Li Mengyao, Dave Nimita, Salem Ahmed Hamed, Freise Kevin J
AbbVie Inc., North Chicago, IL Current address: Merck and Co., Rahway, NJ Department of Clinical Pharmacy, Ain-Shams University, Cairo, Egypt.
Medicine (Baltimore). 2017 Sep;96(35):e7988. doi: 10.1097/MD.0000000000007988.
Non-Hodgkin lymphoma (NHL) is a group of lymphoproliferative malignancies with varying treatment responses and progression-free survival (PFS) times. The objective of this study was to quantify the effect of treatment and patient-population characteristics on PFS in patients with NHL.
A database was developed from 513 NHL clinical trials reported from 1993 to 2015. Summary-level PFS was obtained from 112 of these trials, which included 155 cohorts and 11,824 patients. Characteristics evaluated for their impact on PFS included cohort treatment, percentage of patients with each NHL subtype, percentage of patients with different numbers of prior treatments, percentage of subjects previously administered rituximab, performance status, disease stage, median age, and sex distribution.
Rituximab, bendamustine, CHOP (cyclophosphamide, doxorubicin, vincristine, and prednisone combination)/CHOP-like, and other nonchemotherapy drugs, aside from bortezomib, prolonged median PFS time 2 to 4-fold. Follicular lymphoma patients had 60% longer median PFS time than mantle cell lymphoma (MCL) patients, while diffuse large B-cell lymphoma patients had a median PFS time that was 25% of MCL patients. Patients who received ≤1 prior treatment had median PFS times > 10-fold longer than patients who received ≥2 prior treatments. The final model predicted the hazard ratio in 75% of the studies within 25% of the observed value and the observed median PFS time of 92% of the studies fell within the predicted 90% confidence intervals.
The developed PFS model predicts the median PFS time and hazard ratio for specific populations and treatment combinations quantitatively and can potentially be extended to link short-term and long-term clinical outcomes.
非霍奇金淋巴瘤（NHL）是一组具有不同治疗反应和无进展生存期（PFS）的淋巴增殖性恶性肿瘤。本研究的目的是量化治疗和患者群体特征对NHL患者PFS的影响。
从1993年至2015年报告的513项NHL临床试验中建立了一个数据库。从其中112项试验中获得了汇总水平的PFS，这些试验包括155个队列和11824名患者。评估其对PFS影响的特征包括队列治疗、各NHL亚型患者的百分比、接受不同次数既往治疗的患者百分比、既往接受利妥昔单抗治疗的受试者百分比、体能状态、疾病分期、中位年龄和性别分布。
除硼替佐米外，利妥昔单抗、苯达莫司汀、CHOP（环磷酰胺、多柔比星、长春新碱和泼尼松联合方案）/类CHOP方案以及其他非化疗药物使中位PFS时间延长了2至4倍。滤泡性淋巴瘤患者的中位PFS时间比套细胞淋巴瘤（MCL）患者长60%，而弥漫性大B细胞淋巴瘤患者的中位PFS时间是MCL患者的25%。接受≤1次既往治疗的患者的中位PFS时间比接受≥2次既往治疗的患者长>10倍。最终模型在75%的研究中预测的风险比在观察值的25%范围内，92%的研究观察到的中位PFS时间落在预测的90%置信区间内。
所建立的PFS模型定量预测了特定人群和治疗组合的中位PFS时间和风险比，并有可能扩展以连接短期和长期临床结果。
