To the Editor,
Ciltacabtagene autoleucel (cilta-cel) and idecabtagene vicleucel (ide-cel) are B- cell maturation antigen-directed chimeric antigen (BCMA) receptor T-cell (CAR T) therapies approved for relapsed/refractory multiple myeloma (RRMM) and increasingly used earlier in the treatment course [ 1 – 4 ]. However, racial minority populations remain underrepresented in CAR T trials. For example, Black patients accounted for only 2.9% of participants in CARTITUDE-4 and 7% in KarMMA-3 [ 3 , 4 ]. This underrepresentation may contribute to disparities in both access and outcomes. Although racial differences in CAR T outcomes have been studied, most available data pertain to non-Hodgkin lymphoma and B-cell acute lymphoblastic leukemia [ 5 – 7 ], with limited evidence specific to MM [ 8 , 9 ].
We conducted a retrospective analysis of consecutive patients with RRMM who received commercial cilta-cel or ide-cel between May 2022 and April 2024 across five academic centers: Levine Cancer Institute, Ohio State University, University of Kansas Cancer Center, University of Iowa, and Medical University of South Carolina. Institutional review boards at each site approved the study with a waiver of informed consent. Demographic and clinical data were extracted from electronic medical records. Management of cytokine release syndrome (CRS), immune-effector cell-associated neurotoxicity syndrome (ICANS), infections, and supportive care followed institutional protocols. Race and ethnicity were self-reported and categorized as White patients (WP) versus minority patients (MP), which included African American and/or Black, Asian, Hispanic/Latino, and other. Due to limited sample sizes, minority groups were combined for analysis. Outcomes, including CRS, ICANS, cytopenia, response rates, progression-free survival (PFS), and overall survival (OS), were compared between groups. Treatment response was assessed by treating physicians per standard criteria [ 10 ] at 1-, 3-, and 6-months post-CAR T infusion. Descriptive statistics and group comparisons were performed using Fisher’s exact and Wilcoxon rank-sum tests. Kaplan-Meier curves and log-rank tests were used for survival analysis.
Of the 223 patients treated with cilta-cel or ide-cel, 177 (79%) were WP and 46 (21%) were MP. Among the 46 MP, 39 were Black or African American, 2 Asian, 2 Hispanic or Latino, and 3 identified as other. Baseline comparisons (Table 1 ) showed that MP were younger at infusion (median age 61.5 vs. 66 years; p = 0.012), less often male (43% vs. 59%; p = 0.054), and more likely to have ECOG ≥ 2 (18.8% vs. 7.5%; p = 0.0795) and renal dysfunction (22% vs. 8.5%; p = 0.011). Baseline ferritin levels were higher in MP compared to WP (median 477 vs 201 ng/mL; p = 0.007). Baseline CRP levels were similar between groups (median 0.8 vs 0.7 mg/dL; p > 0.9).
Table 1
Baseline clinical and disease characteristics.
| Characteristic | Minority, N = 46 | White, N = 177 | p -value |
| Age (median, years) | 61.5 (41.0–83.0) | 66.0 (34.0–84.0) | 0.012 |
| Male | 20 (43%) | 105 (59%) | 0.054 |
| ECOG | 0.033 | ||
| 0 | 2 (4.4%) | 22 (14%) | |
| 1 | 35 (78%) | 125 (79%) | |
| 2 | 7 (16%) | 12 (7.5%) | |
| 3 | 1 (2.2%) | 0 (0%) | |
| Heavy Isotype | 0.8 | ||
| IgA | 7 (15%) | 35 (20%) | |
| IgG | 29 (63%) | 104 (59%) | |
| Light chain disease | 10 (22%) | 37 (21%) | |
| Light Chain | 0.6 | ||
| Kappa | 26 (57%) | 109 (62%) | |
| Lambda | 20 (43%) | 67 (38%) | |
| R-ISS stage | 0.082 | ||
| 1 | 5 (16%) | 34 (24%) | |
| 2 | 12 (39%) | 70 (50%) | |
| 3 | 14 (45%) | 35 (25%) | |
| Unknown | 15 | 38 | |
