Nutritional status alterations after chimeric antigen receptor T cell therapy in patients with hematological malignancies: a retrospective study

Abstract

Purpose: The in uence of innovative chimeric antigen receptor T cell (CAR-T) therapy for hematological malignancies on nutritional status remains unknown. Therefore, we aim to explore the alterations of nutritional status after CAR-T therapy in patients with hematological malignancies. Methods: We retrospectively collected the data of patients with acute leukemia (AL), lymphoma and multiple myeloma (MM), who underwent CAR-T therapy at our hospital from 2018 to 2020. The serum albumin, triglyceride and cholesterol before and 7, 14 and 21 days after CAR-T cells infusion were compared and analyzed.Result: A total of 117 patients were enrolled, consisting of 39 AL, 23 lymphoma and 55 MM patients. The baseline albumin, triglyceride and cholesterol were 37.43±5.08 mg/L, 1.63±0.74 mmol/L and 3.62±1.03 mmol/L, respectively. The lowest albumin level was found at 7 days after CAR-T infusion compared with baseline (P<0.001), while the levels of triglyceride increased at 14 and 21 days (P<0.001, P=0.036). The levels of cholesterol at 7, 14, 21 days after CAR-T infusion were lower than baseline (all P<0.05).Spearman correlation coe cient showed cytokine release syndrome grade was negatively correlated with the levels of albumin at 7 days and cholesterol at 21 days after CAR-T infusion (r=-0.353, P<0.001; r=-0.395, P=0.002).Conclusion: Serum albumin and total cholesterol concentration decreased at the lowest level 7 days after CAR-T cells infusion, while triglyceride increased at 14 and 21 days after infusion. The levels of albumin and total cholesterol after CAR-T cells infusion were negatively correlated with the grade of cytokine release syndrome.

The nutritional impact of CD19‐targeted CAR‐T therapy versus BEAM chemotherapy for adult patients with lymphoma

“…The prevalence of neurotoxicity in our CAR‐T cohort concur with the lower rates reported among CAR‐T trials in NHL, ranging from 20% to 64% 43,44 . A previous retrospective audit identified that 18% of patients with neurotoxicity ( n = 4) had on average 8.8% weight loss and all required EN 17 . The present study has implicated that neurotoxicity was associated with weight loss of 6 kg within a 30‐day period post‐treatment, indicating a need to support these patients dietetically.…”

“…16 Another study measured changes in nutrition-related biochemical markers (albumin, triglycerides and cholesterol) during CAR-T therapy, which are not reliable markers of acute nutrition status or body composition changes. 17,18 However, preliminary audit data collected at King's College Hospital based on 40 adults with NHL identified 25% of patients to be malnourished pre-CAR-T therapy, whereas 67% of patients were not impacted by ≥ 5% weight loss of body weight during their hospital admission following CAR-T therapy. 19 The lower prevalence of weight loss was likely attributed by an observed lower prevalence of NIS following CAR-T therapy compared to other treatments.…”

“…One retrospective study found that 37 (out of 132) patients experienced gastrointestinal side‐effects as a direct consequence of CAR‐T therapy, with 100% experiencing diarrhoea, 49% experiencing nausea and vomiting, and 41% experiencing abdominal pain 16 . Another study measured changes in nutrition‐related biochemical markers (albumin, triglycerides and cholesterol) during CAR‐T therapy, which are not reliable markers of acute nutrition status or body composition changes 17,18 . However, preliminary audit data collected at King's College Hospital based on 40 adults with NHL identified 25% of patients to be malnourished pre‐CAR‐T therapy, whereas 67% of patients were not impacted by ≥ 5% weight loss of body weight during their hospital admission following CAR‐T therapy 19 .…”

Cholesterol efflux from C1QB-expressing macrophages is associated with resistance to chimeric antigen receptor T cell therapy in primary refractory diffuse large B cell lymphoma

“…In a mouse mesothelin-expressing pancreatic carcinoma model, the inhibition of cholesterol acyltransferase 1 (ACAT-1) in CAR-T cells resulted in significant tumor regression 46 . Cholesterol levels were reduced after CAR-T cell infusion in several hematological malignancies, suggesting that cholesterol metabolism may impact CAR-T cell therapy 47 . In ovarian cancer cells, membrane cholesterol efflux drives TAM-mediated tumor progression 26 , 48 .…”

Cytokine release syndrome was an independent risk factor associated with hypoalbuminemia for patients with relapsed/refractory hematological malignancies after CAR-T cell therapy

“…The multivariate analysis has confirmed that CRS is an independent risk factor of post-CAR-T hypoalbuminemia. Meanwhile, our previous retrospective study has also found that the albumin level and total cholesterol level after CAR-T cell infusion was negatively correlated with CRS grades [ 13 ]. Therefore, we reasonably hypothesized that a unique mechanism exists wherein CRS contributes to post-CAR-T hypoalbuminemia.…”