Elbe Kliniken Stade-Buxtehude

Targeted therapies (TT) improve outcomes in BRAF-mutant melanoma. Pre-clinical data suggest that anticoagulation (AC) and platelet aggregation inhibition (PAI) may have antitumoral effects. We evaluated the impact of concomitant AC or PAI on outcomes in patients receiving TT. We analyzed 1296 patients with unresectable stage III-IV BRAF-mutant melanoma treated with BRAF plus MEK inhibitors (2016-2024) in the prospective multicenter ADOReg registry. Patients were categorized as receiving no antithrombotic therapy (ATT; n = 1125), PAI (n = 73; acetylsalicylic acid or clopidogrel), or AC (n = 98; direct oral anticoagulants, low-molecular-weight heparin, or vitamin K antagonists). Median follow-up was 1.3 years. Compared with patients without ATT, those receiving AC had significantly improved 12-month progression-free survival (PFS; HR 0.55, 95 % CI 0.39-0.78, p = 0.001) and overall survival (OS; HR 0.35, 95 % CI 0.19-0.64, p = 0.001). Direct oral anticoagulants showed the most pronounced PFS benefit (HR 0.40, 95 % CI 0.25-0.64, p < 0.001). PAI was not associated with a significant difference in PFS, but multivariable Cox regression indicated a reduced hazard of death (HR 0.48, 95 % CI 0.27-0.87, p = 0.015). Concomitant AC, particularly factor Xa-inhibiting direct oral anticoagulants, was associated with improved survival in melanoma patients undergoing TT. These findings support prospective trials evaluating AC as concomitant therapy in advanced melanoma.

Patients with advanced melanoma progressing after immune checkpoint inhibition (ICI) and BRAF/MEK inhibition have limited therapeutic options. In the LEAP-004 trial, pembrolizumab plus lenvatinib demonstrated activity in PD-1-refractory melanoma. The combination has emerged as a potential option when approved therapies have been exhausted; however, real-world evidence regarding its efficacy remains limited. This retrospective, multicenter DeCOG study included patients with advanced melanoma treated with anti-PD-1 plus lenvatinib after failure of anti-PD-1-based therapy at 11 major skin-cancer centers in Germany and Switzerland between October 2020 and March 2025. Overall, 120 patients were analyzed (median age 59 years); 70 % were male and 38 % had an ECOG performance status > 1. Most patients had ≥ 3 metastatic sites (69 %), brain metastases (42 %), and elevated LDH (58 %). Median follow-up was 13.4 months. Patients received a median of two prior systemic therapy lines; 98 % had been pretreated with ipilimumab/nivolumab, and 66 % exhibited primary resistance to prior ICI. The objective response rate was 23 %, with a median duration of response of 10 months; disease control rate was 47 %. Median progression-free survival (mPFS) was 4 months and median overall survival (mOS) was 10 months, with 12-month PFS and OS rates of 17 % and 42 %, respectively. Durable disease control beyond six months was observed in 23 % of patients, with mPFS of 21 months. Grade ≥ 3 treatment-related adverse events occurred in 21 % of patients. In this real-world cohort, anti-PD-1 plus lenvatinib demonstrated meaningful efficacy in a subset of heavily pretreated patients, predominantly in those with BRAF wild-type melanoma.

There was an error regarding the affiliations for Alexander Roesch [...].

Long-term data on the effectiveness and safety of omalizumab for chronic inducible urticaria (CIndU) in large populations are lacking. To evaluate the effectiveness, safety, estimated omalizumab treatment duration and its predictors, as well as differences between CIndU subtypes, in a large long-term CIndU cohort. A multinational multicenter study was conducted at 14 specialized urticaria centres (UCAREs), including all CIndU patients ever treated with omalizumab from 2009 until July 2022. Kaplan-Meier survival and regression analyses were performed. Across 234 CIndU patients (55% female; mean age 37 years), 76% (n = 178) had standalone CIndU and 24% (n = 56) had predominant CIndU plus minor CSU, with an observation period up to 13 years. Most CIndU patients (73%, n = 145/200 with available data on response) had complete/good response to omalizumab treatment, without significant differences between CIndU subtypes. Sixty-two (26%) patients discontinued omalizumab; due to well-controlled disease (47%, n = 29), ineffectiveness (34%, n = 21), side effects (3%, n = 2), combination of ineffectiveness and side effects (3%, n = 2) and other reasons (13%, n = 8). The median estimated omalizumab treatment duration exceeded 5 years (54% drug survival at 5 years) and was mostly determined by well-controlled disease. Higher age predicted a lower chance to discontinue omalizumab due to well-controlled disease (HR 0.969, 95%CI 0.945-0.995). CIndU subtype and presence of minor CSU were not related to response and time until omalizumab discontinuation for any reason. Omalizumab is highly effective and safe in CIndU patients, with long estimated treatment duration mainly reflecting long disease duration. Our data show omalizumab's high potential as treatment in any subtype of CIndU and support its clinical use for these patients.