| High-risk cytogenetics | |||
| Deletion 17p | 7 (15%) | 38 (21%) | 0.3 |
| t(4;14) | 4 (8.7%) | 18 (10%) | >0.9 |
| t(14;16) | 2 (4.3%) | 8 (4.5%) | >0.9 |
| Plasma cell leukemia | 1 (2.2%) | 3 (1.7%) | >0.9 |
| Extra medullary disease | 16 (35%) | 67 (38%) | 0.7 |
| CrCl <45 | 10 (22%) | 15 (8.5%) | 0.011 |
| Prior transplant | 37 (80%) | 148 (84%) | 0.6 |
| Prior lines of therapy | 5.0 (0.0–12.0) | 6.0 (1.0–13.0) | 0.5 |
| Refractory Status | |||
| Bortezomib refractory | 28 (61%) | 95 (54%) | 0.6 |
| Carfilzomib refractory | 33 (72%) | 125 (71%) | 0.4 |
| Lenalidomide refractory | 36 (78%) | 137 (77%) | 0.5 |
| Pomalidomide refractory | 38 (83%) | 131 (74%) | 0.5 |
| Anti-CD38 refractory | 42 (91%) | 163 (92.1%) | 0.6 |
| Previous anti-BCMA exposed | 7 (15%) | 22 (12%) | 0.6 |
| Baseline Ferritin (ng/mL) | 477 (IQR: 143–1012) | 201 (IQR: 74–518) | 0.007 |
| Baseline CRP (ng/dL) | 0.8 (IQR: 0.0–3.2) | 0.7 (IQR: 0.0–3.5) | >0.9 |
| Product | 0.7 | ||
| cilta-cel | 16 (35%) | 57 (32%) | |
| ide-cel | 30 (65%) | 120 (68%) |
Among the cohort, 41% of MP and 24% of WP would have been ineligible for KarMMa and CARTITUDE trials ( p = 0.017). Reasons for ineligibility included EF < 45%, CrCl <45 ml/min, plasma cell leukemia, concomitant AL amyloidosis, and prior anti-BCMA therapy (Supplementary Table 1 ).
Among MP, 35% received cilta-cel and 65% ide-cel, compared to 32% and 68%, respectively, among WP. No significant differences in overall response rate (ORR) or depth of response were observed at different time points (Fig. 1 ). At 6 months, the ORR was 84% in MP vs. 71% in WP ( p = 0.4), with a stringent complete response observed in 17% vs. 25%, complete response in 25% vs. 17%, very good partial response in 25% vs. 24%, partial response in 17% vs. 4.7%, and progressive disease in 17% vs. 26%, respectively.
Any grade CRS occurred in 87% of MP vs. 80% of WP ( p = 0.30), and ICANS in 30% vs. 18% ( p = 0.065) (Supplementary Table 2 ). ICANS ≥grade 3 was 8.7% in MP vs 1.7% in WP. No clear association was observed between elevated ALC ( > 3 × 10⁹/L) and ICANS or neurotoxicity (non-ICANS) in either racial group (Supplementary Tables 3 , 4 ). Baseline ferritin was significantly higher in WP who developed ICANS ( p = 0.008), while CRP showed no significant difference across ICANS status. ICANS was strongly associated with neurotoxicity in both MP and WP (Supplementary Table 4 ). Detailed qualitative neurotoxicity data were not uniformly available across centers; however, overall neurotoxicity rates were comparable (17% in MP vs 8.5% in WP; p = 0.1).
Hematologic toxicities were generally comparable between groups (Fig. 1 ), except for neutropenia on day 60, where median ANC was lower in MP (1.46 vs. 2.50 k/µL; p = 0.003). Grade 4 neutropenia was more frequent in MP (41% vs. 21%; p = 0.012), while grade 3/4 thrombocytopenia was higher but not statistically significant (61% vs. 48%; p = 0.15) (Supplementary Table 5 ). Baseline ANC values prior to lymphodepletion chemotherapy were similar between MP and WP (median, 2.5 vs 2.2 × 10⁹/L; p = 0.2). Infections of any grade post CAR T infusion were reported in 30% of MP and 21% WP ( p = 0.20), and neutropenic fever rates were identical (22% in both groups; p > 0.9). One grade 5 infection occurred in MP (2.2%) and one in WP (0.6%). Bacterial infections were numerically more frequent in WP (12.4% vs 6.5%), while viral infections were slightly more common in MP (13% vs 9.6%), though none of these differences were statistically significant (Supplementary Table 6 ). Stem cell boosts were required in 17% of MP vs. 10% of WP.
