ASH Abstracts Reveal Disparate CAR T-Cell Therapy Access and Outcomes in MM, DLBCL

Access to and outcomes of chimeric antigen receptor (CAR) T-cell therapies may differ by characteristics such as race, ethnicity, gender, and geographic location among patients with cancer, according to data from abstracts presented at the 64th American Society of Hematology Annual Meeting and Exposition in December.^1,2

These individualized treatments represent an innovative form of immunotherapy that can induce durable disease response, but prior research has suggested that these breakthrough therapies may not be reaching all patients equally. One abstract presented at the meeting detailed a study examining predictors of CAR T-cell therapy receipt among Medicare patients with relapsed/refractory diffuse large B-cell lymphoma (DLBCL) who had at least 2 prior lines of therapy.¹

The investigators linked claims data to individual characteristics and county-level measures of socioeconomic disadvantage. Of 15,472 patients with DLBCL, they focused on the 266 patients who had received rituximab (Rituxan) plus chemotherapy as their first line of treatment and then received either CAR T-cell therapy (n=104) or a comparator therapy (n=162) as a third or later line of therapy. These comparator therapies included stem cell transplant, polatuzumab-based therapy, and salvage combinations of rituximab and chemotherapy.

Unadjusted analysis showed that patients 76 years and older were less likely to receive CAR T-cell therapy than those aged 66 to 75 years, but the difference was not statistically significant (odds ratio [OR], 0.501; P = .06).

After excluding patients who were evaluated for clinical trial participation, leaving 65 patients who received CAR T-cell therapy and 144 who received a comparator, multivariate adjusted analysis showed that CAR T-cell therapy recipients were less likely to be women (OR, 0.463; P = .04), have a Charlson Comorbidity Index score of at least 3 (OR, 0.451; P = .04), or be residents of the American South (OR, 0.284; P = .02). However, no association was observed between CAR T receipt and Area Deprivation Index.

“Despite the small sample size of this study, the findings suggest that access to CAR T-cell therapy should be particularly improved in female patients and patients living in the South, possibly due to geographical limitations of CAR T centers and a high population of socioeconomically disadvantaged racial minorities,” the authors wrote.

Even when patients do receive CAR T-cell therapy, however, disparities can persist. A second abstract detailed how investigators harnessed data from the US MM Cellular Therapy Consortium of 215 patients with relapsed/refractory multiple myeloma (MM) who received idecabtagene vicleucel (ide-cel), a CAR T-cell therapy approved by the FDA in March 2021.² The investigators noted that, although the KarMMa clinical trial (NCT03361748) showed impressive efficacy data for ide-cel, racial and ethnic minority groups were underrepresented in its participants. As such, they aimed to shed light on the safety and efficacy of ide-cel in diverse, real-world patient populations.

The 215 patients in this analysis were treated at 11 institutions and had a median age at ide-cel infusion of 64 years (range, 36-83 years). They had received a median of 6 prior lines of therapy before receiving ide-cel (range, 3-19). More than 3 in 4 (76%) would have been excluded from the KarMMa trial.

According to self-reported identification, 70% (n=150) of patients were non-Hispanic White, 17% (n=36) were non-Hispanic Black, 10% (n=21) were Hispanic, and 3% (n = 8) were Asian, Pacific Islander, American Indian, or Alaskan Native. The latter group was omitted from the analysis due to the small sample size.

Among the 215 participants, the best overall response rate was 84%, and 34% of patients achieved at least a complete response (CR). Of these 83 patients who achieved a CR or better, 66% were minimal residual disease negative.

Analysis by race and ethnicity showed that Black patients were more likely to experience several negative outcomes compared with White and Hispanic patients. They were more likely to:

• develop any grade cytokine release syndrome: 97% vs 84% and 76%; P = .05
• have a longer hospital stay: median, 12.5 days vs 9 days and 8 days; P = .01
• experience severe prolonged cytopenia: 87% vs 72% and 56%; P = .07

Although overall survival was similar across the racial and ethnic groups, Hispanic and Black patients combined had shorter progression-free survival compared with White patients (median, 5.9 vs 9.0 months; P = .08), which appeared to be driven by a worse overall response rate among Hispanic patients.

The authors of the abstract concluded that their data showed racial and ethnic differences in safety and progression-free survival among patients receiving ide-cel for relapsed/refractory MM.

“As a greater volume of patients are treated with CAR T therapy and follow-up time matures, we will have increased power to further investigate racial and ethnic differences in patient and clinical characteristics and clinical outcomes,” they wrote.

References

1. Saunders A, Inguva S, Keating SJ, Chirikov V. Examination of disparities in access to chimeric antigen receptor (CAR) T cell therapies in Medicare patients (pts) with relapsed or refractory (R/R) diffuse large B-cell lymphoma (DLBCL) who had failed at least 2 prior lines of therapy (LOT). Presented at: 64th American Society of Hematology Annual Meeting and Exposition December 10-13, 2022; New Orleans, LA. Abstract 4906. Accessed December 19, 2022. https://ash.confex.com/ash/2022/webprogram/Paper160313.html
2. Peres LC, Oswald LB, Dillard C, et al. Racial and ethnic differences in clinical outcomes among multiple myeloma patients treated with CAR T therapy. Presented at: 64th American Society of Hematology Annual Meeting and Exposition; December 10-13, 2022; New Orleans, LA. Abstract 252. Accessed December 16, 2022. https://ash.confex.com/ash/2022/webprogram/Paper158478.html