Objective: To explore the dynamic changes in serum lipid levels and nutritional status during BCMA-CAR-T-cell therapy in patients with refractory or relapsed multiple myeloma (R/R MM) based on LEGEND-2. Methods: The data of patients with R/R MM who underwent BCMA-CAR-T therapy at our hospital between March 30, 2016, and February 6, 2018, were retrospectively collected. Serum lipid levels, controlled nutritional status (CONUT) score, and other clinical indicators at different time points before and after CAR-T-cell infusion were compared and analyzed. The best cut-off value was determined by using the receiver operator characteristic (ROC) curve. The patients were divided into high-CONUT score (>6.5 points, malnutrition group) and low-CONUT score groups (≤6.5 points, good nutrition group), comparing the progression-free survival (PFS) and total survival (OS) of the two groups using Kaplan-Meier survival analysis. Results: Before the infusion of CAR-T-cells, excluding triglycerides (TG), patients' serum lipid levels were lower than normal on average. At 8-14 d after CAR-T-cell infusion, serum albumin (ALB), total cholesterol (TC), high-density lipoprotein (HDL), low-density lipoprotein (LDL), and apolipoprotein A1 (Apo A1) levels dropped to the minimum, whereas CONUT scores reached the maximum. In addition to TG, apolipoprotein B (Apo B) levels increased compared with baseline. After CAR-T-cell therapy, the patients' serum lipid levels significantly increased with well-improved nutritional status. Spearman's related analysis showed that TC, HDL, and ApoA1 levels after CAR-T-cell injection were significantly negatively correlated with the grade of cytokine-release syndrome (CRS) (r=-0.548, P=0.003; r=-0.444, P=0.020; r=-0.589, P=0.001). Furthermore, survival analysis indicated that the CONUT score was unrelated to PFS, and the median OS of patients with R/R MM in the high-CONUT score group was shorter than that in the low-CONUT score group (P=0.046) . Conclusions: During CAR-T-cell therapy, hypolipidemia and poor nutritional status were aggravated, which is possibly related to CRS. The patients' serum lipid levels and nutritional status were significantly improved after CAR-T-cell treatment. The CONUT score affected the median OS in patients treated with CAR-T-cells. Therefore, specific screening and intervention for nutritional status in patients receiving CAR-T-cell therapy are required.
目的： 基于LEGEND-2研究探讨BCMA-CAR-T细胞治疗难治复发性多发性骨髓瘤（R/R MM）期间血清脂质水平和营养状态的变化。 方法： 以2016年3月至2018年2月在西安交通大学第二附属医院行BCMA-CAR-T细胞治疗的57例R/R MM患者为研究对象，回顾性分析CAR-T治疗前后不同时间点的血清脂质水平、控制营养状况（CONUT）评分等临床指标的变化。通过ROC曲线确定最佳截断值，将患者分为高CONUT评分组（>6.5分，营养状况不良组）和低CONUT评分组（≤6.5分，营养状况良好组），通过Kaplan-Meier生存分析对比两组的无进展生存（PFS）期及总生存（OS）期。 结果： 输注CAR-T细胞前，患者血清脂质水平除甘油三酯（TG）外均低于正常水平。在CAR-T细胞输注后8~14 d内，血清白蛋白（ALB）、总胆固醇（TC）、高密度脂蛋白（HDL）、低密度脂蛋白（LDL）和载脂蛋白A1（Apo A1）水平降至最低，CONUT评分达到最大值，而TG、载脂蛋白B（Apo B）水平较输注前升高。CAR-T细胞治疗后，患者的血清脂质水平显著升高，同时营养状态显著改善。Spearman相关分析显示，CAR-T细胞输注后TC、HDL和Apo A1的水平与细胞因子释放综合征（CRS）分级呈显著负相关（r＝-0.548，P＝0.003；r＝-0.444，P＝0.020；r＝-0.589，P＝0.001）。生存分析提示，输注前的CONUT评分与PFS无关，高CONUT评分组MM患者较低CONUT评分组患者的中位OS期缩短（P＝0.046）。 结论： CAR-T细胞治疗期间患者的血脂水平降低及营养状态不良加剧，这可能与CRS有关；CAR-T细胞治疗后患者血脂水平及营养状态会显著改善。营养状况CONUT评分是影响CAR-T细胞治疗患者OS的因素。.
Keywords: CONUT score; Chimeric antigen receptor T cell; Multiple myeloma; Nutritional status; Prognostic factors; Serum lipid level.