Prognostic Value of Specific High-Risk Cytogenetic Abnormalities and Ethnicity in Outcomes after Autologous Stem Cell Transplant in Multiple Myeloma
Authors: Basher Fahmin , Sanchez Sandra , Hoffman James E. , Lekakis Lazaros J. , Pereira Denise 
Published: November 2021

Abstract
Background:
Chromosomal abnormalities in multiple myeloma (MM) patients, identified by either conventional metaphase cytogenetics or fluorescence in situ hybridization (FISH), stratify those at high risk of relapse and poorer survival after treatment. However the prognostic value of high-risk (HR) features in regard to survival after autologous hematopoietic stem cell transplantation is unclear. In addition, recent epidemiologic studies describe difference between Hispanic and non-Hispanic whites (NHW) in incidence, age at presentation, time to initial treatment, and rate of auto-HSCT within one year of diagnosis, but the presence of cytogenetic abnormalities as a prognostic factor in Hispanic patients has not yet been described.
Methods:
We conducted a retrospective analysis of 367 MM patients at the University of Miami Sylvester Comprehensive Cancer center who underwent auto-HSCT between January 2014 and December 2020. Patients were classified as HR if either conventional cytogenetics or FISH demonstrated at least one of the following: 1q+, 1p-, 17p-, 13q-, t(4;14), or t(14;16). All other patients with normal chromosomal studies or with trisomies and/or hyperdiploidy were considered standard risk (SR). Survival analysis were performed using the log-rank test, with significance at p-value &lt; 0.05.
Results:
Male patient comprised 58% of our patient population with 43% of patients of Hispanic ethnicity. Of the 367 patients who underwent auto-HSCT, 183 (50%) had at least one HR cytogenetic abnormality. Overall, HR patients exhibited inferior PFS (32.9m vs 50.6m, p=0.017) and OS (median not reached/NR for both, p=0.0086) compared to SR patients.
When evaluating outcomes with specific HR cytogenetic abnormalities, we identified cohorts that did not exhibit survival benefit, either in overall survival (OS) or progression-free survival (PFS) after transplant compared to SR patients, in particular patients with 17p-, 13q-, or 1q+ (Table 1). Patients with 1p-, t(14;16) or t(4;14) derived partial benefit from transplant in terms of PFS but not OS. Notably, patients with 1p- exhibited significantly worse OS compared to other HR patients (38.3m vs NR, p=0.007).
We next evaluated differences in outcome when stratifying across ethnicity. Of the 183 patients with HR cytogenetic abnormalities, 75 (41%) were of Hispanic ethnicity, while 58 (32%) were NHW and 46 (25%) were of African-American (AA) ethnicity. The proportion of patients with SR or each individual HR cytogenetic abnormality was mostly equivalent amongst each ethnicity with the exception of 13q- (35% of Hispanic patients, vs. 44% of NHW and 26% of AA patients). Nevertheless, we observed that Hispanic patients with either t(4;14) or 13q- had significantly worse OS and PFS than their NHW and AA counterparts, and similarly observed inferior OS in Hispanic patients with 1q+ (Table 2).
Conclusion:
In our single-center retrospective analysis of HR MM patients undergoing auto-HSCT, we have identified specific patient populations that derive some survival benefit from transplant as well as populations that did not derive any benefit. Additionally, we demonstrate that despite similar incidence of certain HR abnormalities when comparing across ethnicities, Hispanic patients with particular chromosomal abnormalities have inferior overall survival outcomes after transplant. Further investigation is warranted to identify patient-specific and treatment-related factors leading to inferior outcomes in this patient population.
Figure 1 Figure 1.

Disclosures
No relevant conflicts of interest to declare.