Long-term Efficacy In Patients Research Articles

Implications of β-Arrestin biased signaling by angiotensin II type 1 receptor for cardiovascular drug discovery and therapeutics

Angiotensin II receptors, Type 1 (AT1R) and Type 2 (AT2R) are 7TM receptors that play critical roles in both the physiological and pathophysiological regulation of the cardiovascular system. While AT1R blockers (ARBs) have proven beneficial in managing cardiac, vascular and renal maladies they cannot completely halt and reverse the progression of pathologies. Numerous experimental and animal studies have demonstrated that β-arrestin biased AT1R-ligands (such as SII-AngII, S1I8, TRV023, and TRV027) offer cardiovascular benefits by blocking the G protein signaling while retaining the β-arrestin signaling. However, these ligands failed to show improvement in heart-failure outcome over the placebo in a phase IIb clinical trial. One major limitation of current β-arrestin biased AT1R-ligands is that they are peptides with short half-lives, limiting their long-term efficacy in patients. Additionally, β-arrestin biased AT1R-ligand peptides, may inadvertently block AT2R, a promiscuous receptor, potentially negating its beneficial effects in post-myocardial infarction (MI) patients. Therefore, developing a small molecule β-arrestin biased AT1R-ligand with a longer half-life and specificity to AT1R could be more effective in treating heart failure. This approach has the potential to revolutionize the treatment of cardiovascular diseases by offering more sustained and targeted therapeutic effects.

Effect of acupuncture on quality of life in patients with chronic prostatitis/chronic pelvic pain syndrome: a randomized controlled trial.

To observe the effect and safety of acupuncture on quality of life, pain, and prostate symptoms in patients with chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS). Seventy patients with CP/CPPS were randomly divided into an acupuncture group (35 cases, 1 case was eliminated) and a sham acupuncture group (35 cases, 3 cases dropped out). The patients in the acupuncture group were treated with routine acupuncture at bilateral Zhongliao (BL 33), Huiyang (BL 35), Shenshu (BL 23) and Sanyinjiao (SP 6), while the patients in the sham acupuncture group were treated with shallow needling at non-meridian and non-acupoint points beside bilateral Zhongliao (BL 33), Huiyang (BL 35), Shenshu (BL 23) and Sanyinjiao (SP 6),without manipulation to induce arrival of qi (deqi). Both groups retained the needles for 30 min, with one session every other day, three times a week, for a total of 8 weeks (24 sessions). Before and after treatment, and at the follow-up of 24 weeks after treatment completion, the scores of MOS 36-item short-form health survey (SF-36, including 8 dimensions of physical function [PF], role physical function [RP], bodily pain [BP], general health status [GH], vitality [VT], social function [SF], role emotional [RE], and mental health [MH], which can be summarized as physical component summary [PCS] and mental component summary [MCS]), pelvic pain visual analogue scale (VAS), National Institutes of Health chronic prostatitis symptom index (NIH-CPSI), and international prostate symptom score (IPSS) were evaluated, and safety of both groups was assessed. After treatment and at the follow-up, the scores of each dimension and PCS, MCS scores of SF-36 in the acupuncture group were higher than those before treatment (P<0.05, P<0.01); compared before treatment, the RP, BP, and SF scores and PCS score in the sham acupuncture group were increased after treatment (P<0.05, P<0.01). After treatment, the acupuncture group had higher scores in RP, BP, GH, MH and PCS, MCS than those in the sham acupuncture group (P<0.05, P<0.01); at the follow-up, except for PF and RE dimensions, the scores in each dimension and PCS, MCS scores in the acupuncture group were higher than those in the sham acupuncture group (P<0.05, P<0.01). After treatment and at the follow-up, pelvic pain VAS, NIH-CPSI, IPSS scores in the acupuncture group were lower than those before treatment (P<0.01); in the sham acupuncture group, pelvic pain VAS, NIH-CPSI scores were lower after treatment, and NIH-CPSI score at the follow-up was lower compared with those before treatment (P<0.01). After treatment and at the follow-up, pelvic pain VAS, NIH-CPSI, IPSS scores in the acupuncture group were lower than those in the sham acupuncture group (P<0.01, P<0.05). No significant adverse reactions were observed in both groups, and the incidence rates of adverse reactions had no significant difference (P>0.05). Acupuncture could effectively improve the quality of life, reduce pain levels, alleviate prostate symptoms, and shows favorable long-term efficacy in patients with CP/CPPS.

Prognostic value of body composition on survival outcomes in melanoma patients receiving immunotherapy.

