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Key Points Primary hyperoxaluria type 1 is a genetic disorder associated with hepatic oxalate overproduction, kidney failure, and systemic oxalosis. Lumasiran treatment for up to 60 months was associated with sustained reductions in urinary and plasma oxalate and encouraging clinical outcomes. Lumasiran's safety profile was acceptable with mild injection site reactions being the most common adverse events. Background Primary hyperoxaluria type 1 (PH1) is characterized by hepatic oxalate overproduction, kidney stones, and progressive kidney disease. Lumasiran is the first approved treatment for PH1. Methods ILLUMINATE-A (NCT03681184) was a 60-month pivotal, phase 3, multinational clinical trial of lumasiran which consisted of a 6-month double-blind, placebo-controlled period (6M DB), followed by a treatment extension period of up to 54 months in which all patients received lumasiran. Eligible patients were aged ≥6 years with genetically confirmed PH1, eGFR ≥30 ml/min per 1.73 m 2 , and mean 24-hour urinary oxalate (UOx) excretion ≥0.70 mmol/24 h per 1.73 m 2 . Results Of 39 patients enrolled, 24 of 26 randomized to lumasiran in the 6M DB (lumasiran/lumasiran group) and 13 of 13 randomized to placebo in the 6M DB (placebo/lumasiran group) completed the study. Sustained reductions in 24-hour UOx were observed in both treatment groups. At month 60 relative to study baseline, the mean (SEM) 24-hour UOx percentage reductions were 54 (6) and 54% (8%) in the lumasiran/lumasiran and placebo/lumasiran groups, respectively, and the mean (SEM) plasma oxalate concentrations had decreased by 35 (5) and 38% (7%). eGFR remained stable through the end of the study in both treatment groups. Kidney stone event rates during the study were 0.47 (95% confidence interval, 0.36 to 0.62) and 0.54 (0.37 to 0.78) per patient-year in the lumasiran/lumasiran group and placebo/lumasiran group, respectively. Medullary nephrocalcinosis grade improved at the end of the study in 21 of 28 (75%) patients with nephrocalcinosis at baseline and an end of study assessment. The safety profile of lumasiran was acceptable. Injection site reactions were the most common adverse events during lumasiran treatment. Most adverse events were mild or moderate in severity. Conclusions Lumasiran treatment for up to 60 months in ILLUMINATE-A was associated with sustained reductions in UOx excretion and plasma oxalate concentration, encouraging clinical outcomes including stable eGFR in a population that would be expected to show eGFR decline, reduced kidney stone event rates, improved medullary nephrocalcinosis, and indications of improved health-related quality of life. Clinical Trial registry name and registration number: ClinicalTrials.gov NCT03681184. Podcast This article contains a podcast at https://dts.podtrac.com/redirect.mp3/www.asn-online.org/media/podcast/CJASN/2026_03_18_CJASNMar.21.3.31820.mp3

Abstract Follicular lymphoma (FL) is the most common indolent non-Hodgkin lymphoma. Although patients with FL have high response rates to therapy, most develop increasingly resistant disease. In addition, transformation into an aggressive lymphoma is associated with unfavorable outcomes. Many novel agents are under investigation, and early clinical data are encouraging. Aligning treatment with the underlying tumor biology and sequencing of therapies remain key clinical challenges. At the Lymphoma Research Foundation’s biannual 2024 Follicular Lymphoma Scientific Workshop, experts convened to discuss the role of chemotherapy in the context of new therapies, the impact of early progression on treatment sequencing, novel end points in clinical trials, disease biology and the tumor microenvironment, and new treatments on the horizon. This report focuses on updates in FL biology, first-line treatment, the role of progression of disease in 24 months, clinical trial design, and redefining cure in FL.

