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Sarcopenia and Skeletal Muscle Loss after CAR T-cell Therapy in Diffuse Large B-cell Lymphoma
Khushali Jhaveri1, Ram Thapa1, Dalia Ercan1
1Moffitt Cancer Center, Tampa, Florida.
Summary
Sarcopenia, or muscle loss, is common after CAR T-cell therapy and linked to poor survival. Early detection and interventions may improve outcomes for cancer patients undergoing this treatment.
Area of Science:
- Oncology
- Metabolism
- Immunotherapy
Background:
- Sarcopenia is a key feature of cancer cachexia.
- Chimeric antigen receptor (CAR) T-cell therapy can induce an inflammatory state, potentially worsening sarcopenia.
- The interplay between CAR T-cell therapy, sarcopenia, and metabolic changes is not well understood.
Purpose of the Study:
- To investigate the prevalence of sarcopenia in patients with large B-cell lymphoma undergoing CAR T-cell therapy.
- To examine the relationship between baseline sarcopenia, skeletal muscle loss post-therapy, and patient survival.
- To explore metabolic alterations associated with CAR T-cell therapy and their correlation with muscle mass changes.
Main Methods:
- Skeletal muscle index (SMI) was measured from clinical images in 83 large B-cell lymphoma patients at baseline and at 30 and 90 days post-therapy.
- Serum metabolomics analysis was conducted on 57 patients within the first 4 weeks of therapy.
- Statistical analyses were performed to correlate sarcopenia, muscle loss, metabolic profiles, and clinical outcomes, including overall survival (OS) and non-relapse mortality (NRM).
Main Results:
- Over half of patients presented with baseline sarcopenia, which was significantly associated with shorter median OS (10.5 vs. 34.3 months, P=0.006) and increased NRM.
- Approximately one-third of patients experienced >10% skeletal muscle loss within 30 days post-CAR T-cell therapy, associated with higher tumor burden and neurotoxicity.
- Metabolomic analysis revealed an early increase in purine metabolites (weeks 1-2) followed by elevated triglyceride levels (weeks 3-4), with adipic acid showing the highest fold-increase.
Conclusions:
- Skeletal muscle loss is a frequent complication of CAR T-cell therapy, linked to fatty acid catabolism.
- Baseline sarcopenia predicts poor tolerance and reduced survival in patients undergoing CAR T-cell therapy.
- Future research focusing on dietary and exercise interventions is warranted to potentially enhance CAR T-cell therapy outcomes.
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