The influence of body composition on the effectiveness of immune checkpoint inhibitors (ICIs) in patients with melanoma is still uncertain in clinical practice. Therefore, the objective of this study was to examine the potential association between body composition and clinical outcomes in patients with melanoma undergoing ICIs treatment. A systematic literature search was performed across several databases, including PubMed, Embase, Cochrane Library and Google Scholar, to gather relevant studies. The primary outcomes of interest were overall survival (OS) and progression-free survival (PFS), assessed by hazard ratios (HR). Secondary outcomes, such as adverse events (AE), were evaluated using odds ratios (OR). This meta-analysis comprised ten articles involving a total of 1,283 patients. Systemic analysis of all collected evidence revealed that body composition, including low skeletal muscle index (SMI) (OS: HR = 1.66, 95% CI = 1.13-2.43, p = 0.010; PFS: HR = 1.28, 95% CI = 1.06-1.55, p = 0.009), high subcutaneous adipose tissue density (SMD) (OS: HR = 1.93, 95% CI = 1.09-3.44, p = 0.025; PFS: HR = 1.31, 95% CI = 1.06-1.63, p = 0.012), and sarcopenia (OS: HR = 1.25, 95% CI = 1.03-1.51, p = 0.022; PFS: HR = 1.25, 95% CI = 1.03-1.51, p = 0.022), were significantly associated with OS and PFS in melanoma patients treated with ICIs. However, these markers did not show a significant association with treatment-related adverse events. Interestingly, no significant correlation was found between visceral fat index (VFI) (OS: HR = 0.71, 95% CI = 0.29-1.76, p = 0.462; PFS: HR = 0.98, 95% CI = 0.93-1.02, p = 0.274) and OS or PFS in melanoma patients under ICIs treatment. Body composition was found to be associated with decreased treatment response and lower long-term efficacy in patients with melanoma undergoing immune checkpoint inhibitor (ICI) therapy. However, it is important to note that body composition did not appear to contribute to increased incidence of adverse events in these patients.

Maintenance of Response to Risankizumab in Patients With Psoriatic Arthritis: A 3-year Analysis of the KEEPsAKE 1 and 2 Trials

Introduction: Risankizumab, a humanized immunoglobulin G1 monoclonal antibody, specifically inhibits the p19 subunit of human interleukin 23 and is approved for treatment of active psoriatic arthritis (PsA) in adults. This post hoc analysis evaluated the long-term maintenance of clinical response through ~3 years of risankizumab treatment using data from 2 ongoing phase 3 trials, KEEPsAKE 1 and KEEPsAKE 2.&#x0D; Methods: Eligible patients had active PsA with inadequate response or intolerance to ≥1 conventional synthetic disease modifying antirheumatic drugs (KEEPsAKE 1 [NCT03675308]; KEEPsAKE 2 [NCT03671148]) and/or inadequate response or intolerance to 1–2 biologic therapies (KEEPsAKE 2 only). Patients received double-blinded risankizumab 150 mg or placebo at weeks 0, 4, and 16 and open-label risankizumab 150 mg every 12 weeks thereafter. This analysis includes patients who received continuous risankizumab through both treatment periods. Assessments included improvement of ≥20%/50%/70% in PsA symptoms using American College of Rheumatology criteria (ACR20/50/70), achievement of minimal disease activity (MDA), reduction of ≥90% in Psoriasis Area and Severity Index (PASI 90; in patients with ≥3% body surface area affected by psoriasis at baseline), and clinically meaningful reduction in pain (≥10 mm on a visual analog scale [VAS]). Maintenance of response analyses were based on patients who were responders at weeks 24 or 52 for each endpoint. Nonresponder imputation incorporating multiple imputation (NRI-MI) for missing data due to COVID-19 or geopolitical conflict was used. As-observed data were also reported.&#x0D; Results: Among patients receiving continuous risankizumab, ACR20 was achieved at week 24 in 267/454 (KEEPsAKE 1, 58.8%) and 111/208 (KEEPsAKE 2, 53.4%) patients (as observed). Maintenance of response in week 24 ACR20 responders (NRI-MI) was achieved for ACR20 by most patients at week 52 (KEEPsAKE 1, 89.1%; KEEPsAKE 2, 77.0 %) and week 148 (KEEPsAKE 1, 74.7%; KEEPsAKE 2; 68.5%). Similar patterns of maintenance of response were observed for ACR50 and ACR70. Week 24 responders also maintained MDA at weeks 52 (KEEPsAKE 1, 82.2%; KEEPsAKE 2, 66.7%) and 148 (KEEPsAKE 1, 77.1%; KEEPsAKE 2, 71.9%). The PASI 90 response was maintained at weeks 52 (KEEPsAKE 1, 86.6%; KEEPsAKE 2, 88.4%) and 148 (KEEPsAKE 1, 76.3%; KEEPsAKE 2, 81.2%). Week 24 responders maintained clinically meaningful reductions in pain VAS at weeks 52 (KEEPsAKE 1, 83.9%; KEEPsAKE 2, 74.4%) and 148 (KEEPsAKE 1, 75.0%; KEEPsAKE 2, 72.0%). Comparable maintenance of response was recorded at week 148 for each endpoint among week 52 responders (NRI-MI).&#x0D; Conclusion: Risankizumab demonstrated durable long-term efficacy in patients with active PsA. A high proportion of patients receiving continuous risankizumab treatment in KEEPsAKE 1 and KEEPsAKE 2 achieved responses in ACR20/50/70, MDA, PASI 90, or pain VAS at weeks 24 or 52 and maintained responses through week 148.

