Malnutrition and cachexia are associated with poor CAR T-cell therapy outcomes including survival.

BACKGROUND & AIMS: Chimeric Antigen Receptor (CAR) T-cell therapy has emerged as a revolutionary treatment for patients with refractory or relapsed B-cell malignancies. However, a significant proportion of patients experience negative outcomes, including severe inflammatory toxicities and relapse. Cachexia and malnutrition are known secondary syndromes in many cancer patients, attributed to the effects of active malignancy, systemic inflammation, and cumulative treatment burden; however, further research is required to accurately characterise these issues in CAR T-cell patients. The aims of this service evaluation were 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, we describe the utilisation of dietetic resources in this specific patient population in a London tertiary referral centre. METHODS: Adult haematology patients receiving licensed CD19-targeting CAR T-cell therapy at University College London Hospital between 01/04/19 and 01/09/21 were included. Data were collected from the time of treatment consent, and throughout admission to day of discharge: body weight (BW), 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. RESULTS: 114 patients (55.6 ± 15.1 years; 57% males) with B-cell non-Hodgkin's lymphoma (n = 109) and B-cell acute lymphoblastic leukaemia (n = 5), receiving axicabtagene ciloleucel (n = 89) and tisagenlecleucel (n = 25) were included. 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 (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 BW loss (-5.6% (-8.8 to -2.4); p=<0.001), with 68.4% developing malnutrition. Malnutrition screening during admission identified 57% 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. CONCLUSION: Pre-treatment malnutrition and cachexia was significantly associated with adverse CAR T patient outcomes, including mGPS cachexia status independently associated with inferior overall survival. Further research in this novel space is essential to confirm the extent and impact of nutritional issues, to assist with implementing dietetic pathways, and to identify potential interventions with a view to optimising outcomes.

Systematic review of nutrition support interventions in adult haematology and oncology patients receiving CAR T cell therapy.

BACKGROUND & AIMS: Chimeric Antigen Receptor (CAR) T cell therapy is a novel adoptive immunotherapy that is revolutionising the treatment of haematological malignancies and solid tumours. Maintaining a patient's nutritional status and implementing nutrition support interventions have been shown to improve certain patient outcomes in standard anti-cancer therapies; however, guidance for nutrition support interventions in CAR T cell therapy are lacking. The primary aim of this review was to determine the impact of nutrition support interventions on patient-centred outcomes for adult CAR T cell therapy haematology and oncology patients. The patient-centred outcomes of interest included nutritional status and dietary intake, morbidity, functional status, and mortality. Our secondary aim was to describe the nutrition implications that have been acknowledged (but not fully evaluated) in CAR T cell therapy, and to guide future research and practice. METHODS: Four electronic databases (CENTRAL, Embase, MEDLINE and CINAHL) were searched to January 2021, with additional records identified through handsearching and snowballing. Studies considered eligible for inclusion were randomised control trials (RCT), quasi-RCTs, cohort and observational studies, assessing nutrition support interventions (oral, enteral and/or parenteral) in adult haematology and oncology patients receiving CAR T cell therapy or adoptive immunotherapy. No publication status, year or language restrictions were applied. RESULTS: Two authors reviewed the title and abstracts of 1181 retrieved records; however no studies were eligible for inclusion in this systematic review. CONCLUSIONS: We are currently unable to identify if there is an association between nutrition support interventions and outcomes in CAR T cell therapy for adults with haematological malignancies or solid tumours. Lower quality clinical studies and animal models were identified that permitted us to qualitatively describe the risks for poor nutritional status in this population. This empty review confirms the need for research into the potential impact of nutrition support in CAR T cell therapy, including well-designed RCTs.