Risk stratification systems and outcome. PFS as defined by the different risk stratification systems. (A) Ultrahigh risk defined by the presence of >1 adverse lesion (t(4;14), t(14;16), t(14;20), del(17p), and gain(1q)) in the analysis of 869 cases from the MRC Myeloma IX trial (published 2011). Reprinted from Boyd et al²⁴  with permission. (B) Ultrahigh risk defined by the R-ISS (low-risk R-ISS group I [ISS stage I with no high-risk CA (del(17p) and/or t(4;14 and/or 14;16)) and normal LDH level] to high-risk R-ISS group III [ISS stage III and high-risk CA or high LDH level]) in a pooled study of 4445 patients with newly diagnosed multiple myeloma from 11 clinical studies (published 2016). Reprinted from Palumbo et al⁵⁵  with permission. (C) Ultra high-risk defined as double-hit myeloma (either loss of both alleles of TP53 [by mutation, deletion or both] or with 2 extra copies of 1q, resulting in amplification rather than a single gain) by incorporating NGS data in the Myeloma Genome Project analysis of 784 patients (published 2018). Reprinted from Walker et al.³²