43827 Deucravacitinib Long-term Efficacy in Patients Originally Randomized to Placebo: 2-Year Results From the POETYK PSO Program

43827 Deucravacitinib Long-term Efficacy in Patients Originally Randomized to Placebo: 2-Year Results From the POETYK PSO Program

Surgeon experience with insurance barriers to offering gastric bypass as an evidence-based operation for pathologic GERD.

Obesity is an increasingly prevalent public health problem often associated with poorly controlled gastroesophageal reflux disease. Fundoplication has been shown to have limited long-term efficacy in patients with morbid obesity and does not address additional weight-related co-morbidities. Roux-en-Y gastric bypass (RYGB) is the gold standard operation for durable resolution of GERD in patients with obesity, and is also used as a salvage operation for GERD after prior foregut surgery. Surgeons report access to RYGB as surgical treatment for GERD is often limited by RYGB-specific benefit exclusions embedded within insurance policies, but the magnitude and scope of this problem is unknown. A 9-item survey evaluating surgeon practice and experience with insurance coverage for RYGB for GERD was developed and piloted by a SAGES Foregut Taskforce working group. This survey was then administered to surgeon members of the SAGES Foregut Taskforce and to surgeons participating in the SAGES Bariatrics and/or Foregut Facebook groups. 187 surgeons completed the survey. 89% reported using the RYGB as an anti-reflux procedure. 44% and 26% used a BMI of 35kg/m2 and 30kg/m2 respectively ascutoff for the RYGB. 89% viewedRYGB as the procedure of choice for GERD after bariatric surgery. 69% reported using RYGB to address recurrent reflux secondary tofailed fundoplication. 74% of responders experienced trouble with insurance coverage at least half the time RYGB was offered for GERD, and 8% reported they were never able to get approval for RYGBfor GERD indications in their patient populations. For many patients,GERD and obesity are related diseases that are best addressed with RYGB. However, insurance coverage for RYGB for GERD is often limited by policies which run contrary to evidence-based medicine. Advocacy is critical to improve access to appropriate surgical care for GERD in patients with obesity.

Dupilumab sustains efficacy in patients with moderate-to-severe type 2 asthma regardless of ICS dose.

Dupilumab, a human monoclonal antibody, blocks the shared receptor component for interleukins-4/13, key and central drivers of type 2 inflammation. The TRAVERSE (NCT02134028) open-label extension study demonstrated the long-term safety and efficacy of dupilumab in patients ≥12 years who completed a previous dupilumab asthma study. The safety profile was consistent with that observed in the parent studies. Here, we assess whether dupilumab sustains long-term efficacy in patients regardless of inhaled corticosteroid (ICS) dose at parent study baseline (PSBL). Patients from phase 2b (NCT01854047) or phase 3 (QUEST; NCT02414854) studies receiving high- or medium-dose ICS at PSBL and enrolled in TRAVERSE were included. We analyzed unadjusted annualized severe exacerbation rates, change from PSBL in pre-bronchodilator (BD) forced expiratory volume in 1 second (FEV1 ), 5-item asthma control questionnaire, and type 2 biomarkers in patients with type 2 asthma at baseline (blood eosinophils ≥150 cells/μL or fractional exhaled nitric oxide [FeNO] ≥25 ppb), and subgroups defined by baseline blood eosinophils or FeNO. Of patients with type 2 asthma (n = 1666), 891 (53.5%) were receiving high-dose ICS at PSBL. In this subgroup, unadjusted exacerbation rates for dupilumab versus placebo were 0.517 versus 1.883 (phase 2b) and 0.571 versus 1.300 (QUEST) over the parent study (52 weeks) and remained low throughout TRAVERSE (0.313-0.494). Improvements in pre-BD FEV1 were sustained throughout TRAVERSE. Similar clinical efficacy was observed among patients receiving medium-dose ICS at PSBL and biomarker subgroups. Dupilumab showed sustained efficacy for up to 3 years in patients with uncontrolled, moderate-to-severe type 2 asthma on high- or medium-dose ICS.

