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This guideline has been updated. This ASCO Living Guideline is reviewed on an eight-week cycle. Please see the online dynamic version for the latest updates. ASCO Guidelines provide recommendations with comprehensive review and analyses of the relevant literature for each recommendation, following the guideline development process as outlined in the ASCO Guidelines Methodology Manual . ASCO Guidelines follow the ASCO Conflict of Interest Policy for Clinical Practice Guidelines . Clinical Practice Guidelines and other guidance (“Guidance”) provided by ASCO is not a comprehensive or definitive guide to treatment options. It is intended for voluntary use by clinicians and should be used in conjunction with independent professional judgment. Guidance may not be applicable to all patients, interventions, diseases or stages of diseases. Guidance is based on review and analysis of relevant literature, and is not intended as a statement of the standard of care. ASCO does not endorse third-party drugs, devices, services, or therapies and assumes no responsibility for any harm arising from or related to the use of this information. See complete disclaimer in Appendix 1 and Appendix 2 (online only) for more . PURPOSE To provide updated guidance regarding the therapy for multiple myeloma. METHODS ASCO and Ontario Health (Cancer Care Ontario) convened a joint Expert Panel and conducted an updated systematic review of the literature. RESULTS The updated review identified a total of 161 relevant randomized trials. UPDATED RECOMMENDATIONS Daratumumab therapy may be offered to patients with high-risk smoldering myeloma. Quadruplet therapy with daratumumab or isatuximab, combined with bortezomib, lenalidomide, and dexamethasone, should be offered as initial therapy for transplant eligible patients. They should also be offered at least lenalidomide maintenance, with or without daratumumab, carfilzomib, and/or dexamethasone. Quadruplet therapy with daratumumab or isatuximab, combined with bortezomib, lenalidomide, and dexamethasone, should be offered as therapy for suitable transplant-ineligible patients. Patients with relapsed or refractory multiple myeloma should be offered triplet therapy or T-cell redirecting therapies according to a set of recommended principles. Additional information is available at www.asco.org/hematologic-malignancies-guidelines .

Background: There is no consensus scoring system for staging and prognosis in hepatocellular carcinoma (HCC), which is the fourth leading cause of cancer-related mortality worldwide. Commonly used systems include the albumin–bilirubin (ALBI) score, the Barcelona staging classification (Barcelona Clinic Liver Cancer, BCLC), the Model for End-Stage Liver Disease (MELD), and the model to estimate survival in ambulatory HCC patients (MESIAH). Liver secretion of pseudocholinesterase (PCHE) has been linked to liver function but is poorly studied in the natural history of HCC. We evaluated whether serum PCHE level predicts HCC mortality and whether it enhances existing scoring systems. Methods: We conducted a retrospective cohort study of individuals diagnosed with HCC. We collected variables including PCHE level, clinical data used in scoring systems, and time to mortality or liver transplant. We then analyzed the association between these variables and survival using Kaplan–Meier curves, Cox proportional hazards regression models, receiver operating characteristic (ROC) curves, and area under the curve (AUC) calculations. Results: We identified 420 individuals with HCC who were tested for PCHE levels, with a follow-up time of more than 20 years. There was a strong inverse relationship between PCHE level and overall survival, with the lowest quartile having high mortality and poor outcomes. Low PCHE level was associated with hepatitis C virus (HCV) infection, vascular invasion, poor liver function, and a high likelihood of liver transplant. In contrast, the highest quartile was associated with metabolic dysfunction–associated steatotic liver disease (MASLD) as the underlying cause. Compared with validated scoring systems, ALBI, BCLC, MELD 3.0, and MESIAH, the PCHE level was an independent predictor of mortality. PCHE levels could predict 3-month survival as well as or better than the other scoring systems, with an AUC of 0.74. PCHE level could also predict mortality related to hepatectomy. The addition of PCHE level to MESIAH and ALBI scoring systems could further improve the ability to predict overall mortality in HCC. Conclusions: PCHE is a reliable stand-alone biomarker of HCC prognosis. It is an independent predictor of mortality and can improve the accuracy of existing scoring systems. Improved risk stratification could improve outcomes by informing treatment decisions regarding hepatectomy or other interventions.

Key Points This study reveals the temporal development and progression of senescence in an arteriovenous fistula of uremic mice. Senescent genes including p21 increased 7 days after arteriovenous fistula placement, and p16 and phosphorylated p53 cells accumulate between days 14 and 28. Transcriptomic analyses confirm established genes in arteriovenous fistula failure and suggest a collection of novel genes of interest. Background Hemodialysis therapy for ESKD requires suitable vascular access, most commonly the arteriovenous fistula (AVF). Forty percent of AVFs fail within 1 year, leading to morbidity and care costs. Failure mechanisms remain unclear, and current therapies are inadequate. Cellular senescence may be critical in AVF failure, and ESKD itself may accelerate senescence and subsequent vascular dysfunction. Senescence follows AVF placement in rodents with normal kidney function, but the temporal and spatial features in uremic conditions are unknown. This study aimed to characterize AVF changes in uremic mice over time and versus control vessels. Methods Six- to eight-week-old male C57BL6/J mice underwent five/six nephrectomy. Twenty-eight days later, an AVF was created by cuff anastomosis (right carotid artery to the right jugular vein). Transcriptomic analysis was performed 7 days post-AVF, and further samples were collected at 14 and 28 days post-AVF creation for histologic assessment. Results AVF outflow vein morphometry showed reduced neointimal cell density. Whole transcriptomic analysis of outflow versus control veins at 7 days post-AVF placement revealed 1187 upregulated and 3256 downregulated genes. Differentially expressed genes were significantly enriched in two established senescence-related gene sets, SenMayo (a curated panel of approximately 125 genes validated across species to capture senescence and associated proteins) and SenSig (a broader panel assessed to represent fibrotic and stress-induced cell response). Histologically, senescence markers p16, p21, and phospho53 increased between days 14 and 28. Genes common to our dataset, SenMayo, and SenSig were validated with quantitative reverse transcription PCR. Conclusions These data support established markers of AVF failure, such as matrix-metalloproteinases and monocyte chemokines, and identify potential novel modulators of AVF survival that may inform senolytic strategies to improve patency. In summary, this study reveals for the first time the chronologic progression of vascular senescence in the AVF of uremic mice.

