OS of patients with SF3B1-mutant MDS according to additional somatic mutations. (A) OS by isolated SF3B1 mutation (n = 201, blue curve) vs SF3B1 mutation associated with additional somatic mutations within SF3B1-mutated MDS without excess blasts (SF3B1 plus 1 additional mutation, n = 192, red curve; 2 additional mutations, n = 66, green curve; ≥3 additional mutations, n = 23, purple curve) (including patients sequenced for all of the following 15 genes: SF3B1, TET2, DNMT3A, SRSF2, ASXL1, RUNX1, TP53, EZH2, JAK2, U2AF1, IDH1, IDH2, CBL, NRAS, and ETV6). (B-C) OS and cumulative incidence of AML evolution of SF3B1-mutated MDS without excess blasts according to RUNX1 mutation status (mutated, n = 21, red curve; unmutated, n = 505, blue curve) (P < .001). Cumulative incidence of AML evolution was estimated with a competing risk approach, considering death for any cause as a competing event. (D) OS of SF3B1-mutated MDS without excess blasts according to EZH2 mutation status (mutated, n = 20, red curve; unmutated, n = 499, blue curve) (P = .003).