Intravesical administration of combined hyaluronic acid (HA) and chondroitin sulfate (CS) for the treatment of female recurrent urinary tract infections: a European multicentre nested case-control study.

Published onlineJournal ArticleMulticenter StudyObservational StudyResearch Support, Non-U.S. Gov'tThis is the final version of the article. Available from BMJ Publishing Group via the DOI in this record.OBJECTIVES: To compare the clinical effectiveness of the intravesical administration of combined hyaluronic acid and chondroitin sulfate (HA+CS) versus current standard management in adult women with recurrent urinary tract infections (RUTIs). SETTING: A European Union-based multicentre, retrospective nested case-control study. PARTICIPANTS: 276 adult women treated for RUTIs starting from 2009 to 2013. INTERVENTIONS: Patients treated with either intravesical administration of HA+CS or standard of care (antimicrobial/immunoactive prophylaxis/probiotics/cranberry). PRIMARY AND SECONDARY OUTCOME MEASURES: The primary outcome was occurrence of bacteriologically confirmed recurrence within 12 months. Secondary outcomes were time to recurrence, total number of recurrences, health-related quality of life and healthcare resource consumption. Crude and adjusted results for unbalanced characteristics are presented. RESULTS: 181 patients treated with HA+CS and 95 patients treated with standard of care from 7 centres were included. The crude and adjusted ORs (95% CI) for the primary end point were 0.77 (0.46 to 1.28) and 0.51 (0.27 to 0.96), respectively. However, no evidence of improvement in terms of total number of recurrences (incidence rate ratio (95% CI), 0.99 (0.69 to 1.43)) or time to first recurrence was seen (HR (95% CI), 0.99 (0.61 to 1.61)). The benefit of intravesical HA+CS therapy improves when the number of instillations is ≥ 5. CONCLUSIONS: Our results show that bladder instillations of combined HA+CS reduce the risk of bacteriologically confirmed recurrences compared with the current standard management of RUTIs. Total incidence rates and hazard rates were instead non-significantly different between the 2 groups after adjusting for unbalanced factors. In contrast to what happens with antibiotic prophylaxis, the effectiveness of the HA+CS reinstatement therapy improves over time. TRIAL REGISTRATION NUMBER: NCT02016118.This study was funded by an unrestricted grant from the TETI Association—study group for urogenital diseases. Members of the association were involved in the data collection and revised the manuscript

Efficacy of checkpoint inhibition after CAR-T failure in aggressive B-cell lymphomas: outcomes from 15 US institutions

Checkpoint inhibitor (CPI) therapy with anti-PD-1 antibodies has been associated with mixed outcomes in small cohorts of patients with relapsed aggressive B-cell lymphomas after CAR-T failure. To define CPI therapy efficacy more definitively in this population, we retrospectively evaluated clinical outcomes in a large cohort of 96 patients with aggressive B-cell lymphomas receiving CPI therapy after CAR-T failure across 15 US academic centers. Most patients (53%) had diffuse large B-cell lymphoma, were treated with axicabtagene ciloleucel (53%), relapsed early (≤180 days) after CAR-T (83%), and received pembrolizumab (49%) or nivolumab (43%). CPI therapy was associated with an overall response rate of 19% and a complete response rate of 10%. Median duration of response was 221 days. Median progression-free survival (PFS) and overall survival (OS) were 54 and 159 days, respectively. Outcomes to CPI therapy were significantly improved in patients with primary mediastinal B-cell lymphoma. PFS (128 vs 51 days) and OS (387 vs 131 days) were significantly longer in patients with late (>180 days) vs early (≤180 days) relapse after CAR-T. Grade ≥3 adverse events occurred in 19% of patients treated with CPI. Most patients (83%) died, commonly because of progressive disease. Only 5% had durable responses to CPI therapy. In the largest cohort of patients with aggressive B-cell lymphoma treated with CPI therapy after CAR-T relapse, our results reveal poor outcomes, particularly among those relapsing early after CAR-T. In conclusion, CPI therapy is not an effective salvage strategy for most patients after CAR-T, where alternative approaches are needed to improve post-CAR-T outcomes

Intravesical treatment with highly-concentrated hyaluronic acid and chondroitin sulphate in patients with recurrent urinary tract infections: Results from a multicentre survey.

