新型药物在老年慢性淋巴细胞白血病和非霍奇金淋巴瘤患者中导致三级或四级毒性的频率和影响（alliance A151611）。
Frequency and impact of grade three or four toxicities of novel agents on outcomes of older patients with chronic lymphocytic leukemia and non-Hodgkin lymphoma (alliance A151611).
机构信息
University of Chicago Comprehensive Cancer Center, Chicago, IL, United States.
Alliance Statistics and Data Center, Mayo Clinic, Rochester, MN, United States.
出版信息
J Geriatr Oncol. 2018 Jul;9(4):321-328. doi: 10.1016/j.jgo.2018.03.018. Epub 2018 Apr 17.
OBJECTIVE
Older patients with cancer suffer from chemotherapy-related toxicities more frequently than younger patients. As novel agents are being used more commonly in chronic lymphocytic leukemia (CLL) and non-Hodgkin lymphoma (NHL), toxicities of these agents in older patients have not been well studied. Further, impact of these toxicities on outcomes in the elderly is unknown. This study aimed to answer both questions.
PATIENTS AND METHODS
We reviewed 14 Alliance for Clinical Trials in Oncology trials that enrolled CLL and/or NHL patients between 2004-2014. Toxicity was assessed per the NCI-CTCAE (version 3-5). Probabilities of experiencing grade three or four hematologic and non-hematologic toxicities were modeled as a function of clinical and disease-related factors using logistic regression.
RESULTS
1199 patients (409 age ≥ 65; 790 age < 65) were analyzed; 438 received only biologic therapy (145 age ≥ 65; 293 age < 65), and 761 received biologic + chemotherapy (264 age ≥ 65; 497 age < 65). The odds of grade three or four hematologic [odds ratio (OR) 1.70; p = 0.009: 95% CI (1.57-1.84)] and non-hematologic toxicities [OR 1.47; p = 0.022; 95% CI (1.39-1.55)] were increased in older patients with CLL, as well as odds of grade three or four non-hematologic toxicities [OR 1.89; p = 0.017; 95% CI (1.64-2.17)] in older patients with NHL. Grade three or four hematologic toxicities were associated with inferior OS and PFS in older patients with NHL [HR 3.14; p = 0.006; 95% CI (2.25-4.39) for OS and 3.06; p = 0.011; 95% CI (2.10-4.45) for PFS], though not in CLL. A prognostic model predicting grade three or four toxicities was also developed.
CONCLUSIONS
CLL and NHL patients ≥ 65 year encounter more toxicities than younger patients even when treated with novel biologic agents. Development of grade three or four hematologic toxicities lead to inferior PFS and OS in NHL but not in CLL.
目的
与年轻患者相比，老年癌症患者更容易出现化疗相关毒性。随着新型药物在慢性淋巴细胞白血病（CLL）和非霍奇金淋巴瘤（NHL）中的应用越来越广泛，这些药物在老年患者中的毒性尚未得到很好的研究。此外，这些毒性对老年人结局的影响尚不清楚。本研究旨在回答这两个问题。
方法
我们回顾了 2004-2014 年间在肿瘤临床研究联盟中登记的 CLL 和/或 NHL 患者的 14 项试验。毒性按照 NCI-CTCAE（第 3-5 版）进行评估。使用 logistic 回归，根据临床和疾病相关因素，对发生 3 级或 4 级血液学和非血液学毒性的概率进行建模。
结果
分析了 1199 例患者（409 例年龄≥65 岁；790 例年龄<65 岁）；438 例仅接受生物治疗（145 例年龄≥65 岁；293 例年龄<65 岁），761 例接受生物治疗+化疗（264 例年龄≥65 岁；497 例年龄<65 岁）。与 CLL 老年患者相比，3 级或 4 级血液学毒性[比值比（OR）1.70；p=0.009：95%可信区间（1.57-1.84）]和非血液学毒性[OR 1.47；p=0.022；95%可信区间（1.39-1.55）]的可能性增加，以及 NHL 老年患者 3 级或 4 级非血液学毒性[OR 1.89；p=0.017；95%可信区间（1.64-2.17）]的可能性增加。3 级或 4 级血液学毒性与 NHL 老年患者的总生存期（OS）和无进展生存期（PFS）较差相关[HR 3.14；p=0.006；95%可信区间（2.25-4.39）为 OS；3.06；p=0.011；95%可信区间（2.10-4.45）为 PFS]，但在 CLL 中则不然。还开发了一种预测 3 级或 4 级毒性的预后模型。
结论
与年轻患者相比，即使接受新型生物药物治疗，CLL 和 NHL 年龄≥65 岁的患者也会出现更多的毒性。3 级或 4 级血液学毒性的发生导致 NHL 的 PFS 和 OS 较差，但在 CLL 中则不然。
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