Abstract Background: Age is an important prognostic factor for multiple myeloma (MM). We evaluated the influence of age on the clinical presentation and outcomes among newly diagnosed patients with MM to optimize risk stratification. Methods: In 850 patients with first primary confirmed MM prospectively enrolled in the Integrative Molecular And Genetic Epidemiology (IMAGE) study (2009-2020), we evaluated the presence of diagnostic myeloma-defining events (MDE), progression free survival (PFS) and overall survival (OS) by young age at diagnosis (≤50 years). We evaluated the association of young age with the prevalence of diagnostic MDE, clinical features and chromosomal abnormalities using the prevalence odds ratio (OR) and corresponding 95% confidence interval (CI) calculated from multivariable logistic regression. Median PFS and OS were graphically examined using Kaplan-Meier survival curves with log-rank tests used to compare survival by diagnostic age group. Risks of disease progression and all-cause mortality were estimated using hazard ratios (HR) and corresponding 95% CI calculated from multivariable Cox proportional hazard models. Results.: Of the 850 patients, 15.4% were diagnosed at ≤50 years of age, 54% were male and 40% self-identified as Black. Compared to patients diagnosed with MM over the age of 50, young patients were more likely to self-identify as Black (59.5% vs 40.5%; P<0.0001) and to report a negative smoking history (66.2% v 56.4%; P=0.01), and less likely to present with age-dependent comorbidities including hypertension, hyperlipidemia and diabetes mellitus type II (P≤0.0001). In multivariable analyses, young patients, compared to older patients, were more likely to present at diagnosis with higher median percent bone marrow plasma cells (70% v 55%; P=0.02) and to undergo autologous stem cell transplant (ASCT) as part of their first-line treatment (82.0% v 67.6%; P=0.01) after controlling for sex, race, body mass index, smoking status and comorbidities. We did not observe significant associations of young age with the prevalence of any other MDE, clinical feature or chromosomal abnormality evaluated. The median OS was 106.9 months (range, 0.23-356.1). OS was significantly longer in young patients with MM compared to patients aged greater than 50 years (159 v 99 months, respectively; P<0.001) leading to a suggestive 1.5-fold decreased risk of mortality among younger newly diagnosed patients (HR=0.67, 95% CI 0.39-1.14; P=0.14) after adjusting for sex, International Staging System-stage, adverse cytogenetic abnormalities, and ASCT. We did not observe associations with age and PFS (P=0.81). Conclusions: Findings suggest that newly diagnosed younger patients with MM are more likely to self-identify as Black, present with more bone marrow plasma cells, have less age-dependent comorbidities, and undergo ASCT leading to a suggestive survival advantage. Citation Format: Krystle L. Ong, Kevin D. Arnold, Gayathri Ravi, Luciano J. Costa, Elizabeth E. Brown. Influence of young age at diagnosis on the clinical presentation of disease and survival among patients with multiple myeloma [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 848.