CML

Chimeric Antigen Receptor (CAR) T-cell therapy has emerged as a revolutionary treatment for patients with refractory or relapsed B-cell malignancies specifically referred to as B-cell acute lymphoblastic leukemia (B-ALL). However, a significant proportion of patients experience negative outcomes, including severe inflammatory toxicities and relapse.

Cachexia and malnutrition are known secondary syndromes in many patients with cancer, attributed to the effects of active malignancy, systemic inflammation, and cumulative treatment burden; however, further research is required to accurately characterize these issues in patients with CAR T-cell.

B. Cucchiaro and the team aimed to explore the changes in nutritional status (malnutrition and cachexia) in CAR T-cell therapy patients and the potential impact on patient outcomes including survival. Additionally, they described the utilization of dietetic resources in this specific patient population in a London tertiary referral center.

They performed an inclusive analysis of adult hematology patients receiving licensed CD19-targeting CAR T-cell therapy. Data were collected from the time of treatment consent through to the day of discharge, including body weight, C-reactive protein, albumin, lactate dehydrogenase, nutrition-risk screening scores (hospital-specific), and dietetic input.

Clinical outcomes such as 12-month all-cause mortality, intensive care unit (ICU) admission, high-grade toxicities, and length of hospital stay (LoS) were also recorded. Cachexia and malnutrition were defined using the modified Glasgow Prognostic Score (mGPS) and Global Leadership Initiative on Malnutrition (GLIM) consensus, respectively.

About 114 patients (55.6 ± 15.1 years; 57% males) with B-cell non-Hodgkin’s lymphoma (n = 109) and B-ALL (n = 5), receiving axicabtagene ciloleucel (n = 89) and tisagenlecleucel (n = 25) were included. The median LoS for treatment was 34 (27-38) days. Prior to treatment, 31.5% of patients developed malnutrition, with pre-cachexia/refractory cachexia (mGPS) identified in 43.6% of patients.

This altered nutritional status pre-treatment was significantly associated with adverse patient outcomes post-infusion; mGPS was independently associated with inferior overall survival (OS) (HR = 3.158, CI = 1.36-7.323, P = 0.007), with malnutrition and mGPS associated with increased LoS (P = 0.037), sepsis (P = 0.022), and ICU admission (P = 0.039).

During admission, patients experienced significant body weight loss (-5.6% (-8.8 to -2.4); P < 0.001), with 68.4% developing malnutrition. Malnutrition screening during admission identified 57% of patients at risk, with 66.6% of patients referred to dietetics; however, there was a lack of malnutrition screening and dietetic referrals prior to treatment.

The study concluded that pre-treatment malnutrition and cachexia were significantly associated with adverse CAR T-cell therapy outcomes, with mGPS cachexia status independently linked to inferior OS. Further research in this novel area is essential to confirm the extent and impact of nutritional issues, assist with implementing dietetic pathways, and identify potential interventions to optimize outcomes.

The study received no funds and was in part supported by the Clinical Academic Pathway provided through the CNMAR.

Source: https://pubmed.ncbi.nlm.nih.gov/38901943/

Cucchiaro B, Davies NA, Weekes CE, et al. (2024). “Malnutrition and cachexia are associated with poor CAR T-cell therapy outcomes including survival.” Clin Nutr ESPEN. 2024 Aug;62:206-215. doi: 10.1016/j.clnesp.2024.05.020. Epub 2024 May 28. PMID: 38901943.