Compared with non-Hispanic white patients, non-Hispanic Black patients with relapsed or refractory multiple myeloma (R/R MM) had a higher rate of toxicities when treated with the chimeric antigen receptor (CAR) T-cell therapy idecabtagene vicleucel (ide-cel). This is according to the first ever study to examine clinical outcomes among patients of different racial and ethnic backgrounds with R/R MM who were treated with standard-of-care ide-cel. However, the analysis also showed no racial and ethnic differences in progression-free survival (PFS) and overall survival (OS) among the patients with MM. The study was published in Blood Advances.1
“[We found that there] were no racial and ethnic differences in survival, and this indicates that all patients with R/R MM, regardless of race and ethnicity, may have similar survival benefits after ide-cel in the standard-of-care setting,” said study author Lauren Peres, PhD, MPH, of Moffitt Cancer Center in Tampa, Florida.
In 2021, ide-cel became the first U.S. Food and Drug Administration-approved CAR T-cell therapy for patients with R/R MM after four or more lines of therapy. Dr. Peres and her co-authors sought to investigate racial and ethnic differences in CAR T-cell therapy outcomes in a standard-of-care setting because non-Hispanic Black and Hispanic patients are underrepresented in MM clinical trials, even though Black patients are twice as likely to be diagnosed with MM compared to white patients. Racial and ethnic disparities are particularly prevalent in MM, including that non-Hispanic Black individuals are more than twice as likely to be diagnosed with MM compared to non-Hispanic white individuals.2 Therefore, it is important to understand the impact of these disparities on outcomes among these patients.
The team pooled data from 207 patients across 11 institutions that participate in the U.S. Multiple Myeloma Immunotherapy Consortium, including 22 (11%) Hispanic, 36 (17%) non-Hispanic Black, and 149 (72%) non-Hispanic white patients.
The researchers found ethnic and racial differences in the development of toxicities and adverse events among patients with R/R MM. Non-Hispanic Black patients were more likely to develop any-grade cytokine release syndrome (CRS) compared with Hispanic and non-Hispanic white patients (97% vs. 77% and 85%, respectively; p=0.04). The differences in the any-grade CRS incidence could be explained by an elevated pro-inflammatory state before ide-cel infusion in non-Hispanic Black patients, the authors wrote in their discussion. According to the authors, prior studies have shown that patients with a baseline pro-inflammatory response are more at risk of CRS development. This finding could also be because of differences in disease burden by race and ethnicity, the authors noted, although they did not see any racial or ethnic differences in clinical marrow burden.
There were no differences in the frequencies of grade 3 or higher severe CRS or any grade or severe immune effector cell-associated neurotoxicity syndrome, nor in the use of steroids or tocilizumab. There was a higher prevalence of anakinra use among Hispanic patients compared to non-Hispanic Black and white patients (14% vs. 0% and 5%, respectively; p=0.06). Non-Hispanic Black patients also had a longer median hospital stay compared to white and Hispanic patients (13.5 vs. 9.0 and 8.0 days, respectively; p=0.006), but there were no differences in ICU admissions among the three groups.
The median follow-up for the study was 9.3 months. The best ORR was lower among Hispanic patients (59%) compared to Black (86%) and white (86%) patients (p=0.01). There was no statistical difference in PFS or OS by race or ethnicity (p=0.49 and p=0.99, respectively). After adjusting for clinically relevant co-variates, race and ethnicity were not associated with PFS or OS. The median OS was not reached on study; the median PFS was 4.2 months for Hispanic, 6.5 months for non-Hispanic Black, and 8.5 months for white patients.
“As follow-up time matures, we plan to investigate whether there are racial and ethnic differences in longer-term clinical outcomes in this population. We are also leveraging data from the U.S. Multiple Myeloma Immunotherapy Consortium to study patients treated with the second approved CAR T-cell therapy for patients with R/R MM, ciltacabtagene autoleucel. We plan to investigate racial and ethnic differences in clinical outcomes among this cohort as well,” Dr. Peres said.
“It is important to note that our findings only reflect patients who had access to ide-cel,” she added. “Our study is not able to address racial and ethnic differences in access to CAR T-cell therapy, which is a known contributor to disparities and needs further investigation in other studies.”
Other limitations cited by the researchers include the small sample size, short follow-up period, the lack of less common racial and ethnic groups, including ethnic subgroups, and the retrospective nature of the study, which cannot account for potential differences in how toxicities were managed among the various institutions.
Any conflicts of interest declared by the authors can be found in the original article.
References
- Peres LC, Oswald, L, Dillard CM, et al. Racial and ethnic differences in clinical outcomes among multiple myeloma patients treated with CAR T-cell therapy [published online ahead of print, 2023 Oct 16]. Blood Adv. doi: 10.1182/bloodadvances.2023010894.
- Benjamin M, Reddy S, Brawley, OW. Myeloma and race: a review of the literature. Cancer Metastasis Rev. 2003;22(1):87-93.
