New England Journal of Medicine最新文献

Background: B-cell acute lymphoblastic leukemia (B-cell ALL) is the most common childhood cancer. Despite a high overall cure rate, relapsed B-cell ALL remains a leading cause of cancer-related death among children. The addition of the bispecific T-cell engager molecule blinatumomab (an anti-CD19 and anti-CD3 single-chain molecule) to therapy for newly diagnosed standard-risk (as defined by the National Cancer Institute) B-cell ALL in children may improve outcomes.

Methods: We conducted a phase 3 trial involving children with newly diagnosed standard-risk B-cell ALL who had an average or higher risk of relapse. Patients were randomly assigned to receive chemotherapy alone or chemotherapy plus two nonsequential 28-day cycles of blinatumomab. The primary end point was disease-free survival.

Results: The data and safety monitoring committee reviewed the results from the first interim efficacy analysis, which included 1440 patients who had undergone randomization (722 to chemotherapy alone and 718 to blinatumomab and chemotherapy) and recommended early termination of randomization. At a median follow-up of 2.5 years, the estimated 3-year disease-free survival (±SE) was 96.0±1.2% with blinatumomab and chemotherapy and 87.9±2.1% with chemotherapy alone (difference in restricted mean survival time, 72 days; 95% confidence interval, 36 to 108; P<0.001 by stratified log-rank test). The estimated 3-year disease-free survival among patients with an average relapse risk was 97.5±1.3% with blinatumomab and chemotherapy and 90.2±2.3% with chemotherapy alone; among those with a higher relapse risk, the corresponding values were 94.1±2.5% and 84.8±3.8%. Cytokine release syndrome, seizures, and sepsis of grade 3 or higher were rare during blinatumomab cycles, but the overall incidence of nonfatal sepsis and catheter-related infections was significantly higher among patients with an average relapse risk who had been assigned to receive blinatumomab and chemotherapy than among those assigned to receive chemotherapy alone.

Conclusions: Adding blinatumomab to combination chemotherapy in patients with newly diagnosed childhood standard-risk B-cell ALL of average or higher risk of relapse significantly improved disease-free survival. (Funded by the National Institutes of Health and others; AALL1731 ClinicalTrials.gov number, NCT03914625.).

Background: Patients receiving standard treatment for chronic subdural hematoma have a high risk of treatment failure. The effect of adjunctive middle meningeal artery embolization on the risk of treatment failure in this population remains unknown.

Methods: We randomly assigned patients with symptomatic chronic subdural hematoma to undergo middle meningeal artery embolization as an adjunct to standard treatment (embolization group) or to receive standard treatment alone (control group). Either surgical or nonsurgical standard treatment had been chosen for each patient before randomization. The primary efficacy outcome was a composite of the following events: recurrent or residual chronic subdural hematoma (measuring >10 mm) at 180 days; reoperation or surgical rescue within 180 days; or major disabling stroke, myocardial infarction, or death from neurologic causes within 180 days. The primary safety outcome was a composite of major disabling stroke or death from any cause within 30 days.

Results: Among 310 enrolled patients, 149 were randomly assigned to the embolization group and 161 to the control group; 189 patients were to receive surgical standard treatment and 121 nonsurgical standard treatment. The mean age of the patients was 73 years, and 70% were men. In the primary efficacy analysis, a primary-outcome event occurred in 19 of 120 patients (16%) in the embolization group, as compared with 47 of 129 patients (36%) in the control group (odds ratio, 0.36; 95% confidence interval, 0.20 to 0.66; P = 0.001). In the primary safety analysis, 4 of 144 patients (3%) in the embolization group and 5 of 166 patients (3%) in the control group either had a major disabling stroke or died within 30 days. Through 180 days, 12 patients (8%) in the embolization group and 9 patients (5%) in the control group had died, with death from neurologic causes occurring in 1 patient (1%) in the embolization group and in 3 patients (2%) in the control group.

Conclusions: Among patients with symptomatic chronic subdural hematoma, adjunctive middle meningeal artery embolization resulted in a lower risk of treatment failure than standard treatment alone, without resulting in an increased incidence of disabling stroke or death in the short term. Further study of longer-term safety outcomes is warranted. (Funded by Balt USA; STEM ClinicalTrials.gov number, NCT04410146.).