871m had higher number of co-mutations (median= 4) compared to Asp868m and Gly870m (p = 0.07). On multivariate analysis, age ≥ 70 years (p = 0.004) and higher peripheral blood blasts (p = 0.02) had worse OS. Patients with Ile871m had lower OS when compared with Asp868m and Gly870m (5.5 months vs. 17.4 and 17 months, respectively, p = 0.1).