Multiple Myeloma in Adolescent and Young Adults: A SEER and CIBMTR Analysis
Authors: Gibson Steven J , Thornton Jennifer A , DeStefano Christin B 
Published: November 2020

Background
Multiple myeloma (MM) is a disease of the elderly, with less than 3% of cases diagnosed in adolescents and young adults (AYA). Data on demographics, use of autologous stem cell transplant (ASCT), second primary malignancies (SPMs) and survival are scant to non-existent in the AYA MM population. To our knowledge, this study is the first to better understand characteristics and survival trends of this unique population.
Methods
The Surveillance, Epidemiology, and End Results (SEER)-18 and Center for International Blood and Marrow Transplant Research (CIBMTR) datasets were utilized. Inclusion criteria were patients younger than 40 years old diagnosed with MM (ICD-O code 9732/3) between 2000-2017 (SEER) and 2008-2018 (CIBMTR). Variables assessed included age (&lt;30 vs. 30-39), gender, income (&lt;65K vs. ≥65K), race/ethnicity, place of residence (metropolitan vs. non-metropolitan), and year diagnosed (2000-2005 vs. 2006-2011 vs. 2012-2017). Incident SPMs were characterized as standardized incidence ratios (SIR). Analyses were conducted with STATA and data were censored at time of death or loss to follow up. Kaplan-Meier curves were generated for myeloma-specific survival (MSS). Individual variables were compared via log rank tests and Cox proportional hazard regression models. Model fit was assessed with Akaike's information criterion and Snell residuals. Assumptions of the Cox proportional hazards model were evaluated with log-time.
Results
There were 1,087 and 1,142 patients meeting criteria in SEER and CIBMTR, respectively. Median MSS was 181 months (15 years). The most common causes of death were MM (76%), SPMs (5.5%), and infection (3.6%). Statistically significant incident SPMs were lung cancers (SIR 4.94, p&lt;0.05), non-Hodgkin lymphoma (NHL) (SIR 5.28, p&lt;0.05), and acute myeloid leukemia (AML) (SIR 14.62, p&lt;0.05). Year of diagnosis strongly influenced survival. Compared to those diagnosed in 2000-2005, there was a 36% reduction in the risk of death among those diagnosed 2006-2011 (HR 0.64, 95% CI 0.49-0.82, p=0.001), and a 61% reduction among those diagnosed 2012-2017 (HR 0.39, 95% CI 0.26-0.58, p&lt;0.001). Race/ethnicity, gender, and age did not impact MSS. Among the AYA MM patients who received ASCT, notably 26% had a hematopoietic cell transplant comorbidity index (HCT-CI) of ≥ 3, nearly all received melphalan conditioning, and 80% received ASCT within the first year of diagnosis. One and four-year post-ASCT survival were 96% and 81%, respectively.
Discussion
To our knowledge, this is the first study assessing MM trends in the AYA population. Despite AYAs being underrepresented in MM clinical trials, the dramatic improvement in survival over time reflects efficacy of new drug approvals in this young population. It is also interesting that racial and socioeconomic disparities which are pervasive in the older adult MM population were not demonstrated in AYAs. AYA patients died from SPMs at rates similar to the adult MM population (3-6%), and notable incident SPMs in the AYA population were lung cancer, NHL, and AML. Also noteworthy was the high number of AYA MM patients who underwent up-front ASCT, which was nearly the same number of patients from the SEER dataset over half the amount of time. Since AYA MM patients have been underrepresented in trials utilizing ASCT, a survival benefit of ASCT in this population has not been demonstrated in the era of novel therapies. Further, given possible underlying genetic predisposition in AYA MM patients, long-term post-ASCT follow up is needed to better understand long-term toxicities including risk of hematological SPMs.
Disclosures
The findings and opinions contained herein are those of the authors and do not represent the views/opinions of the United States Air Force, Walter Reed National Military Medical Center, David Grant Medical Center, Department of Defense, or the Center for International Blood and Marrow Transplant Research (CIBMTR).

Disclosures
No relevant conflicts of interest to declare.