Background Expanded molecular diagnostics and introduction of azacitidine plus venetoclax have reshaped acute myeloid leukemia (AML) management. However, real-world data on these impacts in Southeast Asia remain limited. Objectives To evaluate clinical outcomes across two implementation eras defined by expanded molecular testing and adopting of azacitidine plus venetoclax. Design Retrospective single-center cohort study. Methods We included adults with newly diagnosed AML, comparing early (2016-2020) and later (2021-2025) eras. The primary endpoint was the adjusted between-era difference in 24-month restricted mean survival time (RMST) for overall survival (OS). Secondary approaches included propensity score matching (PSM) to adjust for baseline imbalances and a 6-month landmark analysis to evaluate allogeneic stem cell transplantation (alloSCT) outcomes without immortal time bias. Results Among 285 patients, 228 received AML-directed therapy (early n=107; later n=121). Later-era patients were significantly older and more frequently classified as ELN adverse risk, coinciding next-generation sequencing implementation (22.3%). Adjusted 24-month RMST for OS did not differ between eras (difference -0.06 months; 95% CI -2.41 to 2.27; p = 0.956). To control for referral bias, a 1:1 PSM yielded 84 well-balanced pairs (n=168). Within this matched cohort, median OS (15.4 vs. 14.7 months; HR 1.02; p = 0.908) and relapse-free survival remained comparable between eras. In the 6-month landmark analysis of the PSM subset, alloSCT demonstrated a clinical trend toward reduced mortality (adjusted HR 0.69, 95% CI 0.34 to 1.38). Conclusion Despite major shifts in treatment patterns, no improvement in adjusted short-term survival was observed at the population level. Notably, the higher proportion of adverse risk patients in the later era likely reflects both enhanced molecular ascertainment and changes in referral patterns, rather than a pure biological shift alone. Expanding transplant access and comprehensive molecularly guided therapy remain key priorities.
Background Janus kinase (JAK) inhibitors are used as first-line treatment for myelofibrosis (MF) and are associated with improvements in splenomegaly and disease-related symptoms. However, a substantial proportion of patients experience treatment failure or intolerance, and outcomes after discontinuation remain poor. Although international groups have proposed criteria for JAK inhibitor failure, standardized and operational definitions applicable to real-world practice, particularly in South Korea, are lacking. Objectives This study aimed to establish expert consensus on defining first-line ruxolitinib failure and to develop practical transition strategies tailored to the Korean clinical context. Design This was a non-interventional qualitative study using a modified Delphi methodology. Methods Fourteen hematologists specializing in MF in South Korea participated in a two-round web-based Delphi survey followed by a final consensus meeting. Consensus-driving questions covered five domains: ruxolitinib failure, loss of therapeutic response, disease progression, intolerance, and transition strategies. Consensus was defined as ≥80% agreement using predefined criteria. Results Consensus was achieved on key operational definitions across the major domains, although several intolerance-related items remained unresolved. Refractory MF was defined as inadequate spleen response (<10% reduction after ≥6 months of therapy) or inadequate symptom response (<30% reduction in MPN-SAF score after ≥3 months of therapy). Clear criteria for response loss, progressive splenomegaly, hematologic progression, and intolerance were established. Structured tapering of ruxolitinib (≥4 weeks), management of ruxolitinib discontinuation syndrome, and transition strategies including use of second-line JAK inhibitors and prioritization of allogeneic hematopoietic stem cell transplantation were agreed upon. Conclusion This modified Delphi study successfully established consensus-based recommendations for ruxolitinib failure and treatment transition in MF management in Korea. The findings provide practical criteria for identifying treatment failure and guiding transition strategies, ensuring alignment with global best practices while addressing local healthcare considerations.
Hematological malignancies represent a significant challenge in both diagnosis and treatment, constituting a substantial portion of global cancer cases. The integration of biomarkers into the diagnostic and therapeutic processes is essential but remains underexplored in the context of precision medicine. This review synthesizes the current literature on established and emerging biomarkers, including monoclonal immunoglobulins, beta-2 microglobulin, cytogenetic and molecular markers, and liquid-biopsy-based markers, and their diagnostic, prognostic, and predictive applications across leukemia, lymphoma, and multiple myeloma. We describe how these biomarkers are used in current clinical practice to support diagnosis, risk stratification, and treatment selection, based on the published evidence base for each marker. Overall, validated biomarkers have improved diagnostic accuracy, risk stratification, and therapeutic decision-making, while emerging biomarkers require further clinical validation. Although several biomarkers are now incorporated into routine clinical care, ongoing validation of emerging biomarkers will be critical for expanding precision oncology approaches in hematologic malignancies.
Background Emicizumab, a bispecific monoclonal antibody, substitutes for activated factor (F)VIII, facilitating hemostasis in people with hemophilia A (HA). HAVEN 6 is a multicenter, open-label, single-arm phase 3 study of emicizumab in people with mild or moderate HA. At primary data cut-off, emicizumab demonstrated clinically meaningful bleed control and a favorable safety profile. Objectives To evaluate the long-term efficacy and safety of emicizumab in HAVEN 6. Methods Participants had mild (FVIII >5–<40 IU/dL) or moderate (FVIII ≥1–≤5 IU/dL) HA without FVIII inhibitors, warranting prophylaxis as assessed by the treating physician. Safety endpoints included adverse events (AEs) and AEs of special interest (e.g. thromboembolic events [TEs] and thrombotic microangiopathies). Efficacy endpoints included annualized bleed rates (ABR) for treated bleeds. Pharmacokinetics (PK), pharmacodynamics (PD), safety biomarkers of coagulation, and F8 genotypes were assessed. Further study details are published in the primary analysis (Négrier et al. Lancet Haematol 2023). Results At cut-off (December 11, 2023), median (interquartile range) follow-up was 155.9 (24.1–192.6) weeks (N = 72). In total, 481 AEs were reported; 93.1% of participants experienced ≥1 AE. Two TEs occurred, one since the primary analysis. Both participants continued emicizumab. Model-based ABR for treated bleeds was 1.0 (95% confidence interval: 0.71–1.35). Therapeutic emicizumab exposure levels were maintained throughout the study. FXIa-triggered thrombin generation peak height was higher compared with levels previously observed in people with severe HA. Safety biomarkers of coagulation were unaffected by emicizumab. F8 genotyping of participants found variants consistent with mild or moderate HA. Conclusions These long-term efficacy and safety data confirm emicizumab as a valuable treatment option for people with non-severe HA.
Background Chronic lymphocytic leukemia (CLL)/small lymphocytic lymphoma (SLL) is a clonal mature B-cell neoplasm with rare extranodal organ renal involvement. Objectives To summarize the clinical and pathological characteristics of biopsy-confirmed CLL/SLL-associated renal lesions and evaluate the efficacy of targeted combination therapy. Design Retrospective multicenter observational study. Methods Eleven patients with CLL/SLL-associated nephropathy were enrolled from January 2017 to October 2024 across three Chinese centers. As of December 31, 2025, data were collected through electronic medical records and telephone follow-up. Results The median age was 58 (range 40–72) years. Among tested patients, 88.9% (8/9) exhibited IGHV mutation and 62.5% (5/8) were CLL-IPI low-risk, and no TP53 mutations were detected. The median time from CLL diagnosis to renal biopsy was 40.7 months (range: 0.2–58 months). Biopsy indictions included proteinuria (90.9%, 10/11), hematuria (54.5%, 6/11), renal dysfunction (54.5%, 6/11), and nephrotic syndrome (9.1%, 1/11). Main pathologies were tumor cell interstitial infiltration (45.5%, 5/11), membranoproliferative glomerulonephritis (27.3%, 3/11), membranous nephropathy (18.2%, 2/11), and C3 glomerulonephritis (9.1%, 1/11). Concomitant monoclonal gammopathy and cryoglobulinemia were observed in 27.3% and 18.2%, respectively. Nine patients received BTKi -based therapy. The best overall response rate (ORR) for CLL/SLL was 100%, with a CR rate of 72.7%. According to KDIGO 2021 guidelines, the renal best ORR was 100%, with a CR rate of 36.4%. Four patients achieved CR in both CLL and renal assessments. As of December 31, 2025, the median follow-up was 70.1 months and median PFS was not reached. Grade ≥3 hematologic toxicities included neutropenia (27.3%) and thrombocytopenia (18.2%). Common non-hematologic adverse events were COVID-19 (27.3%), bleeding (18.2%), and gastrointestinal symptoms (18.2%), all of grade 1-2. Conclusions CLL/SLL with renal involvement is associated with a favorable IGHV-mutated profile. Interstitial infiltration and membranoproliferative glomerulonephritis are the predominant renal pathologies. BTKi-based regimens were associated with favorable hematologic and renal outcomes in this small cohort.
