Association of early disease progression and very poor survival in the GALLIUM study in follicular lymphoma: benefit of obinutuzumab in reducing the rate of early progression
Association of early disease progression and very poor survival in the GALLIUM study in follicular lymphoma: benefit of obinutuzumab in reducing the rate of early progression
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DOI：
10.3324/haematol.2018.209015
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发表时间：
2019-05-31
期刊：
影响因子：
10.1
通讯作者：
Hiddemann, Wolfgang
中科院分区：
文献类型：
--
作者：
Seymour, John F.;Marcus, Robert;Hiddemann, Wolfgang
我们评估了 GALLIUM 中未经治疗的滤泡性淋巴瘤患者的早期疾病进展及其对总生存期 (OS) 的影响（clinicaltrials.gov 标识符：01332968），并研究了两个随机组（基于 obinutuzumab 与基于利妥昔单抗的免疫化疗）对早期疾病进展的影响。使用特定原因的 Cox 回归来评估治疗对随机分组后 24 个月内疾病进展或因疾病进展而死亡的风险的影响，并分析 24 个月后有或没有疾病进展的患者的 OS。随机分组后 6、12 和 18 个月（中位随访时间为 41 个月）对两组的死亡率进行了分析。与利妥昔单抗（601 名中的 57 名）免疫化疗患者相比，奥比妥珠单抗（601 名中的 57 名）发生的早期疾病进展事件较少，平均风险降低了 46.0%（95% CI：25.0-61.1%；累积发病率 10.1% 对比 17.4%）。在中位进展后随访 22.6 个月时，进展事件后死亡风险显着增加 [时变进展状态的 HR，25.5 (95% CI: 16.2-40.3)]。患者在前 24 个月内病情进展越早，死亡风险就越高。 24 个月后，有疾病进展的存活患者与无疾病进展的患者相比，年龄调整后的 OS HR 为 12.2（95% CI：5.6-26.5）。治疗组的进展后生存率相似。总之，相对于利妥昔单抗加化疗，奥比妥珠单抗加化疗与早期疾病进展事件发生率显着降低相关。滤泡性淋巴瘤患者的早期疾病进展与预后不良相关，早期进展后死亡风险更高。进展后生存似乎不受治疗组的影响。
We evaluated early disease progression and its impact on overall survival (OS) in previously untreated follicular lymphoma patients in GALLIUM (clinicaltrials.gov identifier: 01332968), and investigated the effect on early disease progression of the two randomization arms: obinutuzumab-based versus rituximab-based immunochemotherapy. Cause-specific Cox regression was used to estimate the effect of treatment on the risk of disease progression or death due to disease progression within 24 months of randomization and to analyze OS in patients with or without disease progression after 24 months. Mortality in both groups was analyzed 6, 12, and 18 months post randomization (median follow up, 41 months). Fewer early disease progression events occurred in obinutuzumab (57 out of 601) versus rituximab (98 out of 601) immunochemotherapy patients, with an average risk reduction of 46.0% (95% CI: 25.0-61.1%; cumulative incidence rate 10.1% vs. 17.4%). At a median post-progression follow up of 22.6 months, risk of mortality increased markedly following a progression event [HR of time-varying progression status, 25.5 (95% CI: 16.2-40.3)]. Mortality risk was higher the earlier patients progressed within the first 24 months. Age-adjusted HR for OS after 24 months in surviving patients with disease progression versus those without was 12.2 (95% CI: 5.6-26.5). Post-progression survival was similar by treatment arm. In conclusion, obinutuzumab plus chemotherapy was associated with a marked reduction in the rate of early disease progression events relative to rituximab plus chemotherapy. Early disease progression in patients with follicular lymphoma was associated with poor prognosis, with mortality risk higher after earlier progression. Survival post progression did not seem to be influenced by treatment arm.