Citations

Abstract Little is known about risk factors for central nervous system (CNS) relapse in mature T-cell and natural killer cell neoplasms (MTNKNs). We aimed to describe the clinical epidemiology of CNS relapse in patients with MTNKN and developed the CNS relapse In T-cell lymphoma Index (CITI) to predict patients at the highest risk of CNS relapse. We reviewed data from 135 patients with MTNKN and CNS relapse from 19 North American institutions. After exclusion of leukemic and most cutaneous forms of MTNKNs, patients were pooled with non-CNS relapse control patients from a single institution to create a CNS relapse–enriched training set. Using a complete case analysis (n = 182), including 91 with CNS relapse, we applied a least absolute shrinkage and selection operator Cox regression model to select weighted clinicopathologic variables for the CITI score, which we validated in an external cohort from the Swedish Lymphoma Registry (n = 566). CNS relapse was most frequently observed in patients with peripheral T-cell lymphoma, not otherwise specified (25%). Median time to CNS relapse and median overall survival after CNS relapse were 8.0 and 4.7 months, respectively. We calculated unique CITI risk scores for individual training set patients and stratified them into risk terciles. Validation set patients with low-risk (n = 158) and high-risk (n = 188) CITI scores had a 10-year cumulative risk of CNS relapse of 2.2% and 13.4%, respectively (hazard ratio, 5.24; 95% confidence interval, 1.50-18.26; P = .018). We developed an open-access web-based CITI calculator (https://redcap.link/citicalc) to provide an easy tool for clinical practice. The CITI score is a validated model to predict patients with MTNKN at the highest risk of developing CNS relapse.

Background Comparative evaluations of preventive migraine treatments can help inform clinical decision making for managing migraine in clinical practice. Methods An anchored matching-adjusted indirect comparison analysis was conducted using pooled participant-level data from two phase 3 atogepant trials (ADVANCE and PROGRESS) and one phase 2/3 rimegepant trial (BHV3000-305) to evaluate the relative efficacy and safety/tolerability of atogepant and rimegepant as preventive migraine treatments. Participants receiving atogepant 60 mg once daily, rimegepant orally disintegrating tablet 75 mg once every other day, and placebo were included. Only participants meeting the BHV3000-305 inclusion/exclusion criteria were analyzed: ≥6 monthly migraine days and ≤18 monthly headache days at baseline. The primary efficacy assessment of interest was change in monthly migraine days across weeks 1–12. Results There were 252 participants in the atogepant group and 348 in the rimegepant group. Across weeks 1–12, atogepant 60 mg demonstrated a significantly greater reduction in mean monthly migraine days compared with rimegepant 75 mg (mean difference [95% CI]: −1.65 [−2.49, −0.81]; p < 0.001). Both atogepant and rimegepant demonstrated similar safety/tolerability profiles. Conclusion In this matching-adjusted indirect comparison analysis, oral atogepant 60 mg once daily demonstrated a significantly greater reduction in monthly migraine days compared with rimegepant 75 mg orally disintegrating tablet once every other day.

AbstractBackgroundThis study examined the trajectory of health‐related quality of life (HRQoL) for patients with clinical stage N0 HNSCC enrolled in ACRIN 6685 who underwent elective neck dissection(s).MethodsHRQoL of 230 patients in the ACRIN 6685 trial was measured prospectively up to 2 years following surgery using the University of Washington Quality of Life instrument.ResultsGeneral Health Within the Last 7 Days did not differ significantly from baseline at any follow‐up. General Health Relative to Before Cancer fell significantly by 5.8 points following surgery (p = 0.048), and then returned to 3.0 points above baseline at 1 year (p = 0.65). For Overall Quality of Life, HRQoL fell significantly by 4.3 points following surgery (p = 0.031) and then returned to levels not significantly different from baseline.ConclusionsPatients with stage N0 HNSCC experience significant declines in HRQoL immediately following surgery, including neck dissection, which recovers to near or better than baseline within 1–2 years.

Abstract Background Risankizumab (RZB), a monoclonal antibody targeting interleukin-23 p19, was evaluated for maintenance therapy in patients with moderately to severely active ulcerative colitis (UC) and clinical response to RZB intravenous (IV) induction treatment in a phase 3 double-blind, placebo (PBO)-controlled withdrawal (WD) maintenance study, COMMAND (NCT03398135). Methods Patients with moderately to severely active UC who achieved a clinical response per Adapted Mayo score after 12 or 24 weeks (wks) of RZB IV treatment in the phase 2b and phase 3 INSPIRE induction studies (NCT03398148)1 were randomized 1:1:1 in COMMAND to RZB 180 mg (RZB180), 360 mg (RZB360), or PBO (RZB withdrawal) subcutaneous (SC) treatment every 8 wks for 52 wks. The efficacy analysis included responders to 12 wk of RZB IV, while the safety analysis included responders to 12 or 24 wk of RZB IV. The primary endpoint was clinical remission per Adapted Mayo score at wk 52. Key secondary endpoints included endoscopic improvement, HEMI, endoscopic remission, steroid-free clinical remission, maintenance of clinical remission, no bowel urgency, and no abdominal pain at wk 52. Results At baseline of induction, demographics and disease characteristics were similar between treatment groups; 75% of 548 patients had history of inadequate response or intolerance to ≥ 1 advanced therapy (AT). Patients receiving RZB180 (40.2%) and RZB360 (37.6%) achieved significantly higher rates of clinical remission vs WD (25.1%) (adjusted treatment difference vs WD: 16.3% and 14.2%, respectively; P ≤ .01) (Fig. 1A). Greater proportions of patients achieved endoscopic improvement, HEMI, endoscopic remission, steroid-free clinical remission, maintenance of clinical remission, no bowel urgency, and no abdominal pain with RZB180 and RZB360 vs WD (Fig. 1B). The overall rates of adverse events (AEs), and serious infections were similar among treatment groups (Table 1). Serious (presented as events/100 patient-years [E/100 PY]) (RZB180: 5.9; RZB360: 6.3; WD: 11.4) and severe AEs (RZB180: 1.6; RZB360: 4.0; WD: 8.0) were lower in the RZB arms vs WD. No active tuberculosis, adjudicated anaphylaxis, serious hypersensitivity, or adjudicated major adverse cardiovascular events were reported in any treatment group. Conclusion In patients with moderately to severely active UC responding to 12-week RZB induction therapy, RZB maintenance dosing with 180 mg and 360 mg SC was superior to placebo in achieving clinical remission as well as other key clinical, endoscopic, and histological-endoscopic endpoints. RZB was well-tolerated, with no new safety concerns observed.

