Muscle Mass May Presage CAR T Outcomes

TOPLINE:

Sarcopenia, a hallmark of cancer cachexia, is associated with poor outcomes in chimeric antigen receptor (CAR) T-cell therapy, which can exacerbate muscle loss through inflammatory responses. The relationship between CAR T-cell therapy, sarcopenia, and metabolism requires further investigation to improve patient outcomes.

METHODOLOGY:

• Researchers measured skeletal muscle index from clinical images in 83 patients with large B-cell lymphoma at baseline and days 30 and 90 post-therapy.
• Serum metabolomics analysis was performed in 57 patients during the first 4 weeks.
• Patients received axicabtagene ciloleucel, tisagenlecleucel, or lisocabtagene maraleucel in a standard-of-care setting at Moffitt Cancer Center between December 2017 and March 2022.
• Analysis included measurement of tissue cross-sectional areas using SliceOmatic software on abdominal CT images at mid-L3 vertebra level, with assessors blinded to imaging timing.

TAKEAWAY:

• Baseline sarcopenia was present in over half of patients and linked to shorter median overall survival compared with nonsarcopenic patients (10.5 vs 34.3 months; P = .006).
• All six nonrelapse mortality events occurred in patients with baseline sarcopenia.
• One third of patients experienced > 10% skeletal muscle loss in the first 30 days after CAR T-cell therapy, associated with higher tumor burden and neurotoxicity.
• Serum metabolomics revealed early increases in purine metabolites (weeks 1-2), followed by later increases in triglyceride levels (weeks 3-4).

IN PRACTICE:

“CAR T-cell therapy is associated with fatty acid catabolism and skeletal muscle loss is common. Patients with baseline sarcopenia have poor tolerance. Strategies focusing on diet, exercise, and/or fatty acid metabolism are warranted to attempt to improve patient outcomes,” the authors of the study wrote.

SOURCE:

This study was led by Khushali Jhaveri, MD, Moffitt Cancer Center, Tampa, Florida, and Neeraj Saini, MD, of The University of Texas MD Anderson Cancer Center, Houston. It was published in Clinical Cancer Research (AACR Journals) in April.

LIMITATIONS:

The retrospective single-center design and small sample size may have limited the power and generalizability of the findings. While precision error in measuring skeletal muscle using abdominal CT scans exists, images were assessed while blinded to their timing and significant muscle loss was defined as ≥ 10%, well beyond established precision error estimates. Analysis of muscle loss over time, particularly at day 90, was affected by bias from patient exclusions due to competing risks, as patients with progressive disease before day 90 were excluded due to lack of imaging. 

DISCLOSURES:

Saini reported receiving research funding from Panbela Therapeutics. Michael D. Jain disclosed receiving consultancy/advisory roles for Kite/Gilead, Novartis, and Myeloid Therapeutics, along with research funding from Kite/Gilead, Incyte, and Loxo@ Lilly. Additional disclosures are noted in the original article.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication.