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Measurable residual disease (MRD) monitoring has become a critical component in the management of acute myeloid leukemia (AML), to inform prognosis, guide therapy, and serve as a key endpoint in clinical trials. The 2025 update of the MRD guideline provides a comprehensive and refined framework for MRD assessment, aligned with the ELN 2022 genetic risk classification. Developed by members of the ELN-DAVID consortium, the guidelines incorporate expert consensus determined through a two-stage Delphi round. They address the clinical implementation of MRD methodologies, technical considerations, integration into clinical trials, and future directions. Importantly, MRD recommendations are tailored to individual prognostic and genetic subgroups. A new qualitative MRD response category, designated as optimal, warning, or high risk of treatment failure, has been introduced to facilitate contextual interpretation of the MRD burden and its clinical relevance. Notably, ultrahigh-sensitivity (UHS) NGS-based MRD assessment is now recommended for FLT3-ITD-mutated AML following intensive chemotherapy and prior to allogeneic hematopoietic cell transplantation. A total of 56 recommendations were formulated, with 53 achieving a high level of consensus (≥90%). These updated guidelines represent a major step forward toward harmonizing MRD assessments in AML and enhancing its clinical utility across diverse treatment settings.
OBJECTIVES:To develop AutoReporter, a large language model (LLM) system that automates evaluation of adherence to research reporting guidelines. MATERIALS AND METHODS:Eight prompt-engineering and retrieval strategies coupled with reasoning and general-purpose LLMs were benchmarked on the SPIRIT-CONSORT-TM corpus. The top-performing approach, AutoReporter, was validated on BenchReport, a novel benchmark dataset of expert-rated reporting guideline assessments from 10 systematic reviews. RESULTS:AutoReporter, a zero-shot, no-retrieval prompt coupled with the o3-mini reasoning LLM, demonstrated strong accuracy (CONSORT 90.09%; SPIRIT: 92.07%), substantial agreement with humans (CONSORT Cohen's κ = 0.70, SPIRIT Cohen's κ = 0.77), runtime (CONSORT: 617.26 s; SPIRIT: 544.51 s), and cost (CONSORT: 0.68 USD; SPIRIT: 0.65 USD). AutoReporter achieved a mean accuracy of 91.8% and substantial agreement (Cohen's κ > 0.6) with expert ratings from the BenchReport benchmark. DISCUSSION:Structured prompting alone can match or exceed fine-tuned domain models while forgoing manually annotated corpora and computationally intensive training. CONCLUSION:Large language models can feasibly automate reporting guideline adherence assessments for scalable quality control in scientific research reporting. AutoReporter is publicly accessible at https://autoreporter.streamlit.app.
Many patients receiving frontline tyrosine kinase inhibitors (TKIs) for chronic phase chronic myeloid leukemia (CML-CP) experience inadequate disease control and/or adverse events (AEs) that impair quality of life. Treatments offering optimal efficacy, safety, and tolerability will support long-term therapy. In the primary analysis from ASC4FIRST, a phase 3 randomized trial comparing asciminib with investigator-selected TKIs (IS-TKIs) in newly diagnosed CML-CP, asciminib demonstrated superior efficacy vs all IS-TKIs and vs imatinib in the imatinib stratum, meeting both primary objectives. In the secondary analysis (2.2 years median follow-up), major molecular response (MMR) rate at week 96 was 74.1% with asciminib vs 52.0% with IS-TKIs (treatment difference, 22.4%; 95% CI, 13.6%-31.3%; 1-sided P<.001), and 76.2% with asciminib vs 47.1% with imatinib in the imatinib stratum (treatment difference, 29.7%; 95% CI, 17.6%-41.8%; 1-sided P<.001), meeting both key secondary objectives. MMR rate was 72.0% with asciminib vs 56.9% with second-generation (2G) TKIs (treatment difference, 15.1%; 95% CI, 2.3%-28.0%; 1-sided P<.05), suggesting possible clinical benefit although the study was not designed to formally confirm statistical significance for this secondary endpoint. Safety/tolerability remained favorable with asciminib vs IS-TKIs. Dose reductions and interruptions, respectively, occurred with asciminib (18.5% and 46.5%), imatinib (23.2% and 47.5%), and 2G TKIs (54.9% and 63.7%). The hazard ratio for time to discontinuation of treatment due to AEs for asciminib vs 2G TKIs was 0.46 (95% CI, 0.215%-0.997%). With longer follow-up, asciminib continued to demonstrate a favorable benefit-risk profile over IS-TKIs and imatinib, supporting its potential as a treatment option for newly diagnosed CML-CP.