Background: We have previously demonstrated by performing a genome-wide association study that a genetic locus resulting in ↓CDCP1 expression was associated with myocardial recovery in patients with dilated cardiomyopathy (DCM). We have subsequently shown that ↓CDCP1 decreases human cardiac fibroblast proliferation in vitro , however, its potential role in modulating cardiac fibrosis and function in vivo is unknown. Methods: A Cdcp1 knock-out (KO) mouse was generated on FVB/NJ background. Angiotensin II/Phenylephrine (AngII/PE) or saline was infused by an osmotic pump into mice ( Cdcp1 KO n=20; wild type/wt n=18) for 4 weeks. Echocardiography was performed at 0 and 4 weeks. Picrosirius red (PSR) staining was performed on cross-sectional heart tissue to identify cardiac fibrosis, which was quantified, using ImageJ software, as a percentage of left ventricular (LV) area stained by PSR. Results: LV mass index (LVMI) significantly increased in AngII/PE wt mice as compared to saline wt (figure a. 3.65±0.15 mg/g vs 3.05±0.17mg/g, p=0.01), however, AngII/PE Cdcp1 KO mice had significantly decreased LVMI as compared to AngII/PE wt mice (figure a. 3.17±0.09 mg/g vs 3.65±0.15 mg/g, p=0.01). In addition, fractional shortening trended higher in AngII/PE Cdcp1 KO mice as compared to AngII/PE wt mice (figure b. 50.36±2.06% vs 45.48±1.43%, p=0.07). Extent of cardiac fibrosis was significantly higher in AngII/PE wt mice as compared to saline wt (figure c. 15.79±0.49% vs 7.93±0.39%, p<0.0001), however AngII/PE Cdcp1 KO mice had significantly reduced cardiac fibrosis as compared to AngII/PE wt mice (figure c. 9.41±0.43%, p<0.0001). Conclusions: CDCP1 KO significantly reduces pressure over-load induced LV hypertrophy and cardiac fibrosis. Its role as a novel therapeutic target in attenuating fibrosis and improving cardiac function in DCM needs to be further explored.

Introduction: Chronic lymphocytic leukaemia (CLL) is the most common leukaemia type. In 2020, there were an estimated 207,463 people living with CLL, with an annual incidence of approximately 4.9 per 100,000 in the United States (US). Zanubrutinib is a Bruton tyrosine kinase inhibitor that is FDA-approved and an NCCN preferred and recommended treatment of CLL. In the phase 3 ALPINE trial (NCT03734016), zanubrutinib elicited a significantly higher overall response rate and significantly longer progression-free survival (PFS) than ibrutinib. This study aimed to compare zanubrutinib versus ibrutinib in Relapsed/Refractory (R/R) CLL by calculating the number needed to treat (NNT) to avoid one progression or death and associated incremental costs. Methods:A health-economic model was developed to evaluate the number of R/R CLL patients needed to be treated to avoid a progression or death from the US payer perspective. Payer blend was assumed with 40% Commercial and 60% Medicare payer mix. Clinical efficacy data were extracted from the ALPINE trial. Final analysis result of 24-month PFS (79.5% for zanubrutinib and 67.3% for ibrutinib) was used for the base-case analysis in the model. Treatment, adverse event management, other medical resource use, and subsequent treatment costs were considered in the model. The NNT, incremental cost per treated patient, and incremental cost per additional patient with progression or death were captured. Deterministic sensitivity analyses were conducted to assess parameter uncertainties and explore key model drivers. Scenario analyses were conducted to test the impact of different PFS estimates. Results: The base-case results fromthe NNT model showed that for every 8 patients treated with zanubrutinib, 1 event of progression or death would be avoided compared to using ibrutinib. The total costs per patient treated with zanubrutinib and ibrutinib are $370,558 and $430,150, respectively, with a cost savings of $59,593 associated with using zanubrutinib (Table). Drug costs and PFS have the greatest impact on the incremental cost per patient. Varying the PFS scenarios, including adjustment with drug interruption, COVID death, or treatment discontinuation, change the NNT from 8 to 12, and are associated with cost savings of $58,179 to $67,153 per zanubrutinib-treated patient in a 24-month time frame. Applying the model result to a hypothetical scenario of a clinical practice of 100 patients treated with zanubrutinib versus ibrutinib suggest that approximately 13 patients will avoid disease progression events or death. Conclusions: The NNT model suggests thatusing zanubrutinib to treat R/R CLL patients, compared to ibrutinib, will result in more favorable clinical and economic outcomes in the US.