Abstract Viral infections are estimated to contribute to 12% to 20% of all cancers worldwide, with virus-driven malignancies disproportionately affecting low- and middle-income countries, whereas metabolic and nonviral factors predominate in high-income regions. Key oncogenic viruses that cause solid tumors include high-risk human papillomaviruses, Epstein–Barr virus, hepatitis B virus, hepatitis C virus, Kaposi sarcoma–associated herpesvirus, and Merkel cell polyomavirus. Immune checkpoint inhibitors (ICI) have revolutionized cancer therapy by boosting immune responses against tumors. Although viral infection–associated tumors often exhibit “hot” immune profiles, clinical outcomes with ICIs remain inconsistent. Some studies report improved survival in virus-associated cancers, whereas others indicate no clear benefit, which might reflect high variability in tumor microenvironments and immune responses. In this review, we aim to explore the direct and indirect contribution of different viruses to carcinogenesis in solid tumors, with a particular focus on immunotherapy effectiveness based on infection status.

Lay Summary This multicenter study evaluated clinical outcomes in pregnancy for women with ulcerative colitis and an ileal pouch-anal anastomosis. Close monitoring is needed with a multidisciplinary team for management of inflammatory complications of the pouch such as pouchitis in pregnancy and postpartum.

Abstract Aims Heart failure (HF) with preserved (HFpEF) and mildly reduced (HFmrEF) ejection fraction are prevalent, yet frequently underdiagnosed syndromes associated with high morbidity and mortality, impaired quality of life, and escalating healthcare expenditures. Although guideline-directed medications like SGLT2 inhibitors have been shown to reduce the risk of hospitalization and cardiovascular death, their use remains limited and substantial residual risk persists. This trial aims to evaluate the safety and performance of a novel left-atrium-to-coronary-sinus shunt (Edwards APTURE transcatheter shunt system) in HFpEF and HFmrEF patients. Methods ALT-FLOW II is a prospective multi-centre, randomized, sham-controlled, double-blinded (patient and assessor) trial. Approximately 100 symptomatic HF patients aged ≥18 years with left ventricular ejection fraction >40% and exercise pulmonary capillary wedge pressure (PCWP) ≥25 mm Hg with a PCWP to right atrial pressure gradient ≥8 mm Hg will be randomized 1:1 to the APTURE shunt vs sham control. Key exclusion criteria include severe HF, significant valvular disease, and more than mild right ventricular dysfunction. The primary endpoints are the safety of the APTURE device at 30 days and change in workload-corrected PCWP normalized to bodyweight at 6 months. Secondary endpoints include changes in patient-reported outcomes, and hemodynamic and echocardiographic parameters through 5 years. The trial will also explore the impact of the device on short-term cardiac remodelling and intra-cardiac flow patterns using multi-modality imaging. Conclusions The ALT-FLOW II trial will evaluate the safety and performance of the APTURE system in symptomatic HFpEF and HFmrEF patients with elevated left atrial pressure.

Abstract Introduction Cardiovascular disease (CVD) is the leading cause of death among patients with kidney failure on dialysis. Social determinants of health may worsen this risk but are seldom incorporated into prognostic models. ICD-10 Z-codes provide standardized documentation of social determinants of health, yet their prognostic value in dialysis populations remains uncertain. This study examined whether Z-coded social determinants of health are associated with adverse cardiovascular outcomes and mortality among patients receiving dialysis for kidney failure. Methods A retrospective cohort study was conducted using the TriNetX Research Network (2010–2024), encompassing de-identified data from 103 institutions. Adults with kidney failure on chronic dialysis were stratified by the presence of ICD-10 Z-codes (Z55–Z65). Propensity score matching (1:1) balanced demographics, comorbidities, medications, and laboratory values. Primary outcomes were all-cause mortality and hospitalization; secondary outcomes included acute heart failure, myocardial infarction, stroke, cardiac arrest, bradyarrhythmias, and ventricular tachycardia. Results After matching, mean age was 62 years, and 42.4% were female in the Z-code cohort versus 41.2% in controls. Over one year, mortality occurred in 12.5% versus 10.9% (hazard ratio [HR], 1.22; 95% confidence interval [CI], 1.15–1.29) and all-cause hospitalizations in 57.3% versus 53.1% (HR, 1.22; 95% CI, 1.19–1.26). Cardiovascular complications were consistently higher in Z-coded patients, including heart failure (24.3% vs 20.5%; HR, 1.29), myocardial infarction (8.0% vs 7.1%; HR, 1.19), stroke (6.6% vs 6.2%; HR, 1.13), cardiac arrest (3.8% vs 3.1%; HR, 1.29), and bradyarrhythmias (6.9% vs 5.5%; HR, 1.33). Discussion Among patients with kidney failure, documented Z-coded social risk factors were associated with greater mortality and cardiovascular morbidity. Incorporating social determinants of health documentation into nephrology care may improve risk stratification and inform targeted interventions.