Background: Racial/ethnic minorities have been underrepresented in most population-based studies of AL amyloidosis published to date. This observation stands in marked contrast to multiple myeloma, a closely related disorder with a twofold higher incidence among blacks vs. whites. Given the scarcity of information about health disparities in AL amyloidosis, we aimed to characterize the clinical presentation and outcomes of this unique plasma cell disorder according to race/ethnicity.
Methods: Data on consented patients with systemic AL amyloidosis seen at the Boston University Amyloidosis Center between 1990 and 2020 were obtained from a prospectively maintained database (ClinicalTrials.gov Identifier: NCT00898235). Sociodemographic factors, hematologic and organ disease markers, along with the use of high-dose melphalan and stem cell transplantation (HDM/SCT) were stratified by self-reported race/ethnicity. Groups included non-Hispanic white (NHW), non-Hispanic black (NHB), Hispanic, and non-Hispanic other (NHO). Differences were assessed by χ2 test for categorical variables and one-way ANOVA test for continuous variables. Multivariable logistic regression was used to determine the influence of variables on HDM/SCT utilization. The effect of race/ethnicity on mortality was estimated by multivariate Cox proportional hazards regression with adjustment for relevant confounders.
Results: In a cohort of 2,416 patients, only 14% were underrepresented minorities (Figure 1A). At diagnosis, racial/ethnic minority groups were younger than NHWs by a median of 4-6 years. NHBs comprised 8% of the cohort and had higher-risk sociodemographic factors (e.g. educational attainment of high school level or less among 39% vs. 25% for NHWs; P < .001). Furthermore, there was an indication of more aggressive disease among NHBs with more patients having a difference between involved and uninvolved free light chains (dFLC) of > 180 mg/L (39% vs. 22-33%; P = .044). Hispanics comprised 4% of the cohort and presented with more advanced cardiac disease (i.e. median BNP of 1,041 pg/mL vs. 221-480 pg/mL; P = .001).
Among a subcohort of 1,668 patients with available treatment data, 33% of Hispanics and 39% of NHBs were treated with HDM/SCT as compared to 47% of NHWs (P = .071). This treatment disparity was accounted for by sociodemographic (i.e. lower educational level) and physiologic risk factors (i.e. stage III cardiac involvement), rather than race/ethnicity itself. At data cutoff in March 2020, 1,622 (67%) patients were deceased. Compared with NHWs, the median survival for NHBs was shorter by nearly one year (Figure 1B) with an age/sex-adjusted HR for death of 1.24 (95% CI 1.03-1.49; P = .020). After further adjusting for disease and treatment variables, this survival difference was eliminated altogether (HR 0.82; 95% CI 0.50-1.34; P = .427).
Conclusions: For the first time, this study shines a spotlight on racial/ethnic disparities in AL amyloidosis. Systematic underdetection, along with delayed diagnosis and referral, may explain why minority patients bear a disproportionate burden of late-stage cardiac involvement and high dFLC at the time of initial presentation. In turn, these factors contribute to underutilization of effective treatments such as HDM/SCT (particularly among Hispanics) and poorer survival (among NHBs) as observed in our study. The possibility of predisposing genetic and/or biological factors will need to be considered in future studies. Ultimately, greater awareness of AL amyloidosis within underrepresented communities, together with more widespread and accessible testing, are necessary to mitigate these health disparities.
Figure 1:(A) The distribution of race/ethnicity in a large cohort of patients with AL amyloidosis and (B) Kaplan-Meier survival curves are shown. NHW indicates non-Hispanic white; NHB, non-Hispanic black; and NHO, non-Hispanic other.
Sanchorawala:Caleum: Other: advisory board; Proclara: Other: advisory board; Abbvie: Other: advisory board; UpToDate: Patents & Royalties; Regeneron: Other: advisory board; Janssen: Research Funding; Takeda: Research Funding; Celgene: Research Funding; Prothena: Research Funding; Caelum: Research Funding; Oncopeptide: Research Funding.
Asterisk with author names denotes non-ASH members.