Abstract While the clinical focus on the sentinel lymph node biopsy (SLNB) is the presence of intra- or extra-nodal metastases, preclinical studies suggest that tumor-draining SLNB-associated vascular architecture and adhesion properties are altered regardless of SLNB positivity. Human intravital microscopy (HIVM) has defined blood vessel abnormalities that may impact lymphocyte adhesion and systemic drug delivery at primary melanoma sites. In this pilot study of HIVM during melanoma SLNB, we sought to determine the feasibility of obtaining HIVM observations of SLNB-associated vessels. We successfully performed HIVM in all 20 SLNB patients, and 7 were found to have nodal micrometastases by standard pathology. HIVM was capable of identifying both functional and non-functional SLNB-associated vessels based on the presence or absence of fluorescent dye uptake, respectively. Comparing vessel characteristics as a secondary objective, no statistically significant differences were noted in the diameter, flow rate, functionality, or shear stress of SLNB-associated blood vessels between positive and negative SLNBs, which may likely have been a reflection of the minimal disease burden. Nonetheless, these initial observations provide the framework to optimize future trials of HIVM in cancer patients.

ABSTRACT Background Ventricular tachycardia (VT) is a life‐threatening arrhythmia frequently observed in structural heart diseases, including LMNA‐related cardiomyopathy, a genetic disorder associated with high risk of sudden cardiac death and progressive systolic dysfunction. While catheter ablation is an established therapeutic option for VT, its efficacy in cardiac laminopathy remains poorly defined. Objectives To synthesize available evidence on the role and outcomes of VT ablation in patients with cardiac laminopathy. Methods A systematic review and single‐arm meta‐analysis was performed in accordance with PRISMA guidelines. PubMed, Embase, and Cochrane databases were searched for studies reporting VT ablation outcomes in LMNA‐related cardiomyopathy. An inverse variance random‐effects model was applied for meta‐analysis of proportions. Results Seven studies (six cohorts, one abstract) comprising 62 patients (mean age 53.2 ± 9.7 years; 85% male; 88% with implantable cardioverter‐defibrillator) were included. An endocardial/endo‐epicardial approach was used in 93% of cases. Acute procedural success was achieved in 37% (95% CI: 14%–63%; I² = 27.4%), and 28% required multiple procedures. Over a median follow‐up of 26 (9–35) months, VT recurrence occurred in 91% (95% CI: 76%–100%; I² = 37.2%). All‐cause mortality was 54% (95% CI: 39%–70%; I² = 28%), predominantly from cardiac causes (51%, 95% CI: 25%–76%; I² = 53%), and 14% (95% CI: 1%–34%; I² = 42%) underwent heart transplantation. Conclusions In LMNA‐related cardiomyopathy, catheter ablation is associated with high VT recurrence, limited long‐term success, and substantial cardiovascular mortality and transplantation rates, underscoring the importance of ICD implantation and the need for alternative strategies, including variant‐specific and molecularly targeted therapies.

PURPOSE Although most patients with follicular lymphoma (FL) can expect an indolent course, progressive lymphoma remains the primary cause of death during the first decade after diagnosis. Progression of disease within 24 months (POD24) of starting first-line (1L) immunochemotherapy defines a high-risk population with poor survival, but better risk stratification at diagnosis is needed. METHODS The FLIPI24 model was developed and internally validated to predict 24-month event rates using individual data from 4,485 patients treated with 1L immunochemotherapy from 10 observational cohorts of FL. Overall and cause-specific survival was further evaluated in FLIPI24 risk groups. External validation in the 1L immunochemotherapy setting was performed using the prospective observational Lymphoma Epidemiology of Outcomes (LEO) cohort (N = 565) and three randomized phase III trials (N = 3,192); extension to all patients with FL (any 1L therapy) was performed in the LEO cohort (N = 1,445) and its Molecular Epidemiology Resource subcohort (N = 1,074). RESULTS The FLIPI24 model uses age and four blood-based variables (hemoglobin, lactate dehydrogenase, beta-2 microglobulin, and WBC count). FLIPI24 showed consistent performance across validation and extension data sets, which was superior to existing prognostic tools. Across the four external immunochemotherapy validation data sets, patients with high-risk FLIPI24 (23%-32% of patients) had significantly higher 24-month event rates (22%-35%) and inferior 5-year overall survival (77%-83%) compared with patients with low-risk FLIPI24 (29%-31% of patients, 24-month event rates: 10%-12%; 5-year OS: 96%-97%). Results were consistent when evaluating lymphoma-related death and when extended to all patients with FL. CONCLUSION The FLIPI24 model robustly stratifies, at diagnosis, patients with FL at increased risk of lymphoma-related death versus patients with very low lymphoma-related mortality during the first decade after diagnosis. FLIPI24 can be used to enrich future clinical trial designs in newly diagnosed FL.