ORISE Fellow, Office of Oncologic Diseases, Center for Drug Evaluation and Research (CDER), U.S. Food and Drug Administration (U.S. FDA), Silver Spring, MD, USA; Department of Pharmaceutical Care and Health Systems, University of Minnesota - College of Pharmacy, Minneapolis, MN, USA.
LUNGevity Foundation, Chicago, IL, USA.
J Geriatr Oncol. 2024 Mar;15(2):101681. doi: 10.1016/j.jgo.2023.101681. Epub 2023 Dec 16.
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).
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.
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).
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.
虚弱评估可能有助于识别多发性骨髓瘤患者中治疗相关毒性、因毒性而早期停止治疗以及死亡风险最高的患者。我们旨在比较患者报告的虚弱表型（PRFP）和改良版国际骨髓瘤工作组虚弱指数（IMWG FI）在复发/难治性多发性骨髓瘤（RRMM）患者队列中的优势、局限性和虚弱分类。
数据来自 2010 年至 2021 年期间提交给食品和药物管理局进行监管审查的六项 RRMM 三期随机临床试验。使用 PRFP 和 IMWG FI 替代物对患者进行分类为健康、中度健康/虚弱前期或虚弱。使用加权 Cohen's kappa 评估两种方法在患者虚弱分类方面的一致性。生成列联表和韦恩图，以分析不同严重程度组患者虚弱分类的重叠情况。使用描述性统计来总结和比较根据 PRFP 和 IMWG FI 替代物分类为虚弱的患者的临床和人口统计学特征。
在本分析纳入的 2750 名患者中，IMWG FI 替代物将 16.4%（452 名）患者分类为虚弱，28.1%（772 名）为中度健康/虚弱前期，55.5%（1526 名）为健康。同时，PRFP 将 21.7%（597 名）的患者分类为虚弱，24.5%（675 名）为中度健康/虚弱前期，53.8%（1478 名）为健康。PRFP 和 IMWG FI 替代物之间观察到适度的一致性（加权 Cohen's Kappa=0.34[0.31-0.37]）。平均而言，根据 IMWG FI 替代物分类为虚弱的患者比根据 PRFP 分类为虚弱的患者年龄更大，Charlson 合并症指数评分更高。相比之下，根据 PRFP 分类为虚弱的患者的 EORTC QLQ-C30 身体功能量表总分比 IMWG FI 替代物虚弱组的患者差（中位数为 40 分，而 100 分中的 47 分）。
我们的分析发现 IMWG FI 替代物和 PRFP 之间存在适度的一致性。这表明，虽然两种虚弱模型都测量相同的潜在结构，但构成每种方法的变量可能导致同一患者的虚弱分类不同。需要进一步的前瞻性研究来确定和比较不同虚弱指数在 MM 中的预测和预后能力。
