Introduction

Frailty assessments may help to identify patients at highest risk for treatment-related toxicity, early treatment discontinuation due to toxicity, and death in Multiple Myeloma. We aimed to compare the patient-reported frailty phenotype (PRFP) and a modified version of the International Myeloma Working Group frailty index (IMWG FI) in terms of their strengths, limitations, and classification of frailty in a cohort of patients with relapsed/refractory multiple myeloma (RRMM).

Materials and Methods

Data were pooled from six RRMM Phase 3 randomized clinical trials submitted to the Food and Drug Administration for regulatory review between 2010 and 2021. Patients were classified as fit, intermediate fit/pre-frail, or frail using both PRFP and the IMWG FI proxy. Agreement between the two approaches in classification of patient frailty was assessed using weighted Cohen's kappa. A contingency table and Venn diagram were generated to analyze overlap in categorization of patient frailty across the different severity groups. Descriptive statistics were used to summarize and compare the clinical and demographic characteristics of patients categorized as frail by PRFP vs. IMWG FI proxy.

Results

Of the 2,750 patients included in this analysis, IMWG FI proxy classified 16.4% (452) patients as frail, 28.1% (772) as intermediate fit/pre-frail, and 55.5% (1,526) as fit. Meanwhile, PRFP classified 21.7% (597) of patients as frail, 24.5% (675) as intermediate fit/pre-frail, and 53.8% (1478) as fit. Fair agreement was observed between PRFP and IMWG FI proxy (weighted Cohen's Kappa = 0.34 [0.31–0.37]). On average, patients who were categorized as frail by IMWG FI proxy were older and had higher Charlson Comorbidity Index scores than patients classified as frail by PRFP. In contrast, patients who were classified as frail by PRFP had worse EORTC QLQ-C30 Physical Functioning subscale summary scores as compared to patients in the IMWG FI proxy frail group (median score of 40 vs. 47 out of 100).

Discussion

Our analysis found fair concordance between IMWG FI proxy and PRFP. This demonstrates that while both frailty models measure the same underlying construct, the variables that constitute each approach may result in differing frailty categorizations for the same patient. Further prospective studies are needed to establish and compare the predictive and prognostic abilities of the different frailty indices in MM.

中文翻译：

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患者报告的虚弱表型 (PRFP) 与国际骨髓瘤工作组虚弱指数 (IMWG FI) 代理：两种虚弱测量方法之间的比较

 介绍

虚弱评估可能有助于识别多发性骨髓瘤中治疗相关毒性、因毒性而早期停止治疗和死亡风险最高的患者。我们的目的是比较患者报告的虚弱表型 (PRFP) 和国际骨髓瘤工作组虚弱指数 (IMWG FI) 的修改版本，以比较它们在一组复发/难治性骨髓瘤患者中的优点、局限性和虚弱分类。多发性骨髓瘤（RRMM）。

 材料和方法

数据汇集于 2010 年至 2021 年间提交给美国食品药品监督管理局进行监管审查的 6 项 RRMM 3 期随机临床试验。使用 PRFP 和 IMWG FI 代理将患者分为健康、中等健康/虚弱前或虚弱。使用加权科恩卡帕 (Cohen's kappa) 评估两种患者虚弱分类方法之间的一致性。生成列联表和维恩图来分析不同严重程度组患者虚弱分类的重叠。使用描述性统计来总结和比较 PRFP 与 IMWG FI 代理分类为虚弱的患者的临床和人口特征。

 结果

在本次分析中纳入的 2,750 名患者中，IMWG FI 代理将 16.4% (452) 名患者分类为虚弱，28.1% (772) 名患者分类为中度健康/前虚弱，55.5% (1,526) 名患者分类为健康。与此同时，PRFP 将 21.7% (597) 的患者分类为虚弱，24.5% (675) 的患者分类为中度健康/前虚弱，53.8% (1478) 的患者分类为健康。 PRFP 和 IMWG FI 代理之间观察到了公平的协议（加权 Cohen's Kappa = 0.34 [0.31–0.37]）。平均而言，被 IMWG FI 代理分类为虚弱的患者比被 PRFP 分类为虚弱的患者年龄更大，查尔森合并症指数得分更高。相比之下，与 IMWG FI 代表虚弱组的患者相比，被 PRFP 分类为虚弱的患者的 EORTC QLQ-C30 身体功能子量表总分较差（中位得分为 40 分，满分 100 分为 47 分）。

 讨论

我们的分析发现 IMWG FI 代理和 PRFP 之间相当一致。这表明，虽然两种衰弱模型测量相同的基础结构，但构成每种方法的变量可能会导致同一患者的不同衰弱分类。需要进一步的前瞻性研究来建立和比较 MM 中不同衰弱指数的预测和预后能力。