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Thank you for attending THSNA 2026. The virtual meeting is now closed.
Presentation Details
| Venous Thromboembolism and Bleeding in Advanced Melanoma: A Propensity-Matched Cohort Analysis Comparing First-Line Immunotherapy and Targeted Therapy Furkan Bahar1, Lauren O’Loughlin2, Soravis Osataphan2, Reed Drews2, Rushad Patell2. 1Department of Internal Medicine, Mount Auburn Hospital, Harvard Medical School, Cambridge, MA, USA.2Division of Hematology/Oncology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, USA |
Abstract
Background Melanoma carries a high risk of thrombotic and bleeding complications. Contemporary frontline treatment paradigms for advanced melanoma rely on immunotherapy and targeted therapy (BRAF/MEK inhibitors (MEKi)). These therapies have distinct immunologic and vascular effects with potentially different thrombotic and bleeding risks. However, there are currently no direct comparative data to guide clinical decision making. Methods We conducted a retrospective cohort study of patients >18 years with advanced melanoma (lymph node or distant organ metastasis) using the TriNetX network from 2010-2024. Patients were classified based on first-line systemic therapy (ipilimumab/nivolumab (Ipi/Nivo) or BRAF/MEKi). We excluded anti–PD-1 monotherapy as patients who receive monotherapy are clinically distinct from those who receive combination therapy, which would not allow balancing the groups while matching. Patients with a history of venous thromboembolism (VTE), gastrointestinal (GI) bleeding, or intracranial hemorrhage were excluded to avoid outcome misclassification. To account for potential confounders, we performed (1:1) propensity score matching for demographics, disease burden (metastasis location), comorbidities, and concomitant baseline medication use (antiplatelets/anticoagulants). Primary outcome was composite VTE (including deep vein thrombosis (DVT) and pulmonary embolism (PE)) at 6 months of systemic therapy. Secondary outcomes included: DVT/PE individually, composite and individual bleeding (including GI bleeding, intracranial bleeding), and all-cause mortality. Outcomes were determined using previously validated ICD-9/10 coding algorithms. We calculated 6-month incidence rates for all primary and secondary outcomes. Hazard ratios (HRs) with 95% confidence interval (CI) were calculated using Cox proportional hazards models. A secondary analysis excluding patients on anticoagulation or pre-existing atrial fibrillation was performed. Results Prior to matching, 1,674 patients in Ipi/Nivo group and 1,120 patients in BRAF/MEKi group met inclusion criteria. After matching, there were 987 patients per cohort. All variables were balanced with standardized mean differences ≤ 0.05. (Table 1) At 6 months, incidence of VTE was 6.5% in Ipi/Nivo and 3.7% in BRAF/MEKi group (HR 1.74, 95% CI 1.16–2.61; p=0.006). PE rates were higher with Ipi/Nivo (4.4% vs 2.3%; HR 1.88, 95% CI 1.13–3.11; p=0.013). DVT rates were numerically increased in Ipi/Nivo group (3.3% vs 1.9%; HR 1.74, 95% CI 0.99–3.06; p=0.052), but not statistically significantly different. There was no observed difference in composite bleeding outcomes (7.7% vs 7.3%; p=0.72), or mortality rates (18.2% vs 15.8%; p=0.17) at 6 months for Ipi/Nivo compared to BRAF/MEKi respectively. (Figure 1) In secondary analysis, excluding anticoagulation prior to systemic therapy, there were 718 patients in each matched cohort. Patients treated with Ipi/Nivo had higher VTE (5.8% vs 3.3% HR 1.87, 95% CI 1.10–3.17; p=0.019) and PE (4.3% vs 2.1%, HR 2.24, 95% CI 1.16–4.31; p=0.013) rates compared to BRAF/MEKi. Similar to primary analysis, bleeding and mortality did not differ between groups. Conclusions In adults with advanced melanoma, immunotherapy was associated with significantly higher 6-month risk of VTE compared with BRAF/MEKi with similar bleeding and 6-month mortality rates. These findings highlight the importance of thrombotic risk stratification, regimen selection, and targeted thromboprophylaxis when initiating systemic therapy in patients with high baseline thrombotic and bleeding risk.
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No part of this publication may be reproduced, distributed, or transmitted in any form or by any means, including photocopying, recording, or other electronic or mechanical methods, without the prior written permission of the author.