Median follow-up was 27.8 months overall, similar between groups. Median PFS was 16.1 months in MP vs. 14.1 months in WP; OS was 26.4 vs. 27.9 months, respectively. No significant differences were observed in PFS ( p = 0.81; HR 1.07) or OS ( p = 0.42; HR 0.78) (Fig. 1 ). Median PFS and OS were longer with cilta-cel than ide-cel in both WP and MP, with significant PFS benefit in WP ( p = 0.005) and favorable trends in other groups (Supplementary Table 7 ).
Conducted across multiple academic centers serving racially diverse populations, our study included 21% MP, with African American individuals comprising the majority (39 of the 46). Two other real-world studies of CAR T-cell therapy in RRMM reported Black patient representation at 17% and 15%, respectively [ 8 , 11 ]. While the proportion of African American and/or Black patients exceeds that reported in pivotol trials for ide-cel and cilta-cel, the absolute number remains modest given the 2- to 3-fold higher incidence of MM in African American populations. MP were also younger at infusion, which may reflect referral or access biases rather than true age distribution.
Although Duffy antigen status was unavailable in our dataset, baseline ANC prior to lymphodepletion was similar between WP and MP, suggesting that initial counts do not account for the higher incidence of grade 4 neutropenia in MP. Importantly, these higher neutropenia rates did not translate into more infection-related complications. The Duffy-null genotype, common among individuals of African ancestry, may contribute to this difference; a recent study showed that Duffy-null and non-null patients had similar baseline ANC but significantly lower counts in the Duffy-null group by day 60 post-CAR T [ 12 ].
A significantly higher proportion of MP in our cohort would have been excluded from landmark CAR T trials due to eligibility criteria, particularly renal dysfunction. Similarly, a previous real-world study found that 75% of patients were ineligible for the KarMMa trial [ 8 ]. This highlights how current trial eligibility criteria, while intended for safety, may inadvertently exclude a significant proportion of MP with comorbidities and limit the applicability of trial results to real-world settings. More flexible trial designs are needed to broaden eligibility and ensure equitable access to emerging therapies.
Unlike prior studies suggesting racial differences in inflammatory markers, response rates, and CRS incidence [ 8 , 9 ], we observed no differences in CRS, ICANS, or ORR between WP and MP. PFS and OS were also comparable, aligning with other real-world studies showing similar survival outcomes across racial groups [ 5 – 8 ]. Emerging evidence shows similar patterns in autologous stem cell transplantation, where Black patients may achieve survival outcomes equal to or better than WP after adjusting for sociodemographic factors [ 13 , 14 ]. These findings underscore the importance of equitable access to care. Increasing cellular therapy utilization among racial minority populations will require multifaceted efforts, including improving referral pathways, expanding access to CAR T centers, addressing insurance and financial barriers, and enhancing provider awareness of disparities.
A key limitation of this study is that it includes only patients with RRMM referred to academic centers who received CAR T therapy, without accounting for those who may have faced physical, socioeconomic, or systemic barriers to access. CAR T therapy remains largely confined to specialized centers, and access is influenced by geography, healthcare infrastructure, referral patterns, insurance coverage, and stringent eligibility criteria [ 15 ]. As with other observational studies, our analysis is also subject to missing data, as collection was site-dependent and aligned with routine clinical practice. Finally, most patients had heavily pretreated RRMM, so survival outcomes may not be generalizable to those treated earlier in their disease course, which is particularly relevant as CAR T therapy is increasingly used in earlier lines of treatment.
In conclusion, these real-world findings support the safety and efficacy of CAR T-cell therapy across racial groups among patients who are able to access treatment. Future prospective trials should prioritize greater representation of racial and ethnic minority groups and broaden the eligibility criteria to more effectively inform treatment strategies and reduce disparities in access and outcomes.
