A phase 2 trial of CD24Fc for prevention of graft-versus-host disease.

ABSTRACT: Patients who undergo human leukocyte antigen-matched unrelated donor (MUD) allogeneic hematopoietic stem cell transplantation (HSCT) with myeloablative conditioning for hematologic malignancies often develop acute graft-versus-host disease (GVHD) despite standard calcineurin inhibitor-based prophylaxis in combination with methotrexate. This trial evaluated a novel human CD24 fusion protein (CD24Fc/MK-7110) that selectively targets and mitigates inflammation due to damage-associated molecular patterns underlying acute GVHD while preserving protective immunity after myeloablative conditioning. This phase 2a, multicenter study evaluated the pharmacokinetics, safety, and efficacy of CD24Fc in combination with tacrolimus and methotrexate in preventing acute GVHD in adults undergoing MUD HSCT for hematologic malignancies. A double-blind, placebo-controlled, dose-escalation phase to identify a recommended dose was followed by an open-label expansion phase with matched controls to further evaluate the efficacy and safety of CD24Fc in preventing acute GVHD. A multidose regimen of CD24Fc produced sustained drug exposure with similar safety outcomes when compared with single-dose regimens. Grade 3 to 4 acute GVHD-free survival at day 180 was 96.2% (95% confidence interval [CI], 75.7-99.4) in the CD24Fc expansion cohort (CD24Fc multidose), compared with 73.6% (95% CI, 63.2-81.4) in matched controls (hazard ratio, 0.1 [95% CI, 0.0-0.6]; log-rank test, P = .03). No participants in the CD24Fc escalation or expansion phases experienced dose-limiting toxicities (DLTs). The multidose regimen of CD24Fc was well tolerated with no DLTs and was associated with high rates of severe acute GVHD-free survival after myeloablative MUD HSCT. This trial was registered at ClinicalTrials.gov as #NCT02663622.

Chemiresistive Sensor Array with Nanostructured Interfaces for Detection of Human Breaths with Simulated Lung Cancer Breath VOCs.

Timely screening of lung cancer represents a challenging task for early diagnosis and treatment, which calls for reliable, low-cost, and noninvasive detection tools. One type of promising tools for early-stage cancer detection is breath analyzers or sensors that detect breath volatile organic compounds (VOCs) as biomarkers in exhaled breaths. However, a major challenge is the lack of effective integration of the different sensor system components toward the desired portability, sensitivity, selectivity, and durability for many of the current breath sensors. In this report, we demonstrate herein a portable and wireless breath sensor testing system integrated with sensor electronics, breath sampling, data processing, and sensor arrays derived from nanoparticle-structured chemiresistive sensing interfaces for detection of VOCs relevant to lung cancer biomarkers in human breaths. In addition to showing the sensor viability for the targeted application by theoretical simulations of chemiresistive sensor array responses to the simulated VOCs in human breaths, the sensor system was tested experimentally with different combinations of VOCs and human breath samples spiked with lung cancer-specific VOCs. The sensor array exhibits high sensitivity to lung cancer VOC biomarkers and mixtures, with a limit of detection as low as 6 ppb. The results from testing the sensor array system in detecting breath samples with simulated lung cancer VOC constituents have demonstrated an excellent recognition rate in discriminating healthy human breath samples and those with lung cancer VOCs. The recognition statistics were analyzed, showing the potential viability and optimization toward achieving the desired sensitivity, selectivity, and accuracy in the breath screening of lung cancer.

Effect of montelukast for treatment of asthma in cigarette smokers.

OBJECTIVE: Many asthmatic patients are unable to quit cigarettes; therefore information is needed on treatment options for smokers. This study evaluates 10 mg/d montelukast and 250 µg of fluticasone propionate twice daily, each compared with placebo, in patients with self-reported active smoking (unable to quit) and asthma. METHODS: Patients (ages 18-55 years, with asthma [≥1 year], FEV1 of 60% to 90% of predicted value, airway reversibility [≥12%], and self-reported active smoking [≥0.5 to ≤2 packs per day]) were randomized (after a 3-week, single-blind, placebo, run-in period) to 1 of 3 parallel, 6-month, double-blind treatment arms. The primary efficacy end point was the percentage of days with asthma control during treatment. Adverse experiences (AEs) were also evaluated. RESULTS: There were 347, 336, and 336 patients randomized to montelukast, fluticasone, and placebo, respectively. The mean percentage of days with asthma control over 6 months of treatment was 45% (montelukast, P < .05 vs placebo), 49% (fluticasone, P < .001 vs placebo), and 39% (placebo); the difference between montelukast and fluticasone was not significant (P = .14). Patients with a smoking history of ≤11 pack years (the median value) tended to show more benefit with fluticasone, whereas those with a smoking history of >11 pack years tended to show more benefit with montelukast. AEs occurred in similar proportions among treatment groups. CONCLUSIONS: In a population of asthmatic patients actively smoking cigarettes, both 10 mg/d montelukast and 250 µg of fluticasone propionate twice daily significantly increased the mean percentage of days with asthma control compared with placebo.

Efficacy and tolerability of montelukast alone or in combination with loratadine in seasonal allergic rhinitis: a multicenter, randomized, double-blind, placebo-controlled trial performed in the fall.

BACKGROUND: Histamine and cysteinyl leukotrienes seem to be important mediators of allergic rhinitis. OBJECTIVE: This multicenter, randomized, double-blind, parallel-group, placebo-controlled trial evaluated the effectiveness and tolerability of montelukast, loratadine, and combination therapy with montelukast and loratadine for treating patients with fall seasonal allergic rhinitis. METHODS: After a 1-week, single-blind, placebo run-in period, 907 male and female patients aged 15 to 82 years were randomized to 1 of 4 treatments: montelukast 10 mg (n = 155), loratadine 10 mg (n = 301), combination montelukast 10 mg and loratadine 10 mg (n = 302), or placebo (n = 149), administered once daily at bedtime for 2 weeks. The primary endpoint was the daytime nasal symptoms score (mean of congestion, rhinorrhea, pruritus, and sneezing). RESULTS: Mean symptom scores at baseline were similar for the four treatment groups. For each of the three active treatments, the difference was significant for the mean change from baseline compared with placebo (P < or = 0.001). However, the effect of montelukast/loratadine compared with loratadine alone, the primary comparison, was not significantly different. Differences for each therapy alone compared with placebo were also significant for most secondary endpoints, including nighttime symptom scores, eye symptoms scores, and rhinitis-specific quality of life. Differences for montelukast/loratadine compared with each therapy alone generally showed numerical superiority, and a few endpoints showed differences that were statistically significant. All active treatments showed a safety profile generally similar to placebo. CONCLUSIONS: Montelukast alone or in combination with loratadine is well tolerated and provides clinical and quality-of-life benefits for patients with seasonal allergic rhinitis.