Early intervention in myelofibrosis and impact on outcomes: A pooled analysis of the COMFORT-I and COMFORT-II studies

Background

In a pooled analysis of the phase 3 Controlled Myelofibrosis Study With Oral JAK Inhibitor Treatment I (COMFORT-I) and COMFORT-II clinical trials, adult patients with intermediate-2 or high-risk myelofibrosis who received oral ruxolitinib at randomization or after crossover from placebo or best available therapy (BAT) had improved overall survival (OS).

Methods

This post hoc analysis of pooled COMFORT data examined relevant disease outcomes based on the disease duration (≤12 or >12 months from diagnosis) before ruxolitinib initiation.

Results

The analysis included 525 patients (ruxolitinib: ≤12 months, n = 84; >12 months, n = 216; placebo/BAT: ≤12 months, n = 66; >12 months, n = 159); the median age was 65.0–70.0 years. Fewer thrombocytopenia and anemia events were observed among patients who initiated ruxolitinib treatment earlier. At Weeks 24 and 48, the spleen volume response (SVR) was higher for patients who initiated ruxolitinib earlier (47.6% vs. 32.9% at Week 24, p = .0610; 44.0% vs. 26.9% at Week 48, p = .0149). In a multivariable analysis of factors associated with spleen volume reduction, a logistic regression model that controlled for confounding factors found that a significantly greater binary reduction was observed among patients with shorter versus longer disease duration (p = .022). At Week 240, OS was significantly improved among patients who initiated ruxolitinib earlier (63% [95% CI, 51%‒73%] vs. 57% [95% CI, 49%‒64%]; hazard ratio, 1.53; 95% CI, 1.01‒2.31; p = .0430). Regardless of disease duration, a longer OS was observed for patients who received ruxolitinib versus those who received placebo/BAT.

Conclusions

These findings suggest that earlier ruxolitinib initiation for adult patients with intermediate-2 and high-risk myelofibrosis may improve clinical outcomes, including fewer cytopenia events, durable SVR, and prolonged OS.

Plain Language Summary

• Patients with myelofibrosis, a bone marrow cancer, often do not live as long as the general population. These patients may also have an enlarged spleen and difficult symptoms such as fatigue.
• Two large clinical trials showed that patients treated with the drug ruxolitinib lived longer and had improved symptoms compared to those treated with placebo or other standard treatments.
• Here it was examined whether starting treatment with ruxolitinib earlier (i.e., within a year of diagnosis) provided benefits versus delaying treatment.
• Patients who received ruxolitinib within a year of diagnosis lived longer and experienced fewer disease symptoms than those whose treatment was delayed.

     

2019年重庆市30岁及以上人群归因于被动吸烟的肺癌疾病负担研究

目的 分析重庆市肺癌发病死亡和疾病负担归因于被动吸烟的情况,为开展肺癌防治提供建议。 方法 肺癌死亡个案数据来源于2019年重庆市肿瘤登记报告系统,被动吸烟率来自2013年重庆市慢性病及危险因素监测。计算人群归因危险度百分比(population attributable risk percent, PAR%)、被动吸烟导致的肺癌发病、死亡和疾病负担。采用Excel 2010与SPSS 25.0进行统计分析,率的比较采用χ²检验。 结果 2013年30岁及以上成年人被动吸烟率为52.37%。2019年重庆市30岁及以上人群肺癌发病率与标化发病率分别为118.44/10万与80.83/10万,死亡率与标化死亡率分别为96.51/10万、63.58/10万。肺癌发病率和死亡率归因于被动吸烟的PAR%分别为19.76和19.04,归因发病率与归因标化发病率分别为23.41/10万和16.34/10万,归因死亡率与归因标化死亡率分别为18.38/10万和12.40/10万。2019年重庆市30岁及以上肺癌早死所致寿命损失年率(years of life lost,YLL)、残疾所致寿命损失年率(years lived with disability,YLD)、调整伤残寿命损失年率(disability adjusted life year,DALY)分别为21.16‰、0.31‰、21.47‰,YLL率、YLD率、DALY率归因于被动吸烟的PAR%分别为21.16、19.76和20.49,归因YLL率为4.34‰,归因YLD率为0.06‰,归因DALY率为4.40‰。 结论 2019年重庆市30岁及以上人群肺癌发病率、死亡率、YLL率、DALY率高,被动吸烟率高,肺癌归因于被动吸烟的疾病负担重,应加强落实控烟工作。     

Ⅱ型固有淋巴样细胞在嗜酸性粒细胞性慢性鼻窦炎发病机制中的作用研究进展

慢性鼻窦炎(CRS)是一种常见的慢性非特异感染性鼻部疾病,病理分型主要分为Th2细胞介导的嗜酸性粒细胞性鼻窦炎(ECRS)和Th1细胞介导的非嗜酸性粒细胞性鼻窦炎(非ECRS)2种表型。欧洲国家CRS患病人群主要表现为ECRS,而随着亚洲国家的急剧工业化发展,其ECRS的比例也在急剧增加。ECRS发病机制复杂,涉及多种免疫细胞和相关因子相互作用。其治疗方法包括抗生素、激素药物治疗及手术治疗等,但仍有部分患者症状难以改善或存在复发的风险。Ⅱ型固有淋巴样细胞(ILC2s)是一种非B、非T的新型淋巴细胞,与Th2免疫应答关系密切。文章就ILC2s在ECRS发病机制中的作用进行综述,以期为ECRS的诊断和治疗提供理论参考。     

Chalcone hybrids and their antimalarial activity

Malaria, one of the most striking, re-emerging infectious diseases caused by the genus Plasmodium, places a huge burden on global healthcare systems. A major challenge in the control and eradication of malaria is the continuous emergence of increasingly widespread drug-resistant malaria, creating an urgent need to develop novel antimalarial agents. Chalcone derivatives are ubiquitous in nature and have become indispensable units in medicinal chemistry applications due to their diverse biological profiles. Many chalcone derivatives demonstrate potential in vitro and in vivo antimalarial activity, so chalcone could be a useful template for the development of novel antimalarial agents. This review covers the recent development of chalcone hybrids as antimalarial agents. The critical aspects of the design and structure–activity relationship of these compounds are also discussed.