Treatment Advances for Multiple Myeloma Have Disproportionally Benefited Patients Who Are Young, White, and Have Higher Socioeconomic Status
Authors: Fiala Mark A. , Keller Jesse , Stockerl-Goldstein Keith E. , Tomasson Michael H. , Vij Ravi , Wildes Tanya M 
Published: October 2019

Abstract
Background: The use of autologous stem cell transplants (ASCT) for multiple myeloma (MM) has greatly improved overall survival (OS), however, not all patients have benefited equally. Several studies have indicated that patients over the age of 65 or 70 at diagnosis had no immediate improvement in OS following the use of ASCT for MM, which is intuitive as ASCT was not covered by Medicare until 2001 and today is still often reserved for patients under 70. In addition, Waxman, et al (Blood, 2010) reported that ASCT for MM, resulted in nearly a two-fold improvement in OS in white patients compared to black patients. This suggests that white patients had better access to ASCT as retrospective studies of MM patients who undergo ASCT have failed to show an OS difference between the two races. Disparities in the OS benefit of ASCT among patients of different socioeconomic groups have not been reported on to date. It is also unclear if these disproportional improvements in outcomes have continued following the approvals of bortezomib and lenalidomide.
Methods: Using the SEERStat software, we extracted the case listings of 85,115 patients diagnosed with MM from 1973 through 2010 in Surveillance Epidemiology and End Results (SEER)-18 registries database based on the November 2012 submission. Children (under 18 years old) were excluded. Autopsy or death certificate only cases were excluded. Patients identified as any race other than white or black were excluded. Patients were followed for OS through December 2011.
Patients were divided into three cohorts based on the year of diagnosis, era 1 those diagnosed from 1973 to 1994, era 2 those diagnosed from 1995-2002 (to coincide with ASCT), and era 3 those diagnosed from 2003-2010 (to coincide with bortezomib’s approval). Socioeconomic status (SES) was approximated by median household income (MHI) of each patient’s county of residence from the 1990 US census; patients were divided into tertiles within their era of diagnosis based on MHI and classified as low-SES, middle-SES, or high-SES.
Results: 78,681 patients were eligible for analysis. The median age at diagnosis was 70 years (range 18-85+); 54% were male; 18% were black. The median follow-up was 22 months (range 0-441).
The OS of white patients increased from 23 months in the era 1 to 27 months in era 2, to 36 months in the era 3 (p <0.001), representing improvements 15% and 25%, respectively; the OS of black patients increased from 27 months to 28 months to 36 months (p <0.001), representing only improvements of 4% and 22% respectively.
In patients under 65 years old at diagnosis, those most likely to be candidates for ASCT, the OS of white patients increased from 35 months in era 1 to 52 months in era 2, to 69 months in era 3 (p <0.001), representing improvements 33% and 25%, respectively; the OS of black patients increased from 36 months to 41 months to 58 months (p <0.001), representing improvements of 12% and 29% respectively.
During era 1 being younger and/or being black were both independently associated with improved OS while SES was not associated with OS. In era 2 and era 3 being younger, being white, and/or being higher SES were all independently associated with improved OS. Table 1 summarizes the results from the multivariate cox regression analysis.
Table 1- Multivariate Overall Survival Analysis Era 1 (1973-1994) Era 2 (1995-2002) Era 3 (2003-2010) Age HR1 (95% CI) p value HR1 (95% CI) p value HR1 (95% CI) p value <65 12 12 12 65-69 1.32 (1.27-1.38) < 0.001 1.48 (1.41-1.55) < 0.001 1.37 (1.31-1.45) < 0.001 70+ 1.85 (1.80-1.91) < 0.001 2.26 (2.19-2.34) < 0.001 2.56 (2.47-2.64) < 0.001 Race White 12 12 12 Black 0.95 (0.91-0.98) 0.005 1.05 (1.01-1.09) 0.008 1.04 (1.01-1.08) 0.025 SES High 12 12 12 Middle 0.98 (0.95-1.01) 0.230 1.08 (1.04-1.12) < 0.001 1.14 (1.10-1.18) < 0.001 Low 1.01 (0.98-1.04) 0.662 1.13 (1.09-1.17) < 0.001 1.22 (1.17-1.26) < 0.001 1- Hazard Ratio is adjusted for all other variables within the model 2- Used as the Reference level
Conclusions: As previously reported, the improvements in OS following the use of ASCT for MM disproportionally benefited patients who were a younger age at diagnosis and/or were white. In addition, higher SES patients benefited more than lower SES, a novel finding. Bortezomib and lenalidomide have equally benefited both black and white patients, but has worsened the outcome disparities for patients over 70 years of age at diagnosis and/or those with lower SES.

Disclosures
No relevant conflicts of interest to declare.