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[This corrects the article DOI: 10.3389/fimmu.2026.1674235.].

Background: Bridging therapy (BT) with systemic therapy (ST), radiation therapy (RT), or combined-modality therapy (CMT) is increasingly being utilized prior to chimeric antigen receptor (CAR) T-cell therapy for large B-cell lymphoma (LBCL). We report the long-term outcomes of the patients who received commercial CAR T-cell therapy with or without BT. Methods: The patients with LBCL who underwent infusion of a commercial CD19 CAR T product were eligible. The radiation was stratified as comprehensive or focal. The efficacy outcomes and toxicity were analyzed. Results: In total, 156 patients were included and, of them, 52.5% of the patients received BT. The median progression-free survival (PFS) was 0.65 years in the BT cohort compared to 1.45 years in the non-BT cohort. The median overall survival (OS) was 3.16 years in the BT cohort and was not reached in the non-BT cohort. The patients who received comprehensive radiation (versus focal) had significantly improved PFS and OS, achieving a 1-year PFS of 100% vs. 9.1% and 1-year OS of 100% vs. 45.5%. There was no difference in the severe toxicity between any of the nonbridging or BT cohorts. Conclusions: BT did not appear to compromise outcomes with respect to response rates, disease control, survival, and toxicity. The patients with limited disease treated with RT had favorable outcomes.

The role of stereotactic body radiotherapy (SBRT), which can deliver high radiation doses to focal tumors, has greatly increased in not only early-stage hepatocellular carcinoma (HCC), but also in portal vein or inferior vena cava thrombi, thus expanding this therapy to pre-transplantation and the treatment of oligometastases from HCC in combination with immune checkpoint inhibitors (ICI). In early-stage HCC, many promising prospective results of SBRT have been reported, although SBRT is not usually indicated as a first treatment potion in localized HCC according to several guidelines. In the treatment of portal vein or inferior vena cava tumor thrombi, several reports using various dose-fraction schedules have shown relatively good response rates with low toxicities and improved survival due to the rapid advancements in systemic therapy. Although SBRT is regarded as a substitute therapy when conventional bridging therapies to transplantation, such as transarterial chemoembolization (TACE) and radiofrequency ablation (RFA), are not applicable or fail in controlling tumors, SBRT may offer advantages in patients with borderline liver function who may not tolerate TACE or RFA, according to several reports. For oligometastases, the combination of SBRT with ICI could potentially induce an abscopal effect in patients with HCC, which is expected to provide the rationale for SBRT in the treatment of oligometastatic disease in the near future.

Background and purposeThere is still much debate whether bridging-therapy [intravenous thrombolysis (IVT) prior to mechanical thrombectomy (MT)] might be beneficial compared to MT alone. We investigated the effect of IVT on size and histological composition of the clots retrieved from patients undergoing bridging-therapy or MT alone.MethodsWe collected mechanically extracted thrombi from 1000 acute ischemic stroke (AIS) patients included in RESTORE registry. Patients were grouped according to the administration (or not) of IVT before thrombectomy. Gross photos of each clot were taken and Extracted Clot Area (ECA) was measured using ImageJ software. Martius Scarlett Blue stain was used to characterize the main histological clot components [red blood cells (RBCs), fibrin (FIB), platelets/other (PTL)] and Orbit Image Analysis was used for quantification. Additionally, we calculated the area of each main component by multiplying the component percent by ECA. Chi-squared and Kruskal–Wallis tests were used for statistical analysis.Results451 patients (45%) were treated with bridging-therapy while 549 (55%) underwent MT alone. When considering only percent histological composition, we did not find any difference in RBC% (P = 0.895), FIB% (P = 0.458) and PTL% (P = 0.905). However, bridging-therapy clots were significantly smaller than MT-alone clots [32.7 (14.8–64.9) versus 36.8 (20.1–79.8) mm2, N = 1000, H1 = 7.679, P = 0.006*]. A further analysis expressing components per clot area showed that clots retrieved from bridging-therapy cases contained less RBCs [13.25 (4.29–32.06) versus 14.97 (4.93–39.80) mm2, H1 = 3.637, P = 0.056] and significantly less fibrin [9.10 (4.62–17.98) versus 10.54 (5.57–22.48) mm2, H1 = 7.920, P = 0.005*] and platelets/other [5.04 (2.26–11.32) versus 6.54 (2.94–13.79) mm2, H1 = 9.380, P = 0.002*] than MT-alone clots.ConclusionsOur results suggest that previous IVT administration significantly reduces thrombus size, proportionally releasing all the main histological components.

