Comutational burden and NRAS mutations are associated with lack of response. (A) Scatter plot showing mean and standard deviation of number of mutations found per patient, separated by response. P < .001, comparing the difference between nonresponders and either responders (R: CRi, CRp, MLFS, or PR) or patients achieving a CR. (B) Pie charts of response assessment and ORR (patients achieving CR, CRi, CRp, MLFS, or PR) in patients with the lowest third number of comutations (≤3 mutations) and the highest third (≥6 mutations). (C) Pie chart indicating proportion of responders and nonresponders in the 14 efficacy evaluable patients with NRAS comutations (mNRAS), specifically at G12, G13, and Q61. (D) Number of mutations found per patient separated by the presence of G12, G13, or Q61 mutant mNRAS, indicating that patients with mNRAS at G12, G13, or Q61 have an increased mutational burden in this cohort. The only mNRAS⁺ patient to achieve a CR is highlighted in green. (E) Dot plot of mIDH2 (blue) and mNRAS (red) VAF in the same patient in the 14 efficacy-evaluable patients with NRAS comutations specifically at G12, G13, and Q61. NRASwt, NRAS wild-type.