<h3>Background</h3> Chromosome 1 abnormalities (C1A) are frequently identified in multiple myeloma (MM). We assessed impact of C1A in a post hoc analysis of E1A11 trial. <h3>Methods</h3> E1A11 randomized newly diagnosed (ND) MM patients (pts) with traditional ‘standard risk' features or t(4;14), not intended for upfront transplant, to bortezomib (V) or carfilzomib (K), in combination with lenalidomide (R) and dexamethasone (d), followed by indefinite or 2-year (y) R maintenance. Impact of C1A and ultra-high risk (UHR) MM [≥2 of the following: +1q [gain1q (3 copies) or amplification (amp)1q21 (≥4 copies)], deletion (del)1p and t(4;14)], was assessed. <h3>Results</h3> Of 1087 pts, 912 were evaluated for + 1q (gain1q or amp1q) and 774 for del1p. Gain1q, amp1q and del1p were noted in 23%, 7.5% and 9% pts, respectively. Best responses to VRd or KRd within each response category were similar, irrespective of +1q/del1p status. Within each arm, progression-free survival (PFS) was inferior for pts with +1q versus (v) pts without +1q; median 29 v 42 months (m) for both arms [VRd, HR 1.51 p 0.011; KRd, HR 1.63, p 0.002]. Corresponding 3y overall survival (OS) rates on VRd were 74 v 86% (HR 1.47, p 0.069) and 82 v 88% (HR 1.34, p 0.185) on KRd. Regarding copy number, pts with gain1q v those without +1q had inferior PFS with both VRd (median 29m, HR 1.59, p 0.012) and KRd (median 33m, HR 1.41, p 0.051). OS rates with gain1q were inferior within VRd arm only (3y 71%, HR 1.78, p 0.014; KRd 3y OS 89%, HR 1.02, p 0.93). By contrast, pts with amp1q, v pts without +1q, had inferior outcomes with KRd (median PFS 24m, HR 2.37, p<0.001; 3y OS 62%, HR 2.43, p 0.008) but not with VRd: median PFS 32m, HR 1.43; p 0.186; 3y OS 75%, HR 1.29; p 0.48). Pts with del1p, v those without del1p, had inferior PFS (median 29 v 39m; HR1.49, p=0.042) and OS rates (3y 74 v 85%, HR 2.03; p 0.003) in the entire cohort. Within KRd arm, the respective OS rates were comparable (3y, 87 v 86%, HR 1.10, p 0.818). By contrast, pts with del1p on VRd had inferior OS (3y 60 v 84%, HR 3.30, p<0.001). UHR MM pts had worst outcomes (median PFS, 20 v 38m, HR 2.01, p<0.001; 3y OS, 68 v 85%, HR 1.99, p 0.004). However, OS for UHR MM pts on KRd was similar to that of pts without UHR MM (3-yr, 87 v 86%, HR 0.95, p 0.902; VRd 3-yr, 45 v 84%, HR 4.15, p<0.001). Analyses of treatment effect within subgroups showed superiority of KRd over VRd for OS among pts with gain1q [HR 0.50 (0.28-0.90)], del1p [HR 0.34 (0.13-0.89)] and UHR MM [HR 0.18 (0.07-0.51)], but not amp1q [HR 1.56 (0.64-3.78)]. <h3>Conclusion</h3> Gain1q or amp1q portends poor outcome among NDMM pts treated with either VRd or KRd. Specifically, pts with amp1q as a sole high-risk abnormality have distinctly poor outcomes with KRd. By contrast, KRd, but not VRd, appears to abrogate the adverse impact of del1p. Given the limitations of the trial design and post hoc subset analyses, longer follow up and confirmatory studies are warranted for definitive conclusions.