Phase 2 studies of lenalidomide, subcutaneous bortezomib, and dexamethasone as induction therapy in patients with newly diagnosed multiple myeloma.

There are limited prospective data on lenalidomide, subcutaneous bortezomib, and dexamethasone (RsqVd) in transplant-eligible/transplant-ineligible patients with newly diagnosed multiple myeloma. Reliable biomarkers for efficacy and toxicity are required to better tailor therapy. Two parallel studies were conducted by Cancer Trials Ireland (CTI; NCT02219178) and the Dana-Farber Cancer Institute (DFCI; NCT02441686). Patients received four 21-day cycles of RsqVd and could then receive either another 4 cycles of RsqVd or undergo autologous stem cell transplant. Postinduction/posttransplant, patients received lenalidomide maintenance, with bortezomib included for high-risk patients. The primary endpoint was overall response rate (ORR) after 4 cycles of RsqVd. Eighty-eight patients were enrolled and 84 treated across the two studies; median age was 64.7 (CTI study) and 60.0 years (DFCI study), and 59% and 57% had stage II-III disease. Pooled ORR after 4 cycles in evaluable patients was 93.5%, including 48.1% complete or very good partial responses (CTI study: 91.9%, 59.5%; DFCI study: 95.0%, 37.5%), and in the all-treated population was 85.7% (44.0%). Patients received a median of 4 (CTI study) and 8 (DFCI study) RsqVd cycles; 60% and 31% of patients (CTI study) and 33% and 51% of patients (DFCI study) underwent transplant or received further RsqVd induction, respectively. The most common toxicity was peripheral neuropathy (pooled: 68%, 7% grade 3-4; CTI study: 57%, 7%; DFCI study: 79%, 7%). Proteomics analyses indicated elevated kallikrein-6 in good versus poor responders, decreased midkine in good responders, and elevated macrophage inflammatory protein 1-alpha in patients who stopped treatment from neurotoxicity, suggesting predictive biomarkers warranting further investigation.

Embolic complications of direct current cardioversion of atrial arrhythmias: association with low intensity of anticoagulation at the time of cardioversion.

OBJECTIVES: The goal of this study was to identify the factors responsible for embolic complications of direct current (DC) cardioversion of atrial arrhythmias. BACKGROUND: Direct current cardioversion of atrial fibrillation (AF) carries a risk of thromboembolism, which is reduced, but not eliminated, by anticoagulation. The risk of embolism after conversion of atrial flutter is believed to be lower. No series to date has included enough patients receiving anticoagulants or enough patients with atrial flutter to estimate the risk in these groups. METHODS: We reviewed the case records of 1,950 patients who underwent 2,639 attempts at DC cardioversion. RESULTS: Cardioversion was performed within two days of the apparent onset of the arrhythmia in 443 episodes, 352 without subsequent prolonged anticoagulation with one embolic complication. Cardioversion was preceded by warfarin therapy for > or = 3 weeks in 1,932 instances. No embolic complication occurred in 779 attempts performed with an international normalized ratio (INR) of > or = 2.5 (95% confidence limits 0% to 0.48%). Of 756 cases in which the INR was <2.5 or was not measured before conversion, nine were complicated by thromboembolism. Embolism was significantly more common at an INR of 1.5 to 2.4 than at an INR > or = 2.5 (0.93% vs. 0%, p = 0.012). The incidence of embolism after conversion of atrial flutter or tachycardia was similar to that after cardioversion of AF (0.72% vs. 0.46%, p = NS). CONCLUSIONS: The INR should be > or = 2.5 at the time of cardioversion if the duration of AF is uncertain or >2 days. Cardioversion of atrial flutter presents similar risks and requires similar anticoagulation.