Bariatric surgery for patients with severe obesity (body mass index (BMI) ≥ 50kg/m 2 ) is technically challenging. Intragastric balloon (IGB) has been proposed for weight loss before bariatric surgery to reduce surgical risks but its efficacy remains unclear. We conducted a systematic review and meta-analysis of the effectiveness of IGB as bridging therapy and assess potential complications. Amongst 2419 citations, 13 studies were included. IGB resulted in a BMI reduction of 6.60 kg/m 2 (MD=6.60, 95% CI: 5.06–8.15; I 2 =72%). The total post-procedural complication rate was 8.13% (95% CI: 4.04–13.17%), with majority being balloon intolerance. Overall, IGB is effective as a bridging therapy with adequate procedural safety profile, but further study is needed to evaluate the risk reduction for bariatric surgery and long-term weight-loss outcomes. Graphical abstract

CD19-directed chimeric antigen receptor T-cell (CAR T-cell) therapy has markedly improved the prognosis of patients with relapsed or refractory large B-cell lymphoma (R/R LBCL). However, disease progression during the manufacturing period remains a major barrier to successful treatment. Bridging therapy (BT), defined as anti-lymphoma treatment administered between leukapheresis and lymphodepleting chemotherapy, serves two primary purposes: to prevent disease progression ensuring eligibility for CAR T-cell infusion, and to modulate the immune microenvironment to potentially enhance CAR T-cell efficacy or mitigate its toxicity. This review provides a comprehensive overview of current strategies and clinical evidence regarding BT in the context of CAR T-cell therapy. We systematically examine the efficacy and safety profiles of various BT strategies, including chemotherapy, targeted or immunotherapy agents, and radiotherapy. Furthermore, we summarize and compare findings from pivotal clinical trials and real-world studies, offering insights into the practical application and outcomes of BT in diverse clinical settings. Unresolved questions remain, including the optimal implementation of bispecific antibodies as BT regimens, the timing and duration of Bruton’s tyrosine kinase inhibitors administration, the safety and efficacy of reusing polatuzumab vedotin in previously exposed patients, and the standardization of radiotherapy protocols. In conclusion, the rational selection and application of BT strategies hold promise for improving the clinical outcomes of R/R LBCL patients undergoing CAR T-cell therapy.

Background The comparative efficacy of tenecteplase versus alteplase in achieving early recanalization (ER) before mechanical thrombectomy (MT) for large-vessel occlusion (LVO) remains uncertain. Methods This study was a retrospective analysis of prospectively collected data of consecutive patients with LVO underwent intravenous thrombolysis (IVT) and brain angiography between January 2022 and December 2023. ER was defined as ≥ 50% reperfusion or absence of retrievable thrombus on initial angiography. Results 146 patients received tenecteplase and 307 received alteplase. Tenecteplase shortened door-to-IVT time (33 vs. 39 min,  P  < 0.001) and door-to-puncture time (97 vs. 109 min,  P  = 0.039) compared to alteplase. Overall ER rates did not differ significantly (17.1% vs. 12.1%,  P  = 0.223). However, a significant interaction was observed between thrombolytic agent and IVT-to-puncture time ( P interaction  = 0.034): tenecteplase achieved higher ER rates when IVT-to-puncture time was < 60 min (17.2% vs. 5.0%, aOR, 4.13 [95% CI 1.24–13.74]). With IVT-to-puncture time ≥ 60 min, ER rates were similar (17.2% vs. 16.8%, aOR 0.91 [95% CI 0.43–1.91]). No ER differences were noted across occlusion sites, clot burden, NIHSS, sex, and age. At 3 months, tenecteplase reduced disability rates (mRS 0–3: 73.5% vs. 65.7%, P  = 0.041). Functional independence (mRS 0–2) was 57.4% with tenecteplase and 53.1% with alteplase ( P  = 0.301). Conclusions Real-world observations reveal tenecteplase has increased ER rates compared to alteplase within 1 h of IVT and reduced disability in LVO patients. Further randomized trials are warranted to evaluate the effect of tenecteplase rapid bridging mechanical thrombectomy.

