CAR-T Meeting 2026 | The association of physical performance plus sarcopenia with outcomes in CAR-T recipients

Frailty in cancer patients is a rapidly evolving topic in hemato-oncology, driven by the need to personalize care for an aging population and to improve treatment tolerance. And real-world data suggests that chronological age alone poorly reflects outcomes and physiologic reserve in CAR T-cell recipients. So the most common use measure guiding treatment decisions is the ECOG performance status, and while ECOG is fast and practical, it is inherently subjective and rater-dependent. 

So to address this gap, we implemented a simple two-step physical performance test. And we have enrolled over 80 CAR-T patients across two university hospitals in Germany. And the testing includes the 10-meter walking test, measuring gait speed as a marker of mobility, and a 30-second sit-to-stand test, quantifying lower extremity strength by counting the number of repetitions a patient can perform. And in addition, CT-based volumetric body composition was performed using a Ship-AI algorithm that allows automated quantification of adipose tissue, bone, and muscle compartments, which is relevant for sarcopenia. And so the test results were evaluated using sex and age-adjusted reference values, and patients who passed both tests were qualified as or classified as fit, and patients who failed one or both tests as unfit. 

And looking at our study cohort, we see that unfit patients showed a significantly higher baseline inflammatory profile reflected by elevated CRP and ferritin at start of lymphodepletion. Very importantly, when we compare objective fitness with ECOG performance status, we observed substantial heterogeneity within the same ECOG categories. So most patients had an ECOG score of one, over 70% of our cohort, yet their objective physical performance varied significantly. Importantly, objective fitness showed only weak correlation with comorbidity burden. So suggesting physical performance represents a distinct dimension not adequately captured by current standard clinical scoring systems. And we then evaluated survival outcomes and stratification by ECOG performance status, which did not meaningfully separate progression-free or overall survival. In contrast, stratification by objective fitness revealed a trend toward improved survival in fit patients, and when combining fitness with sarcopenia by adding the skeletal muscle index, which is an image-based marker of muscle mass, we observed a significant survival advantage for the fit non-sarcopenic patients. So we next asked whether a high-risk phenotype of unfit sarcopenic patient was associated with increased treatment-related toxicities and we did not observe significant differences here. But strikingly, fit patients had a significantly shorter hospitalization duration with a median stay of 16 days compared to 19 days in unfit patients. 

So in summary, objective physical performance testing combined with body composition analysis can help improve risk stratification in CAR-T recipients beyond a standard of care ECOG performance status. And low physical performance and sarcopenia identified a vulnerable subgroup with poorer outcomes and longer hospital stays. So this is relevant for treatment decisions and outpatient care and these measures could help inform guided targeted prehabilitation and rehabilitation strategies. Further validation of course is needed and ultimately interventional studies would be great to see how we can improve fitness for better outcomes in CAR-T recipients.

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