Long-term efficacy in patients with relapsed/refractory diffuse large B-cell lymphoma achieving a complete response with pixantrone.

The prognosis of diffuse large B-cell lymphoma (DLBCL) patients with refractory or multiply relapsed (R/R) disease is disappointing. Pixantrone is currently approved as third or fourth line regimen, with encouraging results, even if long-term follow-up data are limited. In this post-hoc analysis of our observational study, we retrospectively investigated disease outcome and clinical characteristics of 16 R/R DLBCL patients who achieved a complete response with pixantrone. Pixantrone was administered as third or fourth line in 12/16 (75%) and 4/16 (25%) cases. After a median follow-up of 24 months, 14/16 patients (87.5%) were alive (causes of death were progressive disease and secondary acute myeloid leukemia, one case each). Median progression-free survival was 23.8 months, median duration of response was 17.8 months and median overall survival (OS) was not reached (2-years OS was 84%). A significant proportion of patients achieved a long-lasting response >12 months (7/16 cases). Response to prior therapy did not influence long-term remission after pixantrone. In this real-life experience, pixantrone demonstrated long-term efficacy in a cohort of R/R DLBCL cases who had previously received at least two prior regimens; many of whom had characteristics associated with poor prognosis.

Combining chemotherapy and tislelizumab with preoperative split-course hypofraction radiotherapy for locally advanced rectal cancer: study protocol of a prospective, single-arm, phase II trial

IntroductionShort-course radiotherapy (SCRT) with systemic therapy has the potential to further improve the long-term efficacy in patients with locally advanced rectal cancer (LARC). To maximise the benefits of neoadjuvant therapy...

Dupilumab long-term efficacy in patients with non–OCS–dependent asthma with and without evidence of allergic asthma

Objective The open-label extension TRAVERSE study (NCT02134028) assessed dupilumab long-term safety and efficacy in patients who completed Phase 2/3 dupilumab asthma studies. This post hoc analysis evaluated long-term efficacy in type 2 patients with and without evidence of allergic asthma who enrolled in TRAVERSE from Phase 3 QUEST (NCT02414854) and Phase 2b (NCT01854047) studies. Non–type 2 patients with evidence of allergic asthma were also assessed. Methods Unadjusted annualized exacerbation rates during parent study and TRAVERSE treatment period, and changes from parent study baseline in pre-bronchodilator forced expiratory volume in 1 s (FEV1) and in 5-item Asthma Control Questionnaire (ACQ-5) scores were assessed in patients from QUEST and Phase 2b; change from parent study baseline in total IgE level was assessed in patients enrolled from Phase 2b. Results 2062 patients from Phase 2b and QUEST enrolled in TRAVERSE. Of these, 969 were type 2 with evidence of allergic asthma; 710 were type 2 without evidence of allergic asthma; and 194 were non–type 2 with evidence of allergic asthma at parent study baseline. In these populations, reductions in exacerbation rates observed during parent studies were sustained during TRAVERSE. Type 2 patients who switched from placebo arm to dupilumab in TRAVERSE experienced similar reductions in severe exacerbation rates, and improvements in lung function and asthma control to those patients who already received dupilumab during the parent study. Conclusion Dupilumab efficacy was sustained for up to 3 years in patients with uncontrolled, moderate-to-severe type 2 inflammatory asthma, with or without evidence of allergic asthma. ClinicalTrials.gov identifier: NCT02134028

P-MCP treatment in non-metastatic biochemically relapsed prostate cancer (BRPC-M0): Final long-term results of a prospective phase II study.

162 Background: 30% of patients with localized PC will have a biochemical relapse post local therapy. Their optimal treatment remains elusive. While androgen deprivation therapy is effective in reducing PSA level, its long-term benefit remains undefined, and it is toxic. Thus, evaluation of new nontoxic compounds in these patients is warranted. PectaSol-C modified citrus pectin (P-MCP) is an inhibitor of galectin-3 protein, which is involved in prostate cancer pathogenesis. We herein report the final long-term results of a multi-center phase 2 study of P-MCP treatment in BRPC-M0. Methods: Patients with BRPC-M0 were enrolled and treated with P-MCP, 4.8 grams X 3/day, for 6 months (first phase of trial). Patients without PSA progression and/or with improvement of PSA doubling time (PSADT), and with negative scans, were treated for an additional 12 months (second phase of trial). Results: 59 patients were initially enrolled. After initial 6 months of therapy, 46 patients (78%) without disease progression entered the second phase of additional 12 months therapy. Among them, 7 patients withdrew consent and chose to continue therapy out of pocket. Of the remaining 39 patients, after another year of therapy (total of 18 months), 85% (n=33) had an overall long-term response, with a decreased/stable PSA (62 %, n=24), and improvement of PSADT (90 %, n=35), and with negative scans. No patient had grade 3/4 toxicity. Conclusions: P-MCP may have a durable long-term efficacy in patients with BRPC-M0. Clinical trial information: NCT01681823 .

