Overweight Patients with Multiple Myeloma Experience Worse Outcomes with CAR T-Cell Therapy, Study Finds
New York, NY – A new study published in blood ICT reveals a surprising “U-shaped association” between body mass index (BMI) and outcomes for patients with multiple myeloma (MM) undergoing CAR T-cell therapy. Researchers found that patients classified as overweight experienced considerably worse progression-free survival (PFS) and overall survival (OS) compared to both normal-weight and obese individuals.
The single-center, observational study analyzed data showing a 12-month PFS rate of 28.8% for overweight patients, compared to 51.9% in normal-weight patients and 62.6% in obese patients (P < .001). Similarly, 12-month OS rates were 61.4% for the overweight group, versus 82.9% and 84.2% for normal-weight and obese patients, respectively (P = .006). Complete response rates also followed this pattern: 36.4% in overweight patients, compared to 42.9% and 56.1% in the other two groups (P = .185).
Univariate Cox regression analysis demonstrated that overweight status was associated with 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 to those with normal weight or obesity. This association remained important even after adjusting for other factors, with overweight status independently linked to worse 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).
The researchers, led by Choa et al., hypothesized that normal-weight patients may have more favorable tumor biology, while obesity could paradoxically enhance immunotherapy sensitivity, a phenomenon observed in other cancers. They propose that the “intermediary overweight state may represent a relatively immunometabolically adverse phenotype without the compensatory benefits seen at either end of the BMI spectrum.” They’ve termed this pattern an “immunometabolic valley,” with the overweight group positioned at its most disadvantageous point.
“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.
Acknowledging the study’s limitations – including potential selection bias and the inherent crudeness of BMI as a measure of health – the authors emphasize the need for future research incorporating comprehensive body composition analysis. They call for further mechanistic investigations to identify potential therapeutic targets and optimize treatment strategies for MM patients based on their metabolic profiles.
“Further validation and mechanistic research are essential to elucidate the underlying biological processes,” the authors concluded. “This [future] research could uncover novel therapeutic targets or modifiable factors to be leveraged to improve CAR T-cell therapy outcomes in MM.”
Reference: 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.
