Association Between Pretreatment Skeletal Muscle and Outcomes After CAR T-Cell Therapy

Kyuwan Lee, Aleksi Iukuridze, Tianhui He, Alysia Bosworth, Lanie Lindenfeld, Jennifer Berano Teh, Meagan Echevarria, Sophia Albanese, Liezl Atencio, Rusha Bhandari, F. Lennie Wong, Andrew S. Artz, Tanya Siddiqi, Liana Nikolaenko, Jasmine Zain, Matthew Mei, Geoffrey Shouse, Leslie L. Popplewell, Alex F. Herrera, L. Elizabeth BuddeStephen J. Forman, Saro H. Armenian

Research output: Contribution to journalArticlepeer-review

3 Scopus citations

Abstract

Background: The purpose of this study was to examine the association between baseline skeletal muscle measurements, acute toxicity (immune effector cell–associated neurotoxicity syndrome [ICANS], cytokine release syndrome), and treatment efficacy in patients undergoing CAR T-cell therapy for B-lineage lymphoma. Patients and Methods: Skeletal muscle measurements were obtained from automated CT measurements in 226 consecutive patients who received CAR T-cell therapy between 2015 and 2021. The Kaplan-Meier method was used to examine progression-free survival (PFS) and overall survival (OS) at 1-year. Multivariable regression was used to calculate the hazard ratio (HR) with 95% confidence intervals, adjusted for covariates. Results: The median age of the cohort was 63.1 years (range, 18.5–82.4 years), and most patients were male (66%) and had primary refractory disease (58%). Patients with abnormally low skeletal muscle at baseline were at greater risk of ICANS (HR, 1.74; 95% CI, 1.05–2.87) and had longer length of hospitalization (mean 27.7 vs 22.9 days; P,.05) compared with those with normal muscle mass. Abnormal skeletal muscle was independently associated with risk of disease progression (HR, 1.70; 95% CI, 1.11–2.57) and worse survival (HR, 2.44; 95% CI, 1.49–4.00) at 1 year compared with normal skeletal muscle. Individuals who had abnormal skeletal muscle and high lactate dehydrogenase (LDH) levels at baseline had poor 1-year PFS (17%) and OS (12%) compared with those with normal skeletal muscle and LDH levels (72% and 82%, respectively; P,.001). Patients who had abnormal skeletal muscle and LDH levels had a 5-fold risk (HR, 5.34; 95% CI, 2.97–9.62) of disease progression and a 10-fold risk (HR, 9.73; 95% CI, 4.81–19.70) of death (reference: normal skeletal muscle, normal LDH), independent of prior lines of therapy, extent of residual disease at time of CAR T-cell therapy, functional status, or product. Conclusions: This information can be used for risk stratification prior to CAR T-cell therapy or to implement prehabilitation and nutritional optimization before lymphodepletion as well as thereafter. These efforts will be complementary to ongoing efforts toward sustained efficacy after CAR T-cell therapy.

Original languageEnglish
Pages (from-to)373-382
Number of pages10
JournalJNCCN Journal of the National Comprehensive Cancer Network
Volume21
Issue number4
DOIs
StatePublished - Apr 2023

Bibliographical note

Publisher Copyright:
© JNCCN—Journal of the National Comprehensive Cancer Network.

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