Olutasidenib (FT-2102) in patients with relapsed or refractory IDH1-mutant glioma: A multicenter, open-label, phase Ib/II trial.

BACKGROUND: Olutasidenib (FT-2102) is a highly potent, orally bioavailable, brain-penetrant and selective inhibitor of mutant isocitrate dehydrogenase 1 (IDH1). The aim of the study was to determine the safety and clinical activity of olutasidenib in patients with relapsed/refractory gliomas harboring an IDH1R132X mutation. METHODS: This was an open-label, multicenter, nonrandomized, phase Ib/II clinical trial. Eligible patients (≥18 years) had histologically confirmed IDH1R132X-mutated glioma that relapsed or progressed on or following standard therapy and had measurable disease. Patients received olutasidenib, 150 mg orally twice daily (BID) in continuous 28-day cycles. The primary endpoints were dose-limiting toxicities (DLTs) (cycle 1) and safety in phase I and objective response rate using the Modified Response Assessment in Neuro-Oncology criteria in phase II. RESULTS: Twenty-six patients were enrolled and followed for a median 15.1 months (7.3‒19.4). No DLTs were observed in the single-agent glioma cohort and the pharmacokinetic relationship supported olutasidenib 150 mg BID as the recommended phase II dose. In the response-evaluable population, disease control rate (objective response plus stable disease) was 48%. Two (8%) patients demonstrated a best response of partial response and eight (32%) had stable disease for at least 4 months. Grade 3‒4 adverse events (≥10%) included alanine aminotransferase increased and aspartate aminotransferase increased (three [12%], each). CONCLUSIONS: Olutasidenib 150 mg BID was well tolerated in patients with relapsed/refractory gliomas harboring an IDH1R132X mutation and demonstrated preliminary evidence of clinical activity in this heavily pretreated population.

Inclusion-body myositis associated with Alzheimer's disease.

Sporadic inclusion-body myositis (s-IBM) is a myopathy that is characterized by progressive weakness and muscle pathology demonstrating inflammation and rimmed vacuoles. In addition, similar to the pathology observed in the brains of patients with Alzheimer's disease, the deposition of beta-amyloid and phosphorylated tau proteins in muscle fibers has been reported. These shared pathologic features have prompted hypotheses suggesting a shared etiology of these two conditions. We report a case of a 73-year-old woman initially diagnosed with s-IBM who later developed Alzheimer's disease.

Open-label exploration of an intravenous nalbuphine and naloxone mixture as an analgesic agent following gynecologic surgery.

OBJECTIVE: The purpose of this series was to explore a 12.5:1 fixed-dose ratio of an intravenous nalbuphine and naloxone mixture (NNM) for use in patients following gynecologic surgery. DESIGN AND PATIENTS: Open-label, nonrandomized case series. The first series was a dose-ranging investigation for 12 patients following elective total abdominal hysterectomy or myomectomy. In this series, fentanyl was used for intraoperative analgesia, and patients were assigned to a lower NNM (2.5 mg/0.2 mg) or to a higher NNM (5 mg/0.4 mg) dose group. The second series evaluated the fixed dose of 5 mg nalbuphine/0.4 mg naloxone for four patients undergoing ambulatory gynecologic procedures. In the second series, no opioid agents were administered intraoperatively to eliminate the possibility of mu-opioid reversal by naloxone postoperatively. OUTCOME MEASURES: Pain control was assessed using a Verbal Pain Scale (0-10). Vital signs, side effects, and adverse events were recorded to determine drug safety. RESULTS: In the first series, there were no adverse events; however, each patient required rescue medication (either morphine or fentanyl). In the second series, two of the four patients reported a reduction in pain following drug administration and did not require any further analgesic agents in the 3-hour postoperative period. One patient had an asymptomatic lowering of heart rate after receiving the drug. CONCLUSION: Additional research of the unique combination therapy of nalbuphine and naloxone is warranted to further determine its potential clinical efficacy and safety.