Cook Gordon, Royle Kara-Louise, Pawlyn Charlotte, Hockaday Anna, Shah Vallari, Kaiser Martin F, Brown Sarah R, Gregory Walter M, Child J Anthony, Davies Faith E, Morgan Gareth J, Cairns David A, Jackson Graham H
Leeds Institute of Cancer and Pathology, University of Leeds, Leeds, UK; Clinical Trials Research Unit, Leeds Institute of Clinical Trials Research, University of Leeds, Leeds, UK.
Clinical Trials Research Unit, Leeds Institute of Clinical Trials Research, University of Leeds, Leeds, UK.
Lancet Haematol. 2019 Mar;6(3):e154-e166. doi: 10.1016/S2352-3026(18)30220-5. Epub 2019 Feb 6.
Tolerability of treatments for multiple myeloma can depend on the characteristics of the patient being treated. We aimed to develop and validate a risk profile, using routinely collected data, that could predict overall survival in patients with multiple myeloma who were ineligible for stem-cell transplantation.
We used patient data from two randomised controlled trials done in patients with newly diagnosed multiple myeloma who were ineligible for stem-cell transplantation (the NCRI Myeloma XI study [NCRI-XI, n=1852] and the MRC Myeloma IX study [MRC-IX, n=520]), to develop the UK Myeloma Research Alliance Risk Profile (MRP) for overall survival. We used multivariable Cox regression with a least absolute shrinkage and selection operator penalty term. Multiple imputation by chained equations was used to account for missing data in the development and internal validation of the model. The MRP was internally validated in NCRI-XI and externally validated in MRC-IX. The D-statistic was estimated in the developed model and used to internally and externally validate the model according to prespecified criteria.
The MRP included WHO performance status, International Staging System, age, and C-reactive protein concentration as prognostic variables. The MRP was prognostic of overall survival and was successfully internally validated in NCRI-XI and externally validated in MRC-IX (D-statistic NCRI-XI: 0·840 [95% CI 0·718-0·963] and MRC-IX: 0·654 [0·497-0·811]). The MRP groups defining low-risk, medium-risk, and high-risk patients were associated with progression-free survival and early mortality. A decrease in the percentage of protocol dose delivered and quality of life at baseline were associated with increased risk. The MRP groups remained prognostic in patients exposed to different therapeutic combinations and in patients with genetic high-risk disease defined according to both the UK and International Myeloma Working Group definitions.
We have developed and externally validated a risk profile for overall survival containing widely available clinical parameters. This risk profile could aid decision making in patients with multiple myeloma ineligible for stem-cell transplantation, but further external validation is required.
Medical Research Council, Novartis, Schering Health Care, Chugai, Pharmion, Celgene, Ortho Biotech, Cancer Research UK, Celgene, Merck Sharp & Dohme, and Amgen.
多发性骨髓瘤治疗的耐受性可能取决于接受治疗患者的特征。我们旨在利用常规收集的数据开发并验证一种风险模型，以预测不符合干细胞移植条件的多发性骨髓瘤患者的总生存期。
我们使用了两项针对新诊断的、不符合干细胞移植条件的多发性骨髓瘤患者进行的随机对照试验中的患者数据（英国国家癌症研究所骨髓瘤XI研究 [NCRI-XI，n = 1852] 和医学研究委员会骨髓瘤IX研究 [MRC-IX，n = 520]），来开发用于总生存期的英国骨髓瘤研究联盟风险模型（MRP）。我们使用了带有最小绝对收缩和选择算子惩罚项的多变量Cox回归。通过链式方程进行多重插补，以处理模型开发和内部验证过程中的缺失数据。MRP在NCRI-XI中进行了内部验证，并在MRC-IX中进行了外部验证。在开发的模型中估计D统计量，并根据预先设定的标准用于模型的内部和外部验证。
MRP包括世界卫生组织体能状态、国际分期系统、年龄和C反应蛋白浓度作为预后变量。MRP对总生存期具有预后价值，并在NCRI-XI中成功进行了内部验证，在MRC-IX中进行了外部验证（D统计量，NCRI-XI：0·840 [95%CI 0·718 - 0·963]，MRC-IX：0·654 [0·497 - 0·811]）。定义低风险、中风险和高风险患者的MRP分组与无进展生存期和早期死亡率相关。基线时方案剂量交付百分比的降低和生活质量与风险增加相关。MRP分组在接受不同治疗组合的患者以及根据英国和国际骨髓瘤工作组定义的基因高危疾病患者中仍具有预后价值。
我们开发并在外部验证了一种包含广泛可用临床参数的总生存期风险模型。这种风险模型可为不符合干细胞移植条件的多发性骨髓瘤患者的决策提供帮助，但需要进一步的外部验证。
医学研究委员会、诺华、先灵葆雅医疗保健、中外制药、法玛新、新基、奥多生物科技、英国癌症研究中心、新基、默克雪兰诺和安进。
