Background: Pts with AML in RCTs often do not reflect the population seen in clinical practice due to strict eligibility criteria. This study evaluated criteria from a recent RCT of non-IC against a broad cohort of real-world pts with AML from the Connect^® Myeloid Disease Registry (NCT01688011). Methods: Pts were stratified into 3 groups based on the non-IC phase 3 VIALE-A trial eligibility criteria: 1) “eligible” pts who would have met all VIALE-A inclusion criteria; 2) “unfit” pts who would have been ineligible for VIALE-A due to ≥ 1 of the following: abnormal liver/kidney function, high ECOG, recent prior malignancy, comorbidities score ≥ 2 by ACE-27, hepatic grade ≥ 1, AIDS grade ≥ 1; 3) “fit” pts who would have been ineligible for VIALE-A because they would have qualified for IC (defined as: ≤ 74 y of age, low ECOG, no apparent cardiovascular/renal comorbidities, and did not meet any criteria in #2). Baseline characteristics were summarized by eligibility group. Overall survival (OS) by group was estimated using the Kaplan–Meier method. Induction regimens were categorized as IC (any regimens containing 7+3, MEC, CLAG, FLAG) or venetoclax (VEN)-based. Hazard ratios (HRs) for induction regimens among each group were estimated using Cox models adjusted for age, ELN risk, ECOG, frailty score, and comorbidity index. Results: Of 734 enrolled pts with AML (Dec 2021), most were male (61%) and white (84%); median age 71 y (range 55–97). Only 26% of pts (n = 192) were eligible for a non-IC RCT, 45% (n = 327) were ineligible due to unfitness, and 29% (n = 215) were ineligible due to overall fitness. The main reason for non-IC RCT ineligibility was high overall comorbidity grade (n = 265 [36%]). Fit pts intended to undergo transplant more often compared with unfit pts. Median OS for eligible, unfit, and fit pts were 14, 10, and 22 months, respectively. Among unfit pts, those receiving IC had significantly longer OS compared with pts receiving a VEN-based regimen (median OS 14 vs 6 months, respectively; HR: 0.51, 95% CI: 0.27–0.98, P = 0.042; Table). Eligible pts who received IC tended to have shorter median OS (13 months) vs pts who received VEN-based therapies (23 months; not sig.). Conclusions: The majority of pts with ND AML in the Registry would have been ineligible for a non-IC RCT due to being too fit or unfit. Pts ineligible for an RCT due to unfitness but who received IC maintained an OS benefit vs those receiving VEN-based therapies. This analysis suggests that non-IC RCTs may be excluding pts who appear unfit but can potentially tolerate IC and experience improved survival outcomes. Clinical trial information: NCT01688011.

*P< 0.05; ^aNot estimated due to small sample size.