Multicenter evaluation of the addition of eltrombopag to immunosuppressive therapy for adults with severe aplastic anemia.

Eltrombopag has been shown to improve response rates when added to standard therapy in adults with severe aplastic anemia in controlled trial settings. However, outcomes in real-world populations have mostly been examined in small retrospective studies. This robust, multicenter, retrospective cohort study across six academic health systems compared outcomes in patients who received immunosuppressive therapy with or without eltrombopag. The study included 82 patients who received front-line therapy from January 2014 to August 2021. Overall response rates at 6 months did not differ significantly for patients receiving eltrombopag versus immunosuppressive therapy alone (58% v. 65%, p = 0.56). However, complete response rates at 6 and 12 months were over two times higher in the eltrombopag arm (29% v. 12%, p = 0.06 and 48% v. 18%, p = 0.005). Rates of hepatotoxicity were similar across both arms. Eltrombopag addition did not impact overall survival (median not reached in either arm at 2 years, p = 0.86) or disease-free survival (median not reached v. 13.3 months at 2 years, p = 0.20). Eltrombopag may not produce as large of a benefit in real-world settings compared to controlled trial settings but may offer patients deeper responses with similar rates of toxicity to immunosuppressive therapy alone.

Real-world assessment of isocitrate dehydrogenase inhibitor-associated differentiation syndrome.

Ivosidenib and enasidenib are targeted agents that inhibit mutant isocitrate dehydrogenase (IDH) enzymes, restoring normal cellular differentiation in affected acute myeloid leukemia patients. Both agents carry a risk of differentiation syndrome (DS), a potentially life-threatening complication. In this multicenter, retrospective study we sought to determine the real-world incidence and characterize DS in patients with a myeloid malignancy treated with an IDH inhibitor. Of 49 total patients, 15 patients (31%) had a documented diagnosis of DS and 8 patients (16%) met the criteria of DS by Montesinos, et al. The most common signs and symptoms of DS were dyspnea/hypoxia (56%), unexplained fever (56%), bone pain/arthralgia (44%), edema/weight gain (39%), and pleural/pericardial effusions (33%). Our study reports a higher real-world incidence of DS in patients treated with IDH inhibitors for myeloid malignancies than previously reported.

Clinical efficacy of 12-h metronidazole dosing regimens in patients with anaerobic or mixed anaerobic infections.

Traditional metronidazole dosing regimens utilize an every 8 h dosing strategy to treat anaerobic and mixed anaerobic infections. However, pharmacokinetic data demonstrate that the half-life of metronidazole is 8-12 h and blood levels at 12 h exceed the in vitro minimum inhibitory concentration (MIC) for most anaerobic infections. The primary objective of this study was to evaluate the frequency of clinical cure among patients who received metronidazole every 12 h compared with those who received an every 8 h frequency. Secondary endpoints included duration of antibiotics, hospital length of stay, escalation of antibiotic therapy, microbiologic cure, and mortality. METHODS: This retrospective, single-center, pre-post intervention study of 200 patients between June 2014 to July 2016. RESULTS: No significant differences in clinical cure for every 12 h versus every 8 h metronidazole dosing regimens (85% for both groups, p = 1.00) were found. There were no differences in any of the secondary endpoints, with a mean duration of antibiotic therapy being 5.9 versus 5.8 days and a hospital length of stay averaging 8.1 versus 6.7 days for the 12- and 8-h dosing groups, respectively (p > 0.05). DISCUSSION: Findings validate pharmacokinetic data suggesting that an extended metronidazole dosing interval effectively treats anaerobic infections.