Background: Chimeric antigen receptor (CAR) T-cell therapy is a highly effective treatment for relapsed/refractory (R/R) hematologic malignancies. However, its efficacy and toxicity profile in patients with obesity is not well defined, with some clinical studies suggesting obesity may negatively impact outcomes while other studies report favorable outcomes. This study leverages a large real-world database to evaluate the impact of body mass index (BMI) on outcomes for patients treated with FDA-approved CAR T-cell therapies.

Methods: We conducted a retrospective cohort study using the TriNetX global federated health research network. We identified patients with various hematologic malignancies who received CAR T-cell therapy using ICD-10 and RXNORM codes. Patients were stratified into two cohorts based on BMI: normal (18.5−24.9 kg/m2) and obese (30−40 kg/m2). The cohorts were 1:1 propensity score matched for age, sex, race, and comorbidities. The primary outcome was all-cause mortality at 2 years, assessed with Hazard Ratios (HR). Secondary outcomes included cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome (ICANS), assessed with Odds Ratios (OR).

Results: A total of 2,988 patients (1,461 obese, 1,527 normal BMI) were identified. After 1:1 propensity score matching, 1,345 patients remained in each cohort. In the overall matched population, there was no statistically significant difference in 2-year mortality between the obese and normal BMI cohorts (HR 0.85; 95% CI, 0.69–1.05). Similarly, no significant differences were observed for the incidence of CRS (OR 1.02; 95% CI, 0.86–1.20) or ICANS (OR 1.02; 95% CI, 0.69–1.52).

Subgroup analyses also showed no significant association between obesity and outcomes. For patients with Diffuse Large B-Cell Lymphoma (DLBCL), there was no difference in mortality (HR 1.01; 95% CI, 0.72–1.42), CRS (OR 1.03; 95% CI, 0.72–1.48), or ICANS (OR 1.21; 95% CI, 0.51–2.86). Likewise, in patients with Multiple Myeloma (MM), mortality was not significantly different between the cohorts (HR 0.71; 95% CI, 0.38–1.32).

Conclusion: In this large, real-world analysis of patients treated with CAR T-cell therapy, obesity was not associated with a significant difference in 2-year mortality or rates of treatment-related CRS and ICANS. These findings suggest that CAR T-cell therapy is a safe and effective treatment for patients with hematologic malignancies regardless of BMI. Our results do not support the existence of an “obesity paradox” in this setting but, importantly, alleviate concerns that obesity may adversely impact CAR T-cell therapy outcomes. Therefore, eligible patients should be considered for this potentially curative therapy without regard to their BMI.

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2025
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