INTRODUCTION: We assess the effectiveness of intravesical instillation of hyaluronic acid (HA) and chondroitin sulphate (CS) as a non-antibiotic treatment option for prophylaxis of recurrent urinary tract infections (UTIs) in female patients. METHODS: This was a retrospective cohort study involving 7 European institutions. We included patients with recurrent UTIs who received intravesical instillations of Ialuril (IBSA International) (50 mL HA 1.6% and CS 2% solution) between January 2010 and March 2012. Medication schedule, length of follow-up, recurrence infection time, number of UTIs/patients/year, patient quality of life, subjective symptoms score, and treatment-emergent side effects were recorded and analyzed. RESULTS: In total, 157 women (mean age: 54.2 ± 4.1 years) were included in the analysis. All patients had at least 12 months follow-up. After 4 weekly and 5 monthly HA-CS bladder instillations, UTI episodes decreased from 4.13 ± 1.14 to 0.44 ± 0.50 (p = 0.01) at 12 months, while recurrent UTI time prolonged from 94.8 ± 25.1 days to 178.4 ± 37.3 days (p = 0.01) at 12 months. An improvement in symptoms and quality of life was achieved. A medium-depth pain after medication instillation was the most reported side effect. Regression model analysis showed significant risk factors in developing new UTI episodes: being more than 50 years old and having more than 4 UTI episodes per year (OR 3.41; CI 95%; 1.51-7.71, p = 0.003 and OR 3.31; CI 95% 1.51-7.22; p = 0.003, respectively). Retrospective design and lack of a control group represent two main limitations of the study. CONCLUSIONS: Restoring glycosaminoglycans bladder layer therapy is a promising non-antibiotic therapy to prevent recurrent UTIsIntroduction: We assess the effectiveness of intravesical instillation of hyaluronic acid (HA) and chondroitin sulphate (CS) as a non-antibiotic treatment option for prophylaxis of recurrent urinary tract infections (UTIs) in female patients.Methods: This was a retrospective cohort study involving 7 European institutions. We included patients with recurrent UTIs who received intravesical instillations of Ialuril (IBSA International) (50 mL HA 1.6% and CS 2% solution) between January 2010 and March 2012. Medication schedule, length of follow-up, recurrence infection time, number of UTIs/patients/year, patient quality of life, subjective symptoms score, and treatment-emergent side effects were recorded and analyzed.Results: In total, 157 women (mean age: 54.2 ± 4.1 years) were included in the analysis. All patients had at least 12 months followup. After 4 weekly and 5 monthly HA-CS bladder instillations, UTI episodes decreased from 4.13 ± 1.14 to 0.44 ± 0.50 (p = 0.01) at 12 months, while recurrent UTI time prolonged from 94.8 ± 25.1 days to 178.4 ± 37.3 days (p = 0.01) at 12 months. An improvement in symptoms and quality of life was achieved. A medium-depth pain after medication instillation was the most reported side effect. Regression model analysis showed significant risk factors in developing new UTI episodes: being more than 50 years old and having more than 4 UTI episodes per year (OR 3.41; CI 95%; 1.51-7.71, p = 0.003 and OR 3.31; CI 95% 1.51-7.22; p = 0.003, respectively). Retrospective design and lack of a control group represent two main limitations of the study.Conclusions: Restoring glycosaminoglycans bladder layer therapy is a promising non-antibiotic therapy to prevent recurrent UTIs

Efficacy of checkpoint inhibition after CAR-T failure in aggressive B-cell lymphomas: Outcomes from 15 U.S. institutions

Checkpoint inhibitor (CPI) therapy with anti-PD-1 antibodies has been associated with mixed outcomes in small cohorts of aggressive B-cell lymphoma patients following CAR T-cell therapy failure. To more definitively define CPI therapy efficacy in this population, we retrospectively evaluated clinical outcomes in a large cohort of 96 patients with aggressive B-cell lymphomas receiving CPI therapy after CAR-T failure across 15 U.S. academic centers. Most patients (53%) had DLBCL, were treated with axicabtagene ciloleucel (53%), relapsed early (≤180 days) after CAR-T (83%), and received pembrolizumab (49%) or nivolumab (43%). CPI therapy was associated with an overall response rate of 19% and a complete response rate of 10%. Median duration of response was 221 days. Median progression-free survival (PFS) and overall survival (OS) were 54 and 159 days, respectively. Outcomes to CPI therapy were significantly improved in patients with primary mediastinal B-cell lymphoma. PFS (128 versus 51 days) and OS (387 versus 131 days) were significantly longer in patients with late (>180 days) versus early (≤180 days) relapse after CAR-T. Grade ≥3 adverse events occurred in 19% of CPI-treated patients. Most patients (83%) died, commonly due to progressive disease. Only 5% had durable responses to CPI therapy. In the largest cohort of aggressive B-cell lymphoma patients treated with CPI therapy after CAR-T relapse, our results reveal poor outcomes, particularly among those relapsing early after CAR-T. In conclusion, CPI therapy is not an effective salvage strategy for most patients after CAR-T, where alternative approaches are needed to improve post-CAR-T outcomes

Allogeneic transplantation after PD-1 blockade for classic Hodgkin lymphoma

Anti-PD-1 monoclonal antibodies yield high response rates in patients with relapsed/refractory classic Hodgkin lymphoma (cHL), but most patients will eventually progress. Allogeneic hematopoietic cell transplantation (alloHCT) after PD-1 blockade may be associated with increased toxicity, raising challenging questions about the role, timing, and optimal method of transplantation in this setting. To address these questions, we assembled a retrospective cohort of 209 cHL patients who underwent alloHCT after PD-1 blockade. With a median follow-up among survivors of 24 months, the 2-year cumulative incidences (CIs) of non-relapse mortality and relapse were 14 and 18%, respectively; the 2-year graft-versus-host disease (GVHD) and relapse-free survival (GRFS), progression-free survival (PFS), and overall survival were 47%, 69%, and 82%, respectively. The 180-day CI of grade 3–4 acute GVHD was 15%, while the 2-year CI of chronic GVHD was 34%. In multivariable analyses, a longer interval from PD-1 to alloHCT was associated with less frequent severe acute GVHD, while additional treatment between PD-1 and alloHCT was associated with a higher risk of relapse. Notably, post-transplant cyclophosphamide (PTCy)-based GVHD prophylaxis was associated with significant improvements in PFS and GRFS. While awaiting prospective clinical trials, PTCy-based GVHD prophylaxis may be considered the optimal transplantation strategy for this patient population