Patients with pancreatic cancer (PC) carry the highest risk of venous thromboembolism (VTE) amongst all cancer patients. Appropriate use of primary thromboprophylaxis might significantly and safely reduce its burden. We performed a systematic review of published studies and meeting abstracts using MEDLINE and EMBASE through July 2020 to evaluate the efficacy and safety of primary thromboprophylaxis in ambulatory PC patients receiving chemotherapy. The Mantel–Haenszel random effect model was used to estimate the pooled event-based risk ratio (RR) and the pooled absolute risk difference (RD) with a 95% confidence interval (CI). Five randomized controlled studies with 1003 PC patients were included in this meta-analysis. Compared to placebo, thromboprophylaxis significantly decreased the risk of VTE (pooled RR 0.31, 95% CI 0.19–0.51, p < 0.00001, I² = 8%; absolute RD −0.08, 95% CI −0.12–−0.05, p < 0.00001, I² = 0%), with an estimated number needed to treat of 11.9 patients to prevent one VTE event. Similar reductions of VTE were observed in studies with parenteral (RR 0.30, 95% CI 0.17–0.53) versus oral anticoagulants (RR 0.37, 95% CI 0.14–0.99) and in studies using prophylactic doses of anticoagulants (RR 0.34, 95% CI 0.17–0.70) versus supra-prophylactic doses of anticoagulants (RR 0.27, 95% CI 0.08–0.90). The pooled RR for major bleeding was 1.08 (95% CI 0.47–2.52, p = 0.85, I² = 0%) and the absolute RD was 0.00 (95% CI −0.02–0.03, p = 0.85, I² = 0%). Evidence supports a net clinical benefit of thromboprophylaxis in ambulatory PC patients receiving chemotherapy. Adequately powered randomized phase III studies assessing the most effective anticoagulant and the optimal dose, schedule and duration of thromboprophylaxis to be used are warranted.

Direct oral anticoagulants (DOAC) are now recommended for the treatment of cancer-associated thrombosis (CAT) based on the results of dedicated trials demonstrating that DOAC are non-inferior to low molecular weight heparins in preventing recurrent venous thromboembolism (VTE) in this population. The definition of “cancer patient” differs substantially among studies. Whether patients with active cancer and those with a history of cancer (HOC) carry the same risks of recurrent VTE and bleeding remains unclear. Few studies reported data on the efficacy and safety of anticoagulants according to active cancer or HOC categories. While in subgroup analyses of EINSTEIN and HOKUSAI the rates of recurrent VTE and bleeding did not differ between these categories, results from a subgroup analysis of AMPLIFY, from HOKUSAI-Cancer, and from the COMMAND cohort suggest that HOC patients might have a lower bleeding risk than active cancer patients. Whether the inclusion of HOC patients in CAT studies might introduce some bias by decreasing the rates of both recurrent VTE and bleeding remains an unanswered issue since no dedicated prospective study addressed this question. A strict definition of active cancer should be used in further trials.

The Ottawa score (OS) for predicting the risk of recurrent venous thromboembolism (VTE) in cancer patients with VTE may help to guide anticoagulant treatment decisions that will optimize benefit-risk ratios. However, data on its reliability are conflicting. We applied the OS to all cancer patients with VTE enrolled in the prospective multicenter TROPIQUE study who received low-molecular-weight heparin over a 6-month period. Of 409 patients, 171 (41.8%) had a high-risk OS. The 6-month cumulative incidence of recurrent VTE was 7.8% (95%CI 4.2–14.8) in the high-risk OS group versus 4.8% (95%CI 2.6–8.9) in the low-risk OS group (SHR 1.47; 95%CI 0.24–8.55). The Area Under the Receiver Operating Characteristic curve (AUROC) of the OS in identifying patients who developed recurrent VTE was 0.53 (95%CI 0.38–0.65), and its accuracy was 57.9%. Among individual variables included in the OS, only prior VTE was significantly associated with the 6-month risk of recurrent VTE (SHR 4.39; 95% CI 1.13–17.04). When pooling data from all studies evaluating this score for predicting VTE recurrence in cancer patients (7 studies, 3413 patients), the OS estimated pooled AUROC was 0.59 (95%CI 0.56–0.62), and its accuracy was 55.7%. The present findings do not support the use of the OS to assess the risk of recurrent VTE in cancer patients.