Total knee arthroplasty exhibits satisfactory long-term clinical efficacy in the treatment of hemophilia patients with stiff knees.

This study aimed to (1) determine the long-term clinical efficacy of total knee arthroplasty (TKA) in the treatment of hemophilia patients with stiff knessknees, (2) assess the 5- and 10-year prosthesis survival in hemophilia, and (3) determine whether the severity of preoperative stiffness would affect postoperative clinical outcomes and complication rates. The clinical data of 71 patients (78 knees) with hemophilia and concomitant knee stiffness who had undergone TKA between September 2007 and June 2018 were retrospectively analyzed. All patients were male, their mean age at the time of surgery was 38.4. ± 7.9 years (range: 21-63 years), and the mean follow-up time was 8.7 years. To determine the effect of stiffness severity on clinical outcomes, the participants were categorized into two groups: severe [preoperative range of motion (ROM): <50°, 34 knees] and moderate (preoperative ROM: 50-90°, 44 knees). At preoperative and final follow-up, patients' post-TKA clinical and radiological outcomes, quality of life, complications, and long-term survival were assessed. Flexion contracture improved from 23.2 ± 10.8° before surgery to 5.9 ± 7.5° upon final follow-up, the Knee Society Score (KSS) increased from 31.4 ± 12.4 to 74.9 ± 11.5, and the KSS functional score increased from 37.6 ± 9.3 to 81.4 ± 12.8. The mean ROM improved from 54.6 ± 32.6° preoperatively to 80.9 ± 34.5° postoperatively. The 36-Item Short Form Survey physical and mental scores also improved significantly. All these differences were statistically significant before and after surgery (P < 0.001). The following postoperative complications occurred in 10 knees (12.8%): hemarthrosis (n = 3), stiffness (n = 4), superficial infection (n = 1), skin necrosis (n = 1), and periprosthetic infection (n = 2), and revision TKA was performed on two knees. The 5- and 10-year survival rates of the prostheses were 98.5% and 93.7%, respectively. The mean ROM in the severe group increased from 30.7 ± 18.7° preoperatively to 70.5 ± 28.3° postoperatively (p < 0.001). The mean flexion contracture decreased from 27.3 ± 10.8° to 6.4 ± 12.0° (p < 0.001). The mean KSS improved from 27.0 ± 7.8 to 68.3 ± 9.6 (p < 0.001). The mean ROM in the moderate group improved from 84.3 ± 22.7 to 92.9 ± 28.8 (p < 0.001), while the mean flexion contracture decreased from 12.8 ± 11.0° to 4.8 ± 5.0° (p < 0.001) and the mean KSS improved from 41.3 ± 11.5 to 81.3 ± 12.2 (p < 0.001). The severe group had worse postoperative ROM and functional scores than the moderate group. Furthermore, the severe group used varus-valgus constrained or hinged prostheses more frequently (52.8% vs. 18.1%) and had more complications (18.9% vs. 9.0%) than the moderate group. TKA exhibits satisfactory long-term efficacy in patients with hemophilic knee joint disease involving preoperative stiffness, thus potentially providing a significant improvement in function and reducing pain. Furthermore, severely stiff knee joints have worse clinical outcomes and more complications than moderately stiff knee joints.

Sequential Administration of Selinexor then CD19 CAR-T Cells Exhibits Enhanced Efficacy in a Mouse Model of Human Non-Hodgkin's Lymphoma

