BMI in CAR T: Overweight Status Predicts Worse MM Outcomes

TargetedOncology^® first published this article. This version has been lightly edited.

A retrospective analysis of anti–B-cell maturation antigen (BCMA) chimeric antigen receptor T-cell (CAR T) therapy outcomes in patients with multiple myeloma (MM) stratified by body mass index (BMI) has revealed poorer outcomes among patients who were overweight compared with those with normal weight and obesity.¹

This finding highlights the prognostic significance of host biologic determinants such as body mass index (BMI), warranting further investigation into how metabolic pathways and processes may shape CAR T therapeutic efficacy.

“These data support a U-shaped relationship between BMI and CAR T-cell outcomes in MM, which should motivate mechanistic studies to identify modifiable biologic factors,” wrote the authors in Blood Immunology & Cellular Therapy.

Patient Characteristics

The study examined a retrospective cohort of 134 patients with MM who received anti-BCMA CAR T-cell therapy at Massachusetts General Hospital between 2016 and 2023. Of the 134 patients, 51.5% received idecabtagene vicleucel (ide-cel; Abecma; Bristol Myers Squibb), 23.9% received ciltacabtagene autoleucel (cilta-cel; Carvykti; Johnson & Johnson), and 24.6% received an investigational therapy.

The median BMI of the cohort was 26.7 kg/m² (range, 17.9–55.2). Patients were classified into 3 main weight categories based on BMI: normal (< 25 kg/m²), overweight (25–29.9 kg/m²), and obese (≥30.0 kg/m²). Patients with normal weight, overweight, and obesity comprised 36.6%, 32.8%, and 30.6% of the whole cohort, respectively.

Key Findings: A U-Shaped Association

Stratifying results by BMI, patients classified as overweight had a numerically worse 12-month progression-free survival (PFS) compared with those with normal weight and those with obesity (28.8% vs 51.9% vs 62.6%, respectively; P < .001). A similar pattern was observed for 12-month overall survival (OS; 61.4% vs 82.9% vs 84.2%; P = .006) and complete response rate (36.4% vs 42.9% vs 56.1%; P = .185) in the overweight, normal weight, and obese groups, respectively.

On univariate Cox regression, results showed associations between BMI and survival in which patients with overweight status had a significantly higher rate of disease progression (HR, 2.35; 95% CI, 1.5-3.67; P < .001) and death (HR, 2.38; 95% CI, 1.32-4.28; P = .004) compared with those with normal weight and obesity. Upon adjusting for covariates, overweight status remained independently associated with PFS (HR, 1.69; 95% CI, 1.03-2.77; P = .038) and OS (HR, 2.33; 95% CI, 1.08-5.03; P = .031) in the multivariate-adjusted models.

These findings align with the authors’ original hypothesis that overweight status lacks the protective benefits observed in patients of normal weight or obese status, which may partially explain the worse outcomes observed in the overweight group.

“We hypothesized that normal-weight patients have more favorable tumor biology, whereas obesity may paradoxically confer enhanced immunotherapy sensitivity and CAR T-cell therapy efficacy, as seen in other cancers,” the authors wrote. “Thus, the intermediary overweight state may represent a relatively immunometabolically adverse phenotype without the compensatory benefits seen at either end of the BMI spectrum.”

The authors term this pattern an “immunometabolic valley,” positioning the overweight group at the valley’s “lowest,” most disadvantageous point.

Future Directions

As a single-center observational study, key limitations of the study noted by the authors include selection bias and the complex nature of BMI. BMI in itself is a crude surrogate, conflating adiposity and lean mass, which may not be wholly reflective of an individual’s metabolic health.² To address these shortcomings, the authors highlight the value of integrating comprehensive body composition analysis into future studies to more accurately capture the nuances overlooked in a BMI measure.

Overall, the authors call for future mechanistic investigations that could guide optimization of these treatment strategies for different groups of patients with MM.

“Further validation and mechanistic research are essential to elucidate the underlying biological processes,” wrote the authors about next steps. “This [future] research could uncover novel therapeutic targets or modifiable factors to be leveraged to improve CAR T-cell therapy outcomes in MM.”

References

1. Choa R, Miller K, Joshi A, et al. Impact of body mass index on anti-BCMA chimeric antigen receptor T-cell therapy outcomes in multiple myeloma. Blood ICT. 2025;1(3):100015. doi:10.1016/j.bict.2025.100015

2. Wu Y, Li D, Vermund SH. Advantages and limitations of the body mass index (BMI) to assess adult obesity. Int J Environ Res Public Health. 2024;21(6):757. doi:10.3390/ijerph21060757