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.

     

同型半胱氨酸对高血压患者脑卒中复发风险的影响

目的探讨高血压合并脑卒中患者的血浆同型半胱氨酸（Hcy）水平与其他危险因素对于脑卒中复发的影响。 方法分析徐州市中心医院心内科和徐州医科大学附属医院神经外科自2012年5月至2013年12月收治的1623例高血压脑卒中患者的基线资料，中位随访4.9年，根据随访事件中是否发生脑卒中分为复发组（312例）与未复发组（1311例）。Kaplan-Meier生存分析比较不同危险因素脑卒中复发率的差异，单因素与多因素Cox回归模型分析影响脑卒中复发的独立危险因素，以及危险因素之间的交互作用。 结果复发组年龄、空腹血糖、Lg Hcy的水平，以及糖尿病、房颤的患病率均高于未复发组（P<0.05）。Kaplan-Meier生存分析显示，糖尿病、房颤、年龄≥60岁、空腹血糖≥7.0 mmol/L、Hcy≥15 μmol/L的脑卒中复发率明显升高（Log-rank检验，P<0.05）。多因素Cox回归模型分析显示，高龄、Lg Hcy水平升高，以及房颤、糖尿病是脑卒中复发的独立危险因素。Lg Hcy分别与糖尿病、空腹血糖、年龄存在交互作用。 结论血浆Hcy水平升高既是高血压合并脑卒中患者卒中复发的独立危险因素，又通过与糖尿病、高龄、空腹血糖水平升高的交互作用显著增加脑卒中复发风险。     

Gray platelet syndrome: Management of perioperative bleeding in redo cardiac surgery

Gray platelet syndrome (GPS) is a rare (<1/1 000 000) and inherited platelet function disorder characterized by macrothrombocytopenia, α-granule deficiency, and hemorrhages. Bleeding intensity does not correlate with platelet count nor with functional test results. We hereby describe the perioperative bleeding prevention and management of a patient with GPS requiring multiple redo cardiac surgeries.