Supplementary information
Supplemental File
Acknowledgements
The authors gratefully acknowledge the support of the U.S. Myeloma Innovations and Research Collaborative (USMIRC) for its contributions to this work, including assistance with study design, critical review of the manuscript, and administrative coordination.
Author contributions
MB contributed to study design, data collection and interpretation, provided patient cases, and drafted and edited the manuscript. SA contributed to concept development, data collection and interpretation, provided patient cases, performed statistical analysis, provided figures and tables, and assisted with manuscript editing. A-OA contributed to concept development, provided patient cases, and assisted with manuscript editing. AH, AV, AN, ES, HS, DC, CS, KMG, KG, MUM, ZM, JPM, PV, AMK, and NA contributed to data collection and interpretation and provided patient cases. All authors reviewed, revised, and approved the final manuscript.
Data availability
The datasets generated during and/or analyzed during the current study are not publicly available due to HIPPA but are available from the corresponding author on reasonable request.
Competing interests
MB: Consulting or Advisory Role: Caribou Biosciences; Research Funding: Janssen (Inst), Amgen (Inst), Bristol Myers Squibb/ Celgene (Inst), Takeda (Inst), Abbvie (Inst), Caribou Biosciences (Inst), and The Binding Site (Inst). KMG: Consulting or Advisory Role: Janssen, Sanofi; Research Funding: Janssen (Inst), Abbvie (Inst), Incyte (Inst), Nexcella (Inst) MUM: Research Funding: Iovance Biotherapeutics (Inst). ZM: Leadership: Hematology Oncology Pharmacists Association; Honoraria: Bristol Myers Squibb Foundation, Kite/Gilead, Genentech, Pfizer, and Sanofi. JPM: Honoraria: Kite, a Gilead company, AlloVir, Nektar, Sana Biotechnology, Bristol Myers Squibb/Sanofi, Novartis, crispr therapeutics, CARGO Therapeutics, Autolus, Legend Biotech; Consulting or Advisory Role: Kite, a Gilead company, Juno Therapeutics, Allovir, Magenta Therapeutics, EcoR1 Capital, crispr therapeutics, Fosun Kite Biotechnology Co, Ltd, Sanofi US Services, Inc, Novartis, Nektar, Sana. Biotechnology, Inc; Speakers’ Bureau: Kite/Gilead; Research Funding: Novartis (Inst), Fresenius Biotech (Inst), Astellas Pharma (Inst), Bellicum Pharmaceuticals (Inst), Novartis (Inst), Gamida Cell (Inst), Pluristem Therapeutics (Inst), Kite, a Gilead company (Inst), AlloVir (Inst). PV: Consultancy or Advisory Role: AbbVie, AstraZeneca, BMS, Karyopharm, Lava Therapeutics, Sanofi, Regeneron, Janssen, GSK; Research Funding: AbbVie, GSK, Janssen, Regeneron. A-OA: Research Funding: Celgene (Inst), Seagen (Inst), AbbVie (Inst), Bristol Myers Squibb/Medarex (Inst), Sanofi (Inst), GlaxoSmithKline (Inst). Patents, Royalties, Other Intellectual Property: PSA vaccine patent. NA: Consulting or Advisory Role: Kite/Gilead, BMS, Legend Biotech, Invivyd; Research Funding: Kite/Gilead (Inst). SA: Leadership ACCRU; Consulting or Advisory Role: Pfizer, Sanofi: Research Funding: GlaxoSmithKline, Amgen, Karyopharm Therapeutics, Janssen Oncology (Inst), Celgene/Bristol Myers Squibb (Inst); Honoraria: Janssen, GSK, Sanofi. AH, AV, AN, ES, HS, DC, CS, KG, and AMK: These authors declare no competing financial interests.
Ethics approval and consent to participate
The study protocol (DSP00000618) was approved by the Institutional Review Board (IRB) at each participating center. All methods were performed in accordance with the relevant guidelines and regulations. A waiver of informed consent was granted by the respective IRBs.
Footnotes
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Supplementary information
The online version contains supplementary material available at 10.1038/s41408-025-01419-1.
References
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Associated Data
Supplementary Materials
Supplemental File
Data Availability Statement
The datasets generated during and/or analyzed during the current study are not publicly available due to HIPPA but are available from the corresponding author on reasonable request.