Primary Therapy Outcomes By Primary Cytogenetic Subtypes in a Large Cohort of Black Patients with Multiple Myeloma at a Single Center
Authors: Hiruy Semegne , Robinson Myra , Atrash Shebli , Paul Barry , Friend Reed , Varga Cindy , Ferreri Christopher J , Pineda-Roman Mauricio , Voorhees Peter M. , Bhutani Manisha 
Published: December 2024

Background: Multiple myeloma (MM) is a genetically diverse disease with varying prognosis. It occurs 2-3 times more frequently in Black individuals, who also experience a lower annual percentage improvement in survival compared to White patients. The role of cytogenetic (CG) subtypes in outcomes for Black patients remains unclear. While previous studies suggest CG differences between racial groups in MM, data on Black patients are limited. Here, we examined differences in initial treatment response and outcomes across initial therapy regimens based on CG groups.

Methods: The retrospective data from 1/2012 to 3/2022 were abstracted from the Levine Cancer Institute MM database for Black patients with MM who underwent CG testing by FISH at diagnosis. Patients received various treatments based on the prevailing standards at the time of diagnosis, categorized into major classes including Immunomodulatory drug (IMiD)-based, proteasome inhibitor (PI)-based, IMiD +PI combinations, and CD38 monoclonal antibody (daratumumab-based) combinations. We compared patient characteristics and treatment outcomes across three CG groups: standard-risk (SR) [t(11;14), t(6;14), non-standard IgH rearrangement, monosomy 13, and normal FISH]; high-risk (HR) [t(14;16), t(14;20), t(4;14), del17p, del1p, 1q gain/amp]; and exclusive trisomy (without translocations or HR CGs). Patient and disease characteristics were compared using Fisher's exact or chi-squared tests for categorical variables and Kruskal-Wallis tests for continuous variables. Time-to-event outcomes were assessed with Kaplan-Meier methods and compared between CG groups with log-rank tests. Cox proportional hazards regression was used for multivariable analysis of PFS and OS after adjusting for disease features.

Results: 467 eligible Black patients were included, with a median age of 63 years, 45% of whom were female. Among them, 111 (23.8%) showed no abnormality by FISH. Trisomy alone (without translocations or other HR CGs) was identified in 19.5%., while HR translocations and/or other HR CGs with trisomy accounted for 19.1%. HR translocations without trisomy were observed in 7.1%, SR translocations with or without trisomy in 14.6%, isolated monosomy 13 in 4.9%, and isolated HR CGs (excluding HR translocations) in 11.1%. When divided by CG groups, trisomy accounted for 19.5%, SR for 43.3%, and HR for 37.3%. Patient characteristics such as age, sex, renal failure, hypercalcemia, and lytic bone disease were similar across CG groups. Anemia was more frequent in the HR CG group (76.9%) compared to the overall cohort (69.5%). R-ISS stage did not significantly differ among CG groups.

Among 456 treated patients, 45.8% received a PI+IMiD regimen (mostly lenalidomide, bortezomib and dexamethasone) first line, and 39.9% underwent upfront autologous stem cell transplantation (ASCT). The overall response rate (ORR) to initial therapy was 91.7%, with 63.4% achieving a very good partial response or better. ORR was similar among CG groups (93.9% in HR, 91.6% in SR, and 87.6% in trisomy). Median OS was 5.8 years in HR, 7.3 years in SR, and 9.3 years in trisomy groups (p=0.01). Progression-free survival (PFS) did not differ significantly across CG groups (p=0.11). With univariable Cox regression, CG group was not associated with PFS (p=0.12). After adjusting for renal failure, hypercalcemia, ISS, therapy type, maintenance, ASCT, and response to first therapy, the association between CG group and PFS remained insignificant (p=0.13). Although significant in univariable Cox regression (p=0.01), after adjusting for age, ISS, maintenance, and ASCT, there was no significant association between CG group and OS (p=0.122).

Conclusion: To our knowledge, this is the largest single institution report on CG in Black patients with MM. Our findings underscore the impact of CG subtypes on MM outcomes in Black patients, highlighting the need for tailored therapeutic approaches based on genetic risk stratification. We plan to abstract our data for the White cohort (n=1500) to compare the prevalence of CG subtypes between Black and White patients, as well as compare the primary therapy outcomes between Black and White patients with MM after adjusting for primary CG subtype.