Anti-CD19 Chimeric Antigen Receptor T-cell (CAR-T) immunotherapies have been funded in Canada for relapsed-refractory large B-cell lymphoma (RR-LBCL) after two lines of systemic therapy since late 2019. Real-world outcome data have been limited by lack of comparison to historical care. Using propensity-weighted analysis, we compared 3-year survival, healthcare resource utilization (HRU), and hospitalization events for patients with RR-LBCL treated with CAR-T (n=85) versus historical controls (HC) treated before CAR-T approval who would have been eligible based on present criteria (n=150). CAR-T 3-year overall survival (OS) was 59% ([95% CI, 42-72]; median not-reached) vs 10% ([95% CI, 5-16%]; median 4.4 months) in HC. 3-year CAR-T progression-free survival (PFS) was 48% ([95% CI, 32-63]; median 14.4 months) vs 6% ([95% CI, 3-11]; median 3.6 months) in HC. Hazard ratio (HR) for OS was 0.21 (95% CI, 0.14-0.31), and for PFS was 0.28 (95% CI, 0.2-0.39), comparing CAR-T vs HC. Per 1000 person-days at risk, CAR-T patients had fewer hospital admissions than HC (5.32 vs 9.1), emergency visits (2.33 vs 4.81), and intensive care admissions (0.53 vs 1.25), plus lower hospitalization rates for fever (0.93 vs 1.63), infection (1.48 vs 3.08), and neutropenia (0.66 vs 1.97; all p<0.001). CAR-T produced a sustained survival benefit and, despite well-described CAR-T toxicities, HC experienced more hospitalization events, underscoring the lack of effective salvage treatments. As one of the largest real-world comparisons of RR-LBCL patients receiving CAR-T vs previous standard-of-care, this study demonstrated its improved effectiveness and reduced HRU.
INTRODUCTION:While randomized clinical trials (RCT) confirmed superiority of Mepitel Film (MF) in reducing acute radiation dermatitis (ARD) compared to standard-of-care (SoC), the incremental cost difference has limited its use. A cost-effectiveness analysis (CEA) was conducted from a Canadian healthcare payer's perspective to guide policy decisions. METHODS:A decision model was constructed to perform a CEA for MF compared to SoC (moisturizers) for prevention of grade 2 or higher ARD following adjuvant hypo-fractionated whole-breast radiotherapy (RT) based on a Canadian multicentre RCT. Direct and indirect cost data were collected from two oncology centers in Canada. Quality-of-life (QoL) utility values were derived from mapping Dermatology Life Quality Index (DLQI) scores for patients with grade 2 or higher ARD at week 6 of RT to EQ-5D. A willingness-to-pay (WTF) threshold of CAD 50,000 per quality-adjusted life years (QALY) gained was used. Deterministic and probabilistic sensitivity analyses were performed to address uncertainty in decision model assumptions. RESULTS:Base case analysis demonstrated that MF is cost-effective in preventing grade 2 or higher ARD as compared with SoC with an incremental cost-effectiveness ratio (ICER) of CAD 3366 per QALY gained. When indirect costs were included, MF resulted in an ICER of CAD 2823 per QALY gained. One-way sensitivity analysis showed that the results were most sensitive to the QoL utility value for ARD. Probabilistic sensitivity analysis confirmed that MF demonstrates 100% probability of cost-effectiveness at a $50,000 per QALY threshold. CONCLUSIONS:MF is a cost-effective intervention for preventing high-grade ARD and should be recommended for patients with breast cancer undergoing adjuvant RT.
