Background: Effective AML maintenance treatment (Tx) should decrease the risk of relapse and prolong survival without compromising HRQoL. In the placebo (PBO)-controlled phase III QUAZAR AML-001 trial (NCT01757535), CC-486, an oral hypomethylating agent, provided significant improvements in overall (OS) and relapse-free survival (RFS) in patients (pts) with AML in first remission following IC. Here we present pt-reported HRQoL outcomes from that study. Methods: Eligible pts were ≥ 55 yrs of age with intermediate- or poor-risk cytogenetics and ECOG PS ≤ 3, and in CR/CRi after IC ± consolidation. Pts were randomized 1:1 to CC-486 300 mg or PBO QD on days (d) 1–14 of 28d Tx cycles. HRQoL was assessed by FACIT-Fatigue scale and EQ-5D-3L health utility index, completed on d1 of each cycle and at end of Tx (EOT). Endpoints include Tx differences in mean changes from baseline (BL), and proportions of pts with clinically meaningful change from BL (improvement, no change, deterioration). Evaluable pts had an HRQoL assessment at BL and ≥ 1 post-BL visit. Stratified ANCOVA models included Tx and BL scores as covariates. Results: In all, 225/238 pts (95%) in the CC-486 arm were evaluable for FACIT-Fatigue and EQ-5D-3L, and 219/234 pts (94%) in the PBO arm were evaluable for FACIT-Fatigue and 217 (93%) for EQ-5D-3L. Pt characteristics were comparable between Tx arms. Most pts (61%) were 65-74 yrs of age. Median number of CC-486 Tx cycles was 12 and PBO cycles was 7. Compliance rates were > 95% at BL and remained high (> 85%) at all post-BL visits except for EOT. At BL, pts in both Tx arms had comparable low levels of fatigue and generally good HRQoL relative to an age-matched general population. There were no meaningful differences between CC-486 and PBO in mean changes from BL in FACIT-Fatigue or EQ-5D-3L scores at any post-BL visit. There was no statistically significant difference between Tx arms in proportion of pts with a clinically meaningful deterioration in FACIT-Fatigue score at any post-BL visit except at cycle 29 (likely due to chance; no adjustment made for multiple testing), or in EQ-5D-3L at any visit. Median time to deterioration was not significantly different between CC-486 and PBO on the FACIT-Fatigue scale (41 vs 44 weeks, respectively; P = 0.70) or the EQ-5D-3L (200 vs 164 weeks; P = 0.63). Conclusions: HRQoL and low levels of fatigue were preserved with CC-486 maintenance Tx. CC-486 significantly improved OS and RFS while maintaining HRQoL comparable to PBO. Clinical trial information: NCT01757535.