Background: Data on the performance of the Khorana, PROTECHT, and ONKOTEV risk assessment models (RAMs) to predict venous thromboembolism (VTE) in patients with pancreatic cancer (PC) receiving outpatient chemotherapy remain limited. We performed a head-to-head comparison of these RAMs in patients with newly diagnosed PC enrolled in the nationwide, multicenter, and prospective BACAP cohort. Methods: The Khorana, PROTECHT, and ONKOTEV scores were calculated at enrollment prior to chemotherapy. Patients were stratified into intermediate- and high-VTE-risk groups according to each RAM. The primary study outcome was VTE at a 6-month follow-up. The accuracy and discriminatory performance of the scores were assessed by calculating time-dependent Brier scores and c-indexes. Sub-distribution hazard ratios (SHRs) between high- and intermediate-risk patients were estimated. Results: Of 762 PC patients, 73 developed VTE within 6 months. In the competing risk analysis, the cumulative incidence of VTE at 6 months was 16.4% (95% CI, 13.8–19.1). The time-dependent Brier score was 0.14 (95% CI, 0.12–0.15) for all scores, indicating well-calibrated predictions. The respective time-dependent c-index of the Khorana, the PROTECHT, and the ONKOTEV scores was 0.50 (95% CI, 0.46–0.55), 0.50 (95% CI, 0.49–0.51), and 0.53 (95% CI, 0.48–0.58), indicating poor discrimination. The SHRs between high- and intermediate-risk patients ranged from 1.05 (95% CI, 0.76–1.44) for the ONKOTEV score to 1.06 (95% CI, 0.77–1.45) for the Khorana score. Conclusion: In newly diagnosed PC patients receiving outpatient chemotherapy, the Khorana, PROTECHT, and ONKOTEV scores demonstrated a poor performance in predicting VTE at 6 months, highlighting the need for new tools to guide thromboprophylaxis decisions.

Systemic lupus erythematosus (SLE) is a rare and highly heterogeneous autoimmune disease in which standard treatment is based on corticosteroids and conventional or biological immunosuppressive drugs. In severe SLE patients (resistant to first- and second-line therapies), the 10-year mortality rate remains around 10-15%. Autologous anti-CD19 chimeric antigen receptor (CAR) T-cell therapy has recently demonstrated sustained remission in this subset of SLE patients, but the number of treated patients remains low. The objective of this study was to assess the clinical practices (CPs) and various challenges in recruiting severe SLE patients eligible for CAR T-cell therapy. A 1-year (February 2024 to February 2025) retrospective multicenter study was conducted across seven certified autoimmune disease reference centers. All adult SLE patients fulfilling the 2019 European Alliance of Associations for Rheumatology/American College of Rheumatology criteria were screened for disease activity and severity according to the 2024 EBMT-International Society for Cell & Gene Therapy expert consensus. Eligibility for CAR T-cell or other non-cell and gene therapy trials and reasons for non-inclusion were analyzed. Among 1844 SLE patients screened over this 1-year retrospective study: 54 (2.9%) demonstrated severe disease criteria and, three (0.16 %) were ultimately treated by CAR- T while 49 were not selected for CAR T-cell trials because of either disease remission, lack of specific autoantibody, participation in other trials, physician/patient refusal or exclusion criteria at time of enrollment. Retrospective analysis of CPs showed that very few severe SLE patients were enrolled in the CAR T-cell trial despite eligibility criteria. Streamlined referral pathways, multidisciplinary coordination and improved physician education are needed to enhance access to advanced cell and gene therapies.