Novel therapeutic approaches are urgently needed for many patients with Non-Hodgkin's Lymphoma (NHL). Approximately 30% of patients die within 5 years of diagnosis and many more relapse. Chimeric Antigen Receptor T cells (CAR-T) directed toward NHL antigens (e.g. CD19) are a promising new class of therapeutics for some patients with relapsed/refractory NHL, though a high percentage of patients (~50%) still fail to enter remission or relapse within one year of CD19 CAR-T therapy. Another approved therapeutic for treatment of a subtype of NHL patients is the nuclear export inhibitor, selinexor. Selinexor binds to exportin 1 and exhibits anti-tumor activity by impairing nuclear export of proteins including oncogenes and tumor suppressor proteins. As both CD19 CAR-T cells and selinexor exhibit activity against lymphoma cells, but suboptimal long term efficacy in patients, we assessed the combination of both treatments in a mouse model of NHL. The combinatorial efficacy was assessed using a circulating model of human NHL whereby RAJI-luciferase cells were intravenously injected into immunocompromised mice. Initial studies initiated treatment 7 days post tumor cell injection. Mice (n=5 NSG mice per cohort) were treated with selinexor alone (10mg/kg gavage 2x week) for study duration, CD19 CAR-T cells alone (single injection of 2.5x106 million cells) or a concurrent combination. Mice were imaged weekly for bioluminescence to monitor tumor progression. While CD19 CAR-T cells alone led to inhibition of tumor growth, there was no further enhancement in efficacy with the addition of concurrent treatment with selinexor (Figure 1A). Interestingly, when selinexor instead was administered only prior to CAR-T cell injection (10mg/kg gavage Day 1 and Day 3 post tumor cell injection followed by CAR-T injection Day 7 post tumor cell injection), there was a significant reduction in tumor burden in the combination group (Figure 1B). These results suggest that the tumor cells become sensitized to CD19 CAR-T mediated cell killing from selinexor administration. As both agents are FDA approved for certain NHL patients, this therapeutic strategy has high clinical relevance. Figure 1View largeDownload PPTFigure 1View largeDownload PPT Close modal

LONG-TERM DUPILUMAB REDUCES EXACERBATIONS AND IMPROVES LUNG FUNCTION IN TYPE 2 PATIENTS WITH/WITHOUT ALLERGIC

<h3>Introduction</h3> TRAVERSE (NCT02134028) assessed dupilumab long-term safety and efficacy in patients ≥12 years who previously completed a dupilumab asthma study. Safety was consistent with the known dupilumab safety profile. This analysis of TRAVERSE evaluated dupilumab long-term efficacy in patients who previously participated in QUEST (NCT02414854) and had type 2 asthma (blood eosinophils ≥150cells/µL or fractional exhaled nitric oxide [FeNO] ≥20ppb) with or without an allergic phenotype (serum total IgE ≥30IU/mL and ≥1 perennial aeroallergen-specific IgE ≥0.35kU/L) at parent study baseline and history of ≥2 exacerbations in the year prior to QUEST. <h3>Methods</h3> In TRAVERSE, patients received dupilumab 300mg q2w for up to 96 weeks (dupilumab/dupilumab and placebo/dupilumab groups). Unadjusted annualized severe asthma exacerbation rate (AER) and change from QUEST baseline FEV₁ were assessed. <h3>Results</h3> In Year 1 of treatment (QUEST), dupilumab vs placebo reduced AER to 0.578/1.490 and 0.470/1.476 in patients with and without an allergic phenotype, respectively. In Year 2 (TRAVERSE Weeks 0–48), AER was further reduced to 0.474/0.591 and 0.320/0.295 in dupilumab/dupilumab- vs placebo/dupilumab-treated patients with and without an allergic phenotype, respectively; in Year 3 (TRAVERSE Weeks 48–96), AER was 0.353/0.203 and 0.214/0.268, respectively. Dupilumab sustained FEV₁ improvements in the dupilumab/dupilumab group and rapidly improved lung function in the placebo/dupilumab group after initiating dupilumab in TRAVERSE (<b>Figure</b>). <h3>Conclusions</h3> Dupilumab sustained reductions in exacerbations and improvements in FEV₁ for up to 3 years in patients with uncontrolled, moderate-to-severe type 2 asthma with a history of ≥2 exacerbations prior to study start, regardless of evidence of allergic asthma.

CAR density influences antitumoral efficacy of BCMA CAR T cells and correlates with clinical outcome.

Identification of new markers associated with long-term efficacy in patients treated with CAR T cells is a current medical need, particularly in diseases such as multiple myeloma. In this study, we address the impact of CAR density on the functionality of BCMA CAR T cells. Functional and transcriptional studies demonstrate that CAR T cells with high expression of the CAR construct show an increased tonic signaling with up-regulation of exhaustion markers and increased in vitro cytotoxicity but a decrease in in vivo BM infiltration. Characterization of gene regulatory networks using scRNA-seq identified regulons associated to activation and exhaustion up-regulated in CARHigh T cells, providing mechanistic insights behind differential functionality of these cells. Last, we demonstrate that patients treated with CAR T cell products enriched in CARHigh T cells show a significantly worse clinical response in several hematological malignancies. In summary, our work demonstrates that CAR density plays an important role in CAR T activity with notable impact on clinical response.

Evaluate Short-Term Outcomes of abciximab in ST-Segment Elevation Myocardial Infarction Patients Undergoing Percutaneous Coronary Intervention: A Meta-Analysis of Randomized Clinical Trials.

