体重指数、给药策略与免疫检查点抑制剂疗效的关系。
Association between body mass index, dosing strategy, and efficacy of immune checkpoint inhibitors.
机构信息
School of Medicine, The University of Texas Southwestern Medical Center, Dallas, Texas, USA.
Department of Internal Medicine (Division of Hematology-Oncology), The University of Texas Southwestern Medical Center, Dallas, Texas, USA.
出版信息
J Immunother Cancer. 2021 Jun;9(6). doi: 10.1136/jitc-2021-002349.
BACKGROUND
Increased body mass index (BMI) has been associated with improved response to immune checkpoint inhibitors (ICIs) in multiple cancer types. We evaluated associations between BMI, ICI dosing strategy, and clinical outcomes.
METHODS
We abstracted clinical data on patients with cancer treated with ICI, including age, sex, cancer type, BMI, ICI type, dosing strategy (weight-based or fixed), radiographic response, overall survival (OS), and progression-free survival (PFS). We compared clinical outcomes between low-BMI and high-BMI populations using Kaplan-Meier curves, Cox regressions, and Pearson product-moment correlation coefficients.
RESULTS
A total of 297 patients were enrolled, of whom 40% were women and 59% were overweight (BMI≥25). Of these, 204 (69%) received fixed and 93 (31%) received weight-based ICI dosing. In the overall cohort, overweight BMI was associated with improved PFS (HR 0.69; 95% CI 0.51 to 0.94; p=0.02) and had a trend toward improved OS (HR 0.77; 95% CI 0.57 to 1.04; p=0.08). For both endpoints, improved outcomes in the overweight population were limited to patients who received weight-based ICI dosing (PFS HR 0.53; p=0.04 for weight-based; vs HR 0.79; p=0.2 for fixed dosing) (OS HR 0.56; p=0.03 for weight-based; vs HR 0.89; p=0.54 for fixed dosing). In multivariable analysis, BMI was not associated with PFS or OS. However, the interaction of BMI≥25 and weight-based dosing had a trend toward association with PFS (HR 0.53; 95% CI 0.26 to 1.10; p=0.09) and was associated with OS (HR 0.50; 95% CI 0.25 to 0.99; p=0.05). Patients with BMI<25 tended to have better outcomes with fixed-dose compared with weight-based ICI, while patients with BMI≥25 tended to have better outcomes with weight-based ICI, although these differences did not achieve statistical significance. There was no association between radiographic response and BMI with fixed-dose ICI (p=0.97), but a near-significant trend with weight-based ICI (p=0.1). In subset analyses, the association between BMI, ICI dosing strategy, and clinical outcomes appeared limited to men.
CONCLUSIONS
The clinical benefit of ICI in high-BMI populations appears limited to individuals receiving weight-based ICI dosing. Further research into optimal ICI dosing strategies may be warranted.
背景
多项癌症类型的研究表明，体重指数（BMI）增加与免疫检查点抑制剂（ICI）的反应改善有关。我们评估了 BMI、ICI 给药方案与临床结局之间的关联。
方法
我们提取了接受 ICI 治疗的癌症患者的临床数据，包括年龄、性别、癌症类型、BMI、ICI 类型、给药方案（基于体重或固定剂量）、影像学反应、总生存期（OS）和无进展生存期（PFS）。我们使用 Kaplan-Meier 曲线、Cox 回归和 Pearson 积矩相关系数比较了低 BMI 和高 BMI 人群的临床结局。
结果
共纳入 297 例患者，其中 40%为女性，59%为超重（BMI≥25）。其中，204 例（69%）接受固定剂量 ICI，93 例（31%）接受基于体重的 ICI 给药。在总体队列中，超重 BMI 与改善的 PFS 相关（HR 0.69；95%CI 0.51 至 0.94；p=0.02），并且 OS 有改善趋势（HR 0.77；95%CI 0.57 至 1.04；p=0.08）。对于这两个终点，超重人群的改善结果仅限于接受基于体重的 ICI 给药的患者（PFS HR 0.53；p=0.04 用于基于体重的；vs HR 0.79；p=0.2 用于固定剂量）（OS HR 0.56；p=0.03 用于基于体重的；vs HR 0.89；p=0.54 用于固定剂量）。多变量分析显示，BMI 与 PFS 或 OS 无关。然而，BMI≥25 和基于体重的给药之间的相互作用与 PFS 呈趋势相关（HR 0.53；95%CI 0.26 至 1.10；p=0.09），与 OS 相关（HR 0.50；95%CI 0.25 至 0.99；p=0.05）。与基于体重的 ICI 相比，BMI<25 的患者倾向于固定剂量 ICI 治疗获得更好的结局，而 BMI≥25 的患者倾向于基于体重的 ICI 获得更好的结局，但这些差异没有达到统计学意义。与固定剂量 ICI 相比，BMI 与基于体重的 ICI 之间的影像学反应没有关联（p=0.97），但与基于体重的 ICI 有接近显著的趋势（p=0.1）。在亚组分析中，BMI、ICI 给药方案与临床结局之间的关联似乎仅限于男性。
结论
高 BMI 人群中 ICI 的临床获益似乎仅限于接受基于体重的 ICI 给药的个体。可能需要进一步研究最佳的 ICI 给药方案。
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