Lenalidomide in the treatment of anti-myelin-associated glycoprotein neuropathy: A phase 1 study to identify the maximum tolerated dose.

BACKGROUND: Anti-myelin-associated glycoprotein (MAG) neuropathy is a debilitating demyelinating polyneuropathy with no approved therapies. Our primary objective was to ascertain lenalidomide safety and maximum tolerated dose (MTD) in anti-MAG neuropathy. METHODS: This phase 1b, open-label, single-arm, dose-finding trial was conducted from 2019 through 2022. The original design included a dose-escalation/extension phase followed by a dose-expansion phase. Three doses of lenalidomide were evaluated: 10, 15, and 25 mg. The main outcome was the MTD. RESULTS: Eleven patients enrolled (10 men), with a mean age of 67.6 years (SD = 6.18, range 58-77 years) and mean disease duration of 8.5 years (SD = 10.9, range 1-40 years). The study terminated early due to higher-than-expected non-dose-limiting toxicity venous thromboembolism (VTE) events. The calculated MTD was 25 mg (posterior mean of toxicity probability was 0.01 with a 95% credible interval of 0.00, 0.06), but a recommended phase 2 dose of 15 mg was advised. For secondary exploratory outcomes, only EQ-5D (-0.95, 95% CI -1.81 to -0.09) and total IgM (-162 mg/dL, 95% CI -298 to -26) showed signs of improvement by month 12. CONCLUSIONS: Lenalidomide was associated with higher-than-expected VTE events in anti-MAG neuropathy patients, despite a calculated MTD of 25 mg. A recommended phase 2 dose of 15 mg was advised. Lenalidomide did not improve disability or impairment at 12 months, although this study was not powered for efficacy. The risks of long term lenalidomide may outweigh benefit for patients with anti-MAG neuropathy. Any future efficacy study should address VTE risk, as current myeloma guidelines appear inadequate. TRIAL REGISTRATION: Lenalidomide in Anti-MAG Neuropathy: Phase 1b Study, ClinicalTrials.gov Identifier: NCT03701711, https://clinicaltrials.gov/ct2/show/NCT03701711. First submitted October 10, 2018. First patient enrolled in January 2019.

Effect of Preoperative Antianxiety Medications on Blood Pressure and Blood Loss in Total Knee Arthroplasty: A Case-Control Study.

Background: The increasing number of canceled operations in patients undergoing total knee arthroplasty (TKA) due to high blood pressure readings has put a considerable burden on surgeons. In this study, we aim to assess the effect of giving antianxiety drugs preoperatively on maintaining blood pressure (BP) and blood loss for patients undergoing TKA surgery. Methods: This retrospective case-control study included patients who underwent total knee arthroplasty and divided them into two main groups: those who had taken a 3 mg bromazepam oral tablet at the night preoperatively and the control group. The blood pressure of patients was then measured preoperatively (baseline), in the morning of surgery, in the operating room before anesthesia, and during the surgery. The percentage of measured BP was calculated by dividing the measured BP by the baseline, then multiplying by 100. Results: 301 patients were included in our study: 137 received bromazepam and 164 as a control group. The ratio of systolic BP (SBP) in the morning of surgery to the baseline (percentage of morning SBP) decreased significantly in the bromazepam group compared with the controls. The ratio of SBP, in the operating room before anesthesia (percentage of preanesthesia SBP) also decreased significantly in the bromazepam group. However, the percentage of SBP in the middle of surgery did not change significantly. In addition, there was a significant difference change from the baseline in diastolic BP and mean arterial BP between the two groups in the morning of surgery, inside the theatre, and in the middle of the operation. The bromazepam group also showed a significant decrease in blood loss. Conclusion: Preoperative oral antianxiety drugs (bromazepam) helps in controlling hemodynamic changes associated with anxiety, including maintaining BP in well-controlled hypertensive and healthy patients undergoing TKA, and it plays a role in decreasing the total blood loss.