Cancer Cachexia and Weight Loss Before CAR T-cell Therapy for Lymphoma Are Independently Associated with Poor Outcomes

Chimeric antigen receptor (CAR) T-cell therapy has transformed the care of lymphoma, yet many patients relapse. Several prognostic markers have been associated with CAR T-cell outcomes, such as tumor burden, response to bridging chemotherapy, and laboratory parameters at the time of lymphodepletion or infusion. The effect of cancer cachexia and weight loss before CAR T cells on toxicity and outcomes is not well understood. Here, we present a retrospective single-institution cohort study of 259 patients with lymphoma treated with CAR T cells between 2017 and 2023. We observed that patients with >5% decrease in their body mass index in the 3 months preceding CAR T-cell treatment (weight loss group; all meeting one of the commonly accepted definitions of cancer cachexia) had higher disease burden and inflammatory parameters (C-reactive protein, ferritin, interleukin-6, and tumor necrosis factor α) at the time of lymphodepletion and CAR T-cell infusion. Patients with weight loss experienced higher rates of grade 3+ neurotoxicity and early hematotoxicity, but those effects were not seen upon multivariable adjustment. However, in both univariate and multivariable analysis, patients with weight loss had worse response rates, overall survival, and event-free survival, indicating that weight loss is an independent poor prognostic factor. Our data suggest that weight loss in the 3 months preceding CAR T-cell therapy represents a worrisome "alarm signal" and a potentially modifiable factor, alongside tumor burden and inflammation, and warrants further investigation in patients treated with CAR T-cell therapy.