Bridging therapy can prevent patients from disease progression while waiting for CAR-T cell preparation. Hyper-fractionated radiotherapy can achieve an effective target dose within a short period, minimize radiation damage, and may modify immune environment compared to conventional radiotherapy. This study aims to investigate the efficacy and safety of bridging hyper-fractionated radiotherapy in combination with CAR-T therapy for relapsed/refractory diffuse large B-cell lymphoma. The potential mechanisms were explored. This is a prospective pilot study. After T-cell collection, the patients underwent hyper-fractionated radiotherapy at lesion sites with 1.5 Gy twice daily for 10 days before CAR-T cell infusion. Peripheral blood immune cell subsets and quantitative serum proteomics were assessed before radiotherapy and after radiotherapy before CAR-T cell infusion. A total of 13 patients have been enrolled. The median follow-up time was 6 (3-24) months after CAR-T infusion. At 3-month follow-up, 9/13(69%) patients had CR, 1/13(8%) patient had PR, 1/13(8%) patient remained SD, and 2/13(15%) patients died of disease progression. The local recurrence rate was 1/13(8%). Seven patients have been followed up for more than 6 months, and they remain in CR. The median PFS and OS were not reached. No grade 3-4 CRS or ICANS were reported. After hyper-fractionated radiotherapy, peripheral PD1+CD8+T/T ratio significantly decreased while quantitative serum proteomics profiling showed a decrease in sCD28. Hyper-fractionated radiotherapy can rapidly control tumor progression sites without delaying the infusion time. This approach can improve the ORR and does not increase the incidence of CRS and ICANS. The mechanism may be related to the regulation of T-cell co-stimulatory molecules, which demands further exploration.

Bortezomib (Velcade), thalidomide, dexamethasone, platinum (cisplatin), adriamycin (doxorubicin), cyclophosphamide, and etoposide (VTD-PACE) are commonly used as salvage treatment for patients with relapsed/refractory multiple myeloma (RRMM). However, its outcomes in the era of monoclonal antibodies remain unclear. Therefore, this retrospective cohort study assessed the clinical outcomes of 60 patients with RRMM (median four prior treatment lines) administered VTD-PACE. The median follow-up period was 11.1 months, during which they received a median of two cycles of VTD-PACE. The overall response rate (ORR) was 66.7%; ORRs of 53.1 and 82.1% were noted in patients with ≥ 4 and ≤ 3 prior lines (P = 0.027), respectively. The median overall survival (OS) was 17 months, with a median progression-free survival (PFS) of 9.8 months. Using the 3-month time point after VTD-PACE treatment as a landmark, 54 patients were still alive. Landmark analysis was conducted for PFS and OS of patients who received or did not receive HSCT or CART after VTD-PACE treatment. Patients who underwent subsequent hematopoietic stem cell transplantation (HSCT) or chimeric antigen receptor T-cell therapy (CART) following VTD-PACE showed a trend of longer PFS and OS than those who did not undergo subsequent HSCT or CART. The median OS in patients with and without renal dysfunction was 10.7 months and 21.5 months, respectively (P = 0.0091). Therefore, VTD-PACE is useful as a bridging therapy for HSCT or CART, as a response can be expected regardless of organ damage, disease risk, or history of anti-CD38 antibody use.

Background Radiotherapy (RT) with immunochemotherapy (ICT) followed by CAR T-cell therapy may have synergistic effects due to cytoreduction and enhancing antigen spread, thereby inducing anti-cancer immune responses. The aim of this study was to analyze retrospective comparative data on the use of RT prior to anti-CD19 directed CAR T-cell therapy with a special focus on cytoreduction and RT related side effects. Methods All patients aged ≥ 18 years with relapsed/ refractory Large B-Cell-lymphoma (r/r LBCL) treated with anti-CD19 CAR T-cell therapy in our institution from 05/ 2019–08/2023 were analyzed retrospectively, with the RT therapy group comprising all patients receiving RT with or without concomitant systemic therapy. The control (CO) group was manually matched on age, prior therapy lines and remission state at lymphodepletion. Post-RT tumor volumes (TV) were calculated for 6 out of 7 patients pre-CAR T and for 1 patient post-CAR T. Primary endpoints were reduction of TV and CAR T as well as RT related side effects. Secondary endpoints included overall survival (OS) and progression free survival (PFS). Results 8 patients receiving RT within 60 days prior to CAR T-cell infusion and 8 controls were included in the final analysis. 6 out of 8 patients received concomitant bridging therapy. RT alone or in combination with concomitant systemic therapy led to a significant reduction of TV (average reduction of 68%) within the radiated field from baseline to post RT ( p  = 0.028). The combination of RT and CAR T-cell therapy was not associated with an increased rate of CAR T related side effects or complications (cytokine release syndrome p  = 0.6, immune effector cell-associated neurotoxicity p  = 0.2, corticosteroid use p  > 0.9, Tocilizumab use p  > 0.9, transfer to intensive care unit p  = 0.6). OS and PFS did not differ between the RT- and CO-group (OS p  = 0.64, PFS p  = 0.35). Conclusions Our data indicate that RT is a feasible and effective way of cytoreduction before CAR T-cell therapy, also in combination with systemic chemotherapy. Clinical trial number Not applicable.