Objectives This meta-analysis was to verify the short-time efficacy and safety of abciximab in patients with ST-segment elevation myocardial infarction (STEMI) undergoing percutaneous coronary intervention (PCI). Background Abciximab has long-term efficacy in patients with STEMI undergoing PCI, but the short-term efficacy is still controversial. Methods We conducted a systematic review and meta-analysis compared with or without abciximab in patients with STEMI undergoing PCI. The relevant randomized controlled trials were included by searching PubMed, EMBASE, Cochrane Library, and Web of Science databases and other sources. The relative risk (RR) and 95% confidence intervals (CI) of outcomes were calculated by the fixed-effects model. Results Ten randomized controlled trials with 5008 patients met inclusion criteria. There were no significant differences in risk of all-cause death at 30-day (RR 0.79, CI 0.55–1.12, P=0.18), major bleeding (1.37, 0.93–2.03, P=0.11), and transfusion (1.23, 0.94–1.61, P=0.13) between the two groups. However, there were significant differences in risk of all-cause death at 6 months (0.57, 0.36–0.90, P=0.02), recurrent myocardial infarction (0.55, 0.33–0.92, P=0.02), repeat revascularization (0.58, 0.43–0.78, P=0.0004), final TIMI flow <3 (0.77, 0.62–0.96, P=0.02), minor bleeding (1.29, 1.02–1.63, P=0.04), and thrombocytopenia (2.04, 1.40–2.97, P=0.0002). Conclusions The application of abciximab can lead to a lower risk of reinfarction, revascularization, and all-cause death at 6 months, but a higher risk of minor bleeding, and thrombocytopenia.

MP40-08 NOVEL ENDOSCOPIC MANAGEMENT FOR LOCALIZED UPPER URINARY TRACT CARCINOMA USING A PHOTODYNAMIC DIAGNOSIS-GUIDED DUAL LASER ABLATION TECHNIQUE: 3-YEAR FOLLOW-UP RESULTS

You have accessJournal of UrologyCME1 May 2022MP40-08 NOVEL ENDOSCOPIC MANAGEMENT FOR LOCALIZED UPPER URINARY TRACT CARCINOMA USING A PHOTODYNAMIC DIAGNOSIS-GUIDED DUAL LASER ABLATION TECHNIQUE: 3-YEAR FOLLOW-UP RESULTS Takashi Yoshida, Tadashi Matsuda, Chisato Ohe, and Hidefumi Kinoshita Takashi YoshidaTakashi Yoshida More articles by this author , Tadashi MatsudaTadashi Matsuda More articles by this author , Chisato OheChisato Ohe More articles by this author , and Hidefumi KinoshitaHidefumi Kinoshita More articles by this author View All Author Informationhttps://doi.org/10.1097/JU.0000000000002600.08AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: Radical nephroureterectomy (RNU) is the gold standard treatment for localized upper tract urothelial carcinoma (UTUC); however, ureteroscopic surgery (URS) has become a more common treatment option for low-risk cases (<2 cm, low grade, and low stage) or imperative cases (solitary kidneys, bilateral tumors, or impaired renal function). Our group has demonstrated URS using the photodynamic diagnosis-guided dual laser ablation (PDD-DLA) technique (Yoshida T et al. Eur Urol Open Sci. 2021). In this analysis, we evaluated its long-term efficacy in patients with UTUC undergoing PDD-DLA. This study aimed to compare the efficacy of PDD-DLA versus the conventional holmium laser ablation (HLA) to evaluate oncological outcomes. METHODS: The study included ten consecutive patients with UTUC who underwent PDD-DLA between 2017 and 2019, and 16 consecutive patients who underwent HLA between 2006 and 2016 as a historical control group. The primary endpoint for the study was disease progression (defined as a relapsing tumor that could not be continued with a conservative approach and/or distant metastases). Secondary endpoints were to evaluate UTUC recurrence-free survival (RFS) and intravesical recurrence-free survival (IVRFS). The Kaplan-Meier method with log-rank test was used for survival analysis. RESULTS: The baseline characteristics were well balanced between the PDD-DLA and HLA groups in terms of tumor size, tumor grade, and multifocality. The disease progression-free rate was significantly higher among patients treated with PDD-DLA than in the HLA group (median survival: not reached vs. 33.9 months; p=0.025). The UTUC-RFS rate was not significantly different between the two groups (median survival: 21.0 vs. 8.8 months; p=0.139), The IVRFS rate was better in the PDD-DLA group when compared with those treated with HLA (median survival: not reached vs. 22.9 months; p=0.029). CONCLUSIONS: PDD-DLA was beneficial as a kidney-sparing surgery for UTUC with a 3-year follow-up. Furthermore, PDD-DLA prevented IVR when compared with the conventional method. Source of Funding: None © 2022 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 207Issue Supplement 5May 2022Page: e676 Advertisement Copyright & Permissions© 2022 by American Urological Association Education and Research, Inc.MetricsAuthor Information Takashi Yoshida More articles by this author Tadashi Matsuda More articles by this author Chisato Ohe More articles by this author Hidefumi Kinoshita More articles by this author Expand All Advertisement PDF DownloadLoading ...

PO-634-04 FLUOROLESS CRYOBALLOON ABLATION FOR PULMONARY VEIN AND LEFT ATRIAL POSTERIOR WALL ISOLATION IN PATIENTS WITH PERSISTENT ATRIAL FIBRILLATION: A SINGLE CENTER EXPERIENCE

Fluoroless electrophysiology procedure techniques have gained popularity for safely minimizing radiation exposure to patients and operators. While cryoablation for concomitant pulmonary vein isolation (PVI) and left atrial posterior wall isolation (PWI) have shown long-term efficacy in patients with persistent atrial fibrillation (AF), no studies have assessed the efficacy of the cryoablation utilizing a fluoroless technique.

A national service for delivering CD19 CAR-Tin large B-cell lymphoma - The UK real-world experience.

CD19 CAR-T have emerged as a new standard treatment for relapsed/refractory (r/r) large B-cell lymphoma (LBCL). CAR-T real-world (RW) outcomes published to date suggest significant variability across countries. We provide results of a large national cohort of patients intended to be treated with CAR-T in the UK. Consecutive patients with r/r LBCL approved for CAR-T by the National CAR-T Clinical Panel between December 2018 and November 2020 across all UK CAR-T centres were included. 404/432 patients were approved [292 axicabtagene ciloleucel (axi-cel), 112 tisagenlecleucel (tisa-cel)], 300 (74%) received the cells. 110/300 (38.3%) patients achieved complete remission (CR) at 6months (m). The overall response rate was 77% (52% CR) for axi-cel, 57% (44% CR) for tisa-cel. The 12-month progression-free survival was 41.8% (axi-cel) and 27.4% (tisa-cel). Median overall survival for the intention-to-treat population was 10.5m, 16.2m for infused patients. The incidence of grade ≥3 cytokine release syndrome and neurotoxicity were 7.6%/19.6% for axi-cel and 7.9%/3.9% for tisa-cel. This prospective RW population of CAR-T eligible patients offers important insights into the clinical benefit of CD19 CAR-T in LBCL in daily practice. Our results confirm long-term efficacy in patients receiving treatment similar to the pivotal trials, but highlight the significance of early CAR-T failure.

Dropouts From Sublingual Immunotherapy and the Transition to Subcutaneous Immunotherapy in House Dust Mite-Sensitized Allergic Rhinitis Patients.

Purpose: Both subcutaneous immunotherapy (SCIT) and sublingual immunotherapy (SLIT) are effective in reducing symptoms and medication scores and inducing long-term efficacy in patients with allergic rhinitis (AR). However, SLIT has been associated with poor patient adherence. This study investigates the factors impacting dropout rates from SLIT in house dust mite (HDM)-sensitized AR patients.Methods: A retrospective study was performed to analyze dropout rates and reasons in AR patients receiving Dermatophagoides farinae (Der f) SLIT with a follow-up period of 2 years.Results: A total of 719 HDM-sensitized AR patients received Der f-SLIT. Dropout rates increased with time and most occurred after 1 year of SLIT. By month 24, 654 (91%) patients had discontinued SLIT. The dropout rates by month 24 were 100, 90.1, and 91.1% in children <5 years old, children aged 5–18 years old, and adults ≥ 18 years old, respectively. Combination with allergic asthma and mono- or multi-sensitization to other aeroallergens did not affect the dropout rates. The most common self-reported reasons for dropouts were refusal of continuation, dissatisfaction with the efficacy, transition to SCIT, and adverse effects. Refusal of continuation increased with age, whereas transition to SCIT decreased with age. Ninety-seven cases transitioned from SLIT to SCIT, and the transition rates increased with time. Comorbid allergic asthma did not affect the transition rates. However, multi-sensitization was associated with a slightly higher rate of transition to SCIT. The most common reason for the transition was dissatisfaction with the efficacy (54.6%), which was only reported by patients older than 5 years. For children who began SLIT at younger than 5 years old, the most common reason (81.2%) for transition was age reaching 5 years.Conclusions: HDM-SLIT has a very high dropout rate, which is mainly due to refusal of continuation and dissatisfaction with the efficacy. Transitioning from SLIT to SCIT may help keep these patients on AIT and thus increase adherence and long-term efficacy.