Tasigna (nilotinib) / Novartis, Inhibikase - LARVOL DELTA

Imatinib in chronic myeloid leukemia: A comparative assessment of patients in pivotal clinical trials and real-world settings (ASH 2025) - " We included the imatinib arm of 5 pivotal CTs: the IRIS, which established the superiority of imatinib over interferon alfa plus cytarabine, and the DASISION, ENESTnd, BFORE, and ASC4FIRST trials, which supported the approvals of dasatinib, nilotinib, bosutinib, and asciminib, respectively. Patients in the RWD cohort exhibited higher clinical risk profiles, greater racial and ethnic diversity, and longer intervals between diagnosis and treatment initiation. These factors may contribute to the lower rates of achieving optimal treatment responses, including cytogenetic and molecular milestones. Despite these differences, long-term outcomes were comparable, aligning with current trends showing that survival in CML patients now approaches that of the general population."

Clinical • Real-world • Real-world evidence • Chronic Myeloid Leukemia • Hematological Malignancies • Leukemia • ABL1

Model-based evaluation of clinical outcomes for ponatinib versus 2G TKIs in third-line chronic myeloid leukemia (CML) (ASH 2025) - "Objectives: To estimate and compare ponatinib versus 2G TKIs (bosutinib, dasatinib, nilotinib) in adult patients with CP-CML who have received two prior TKIs, focusing on long-term clinical and economic outcomes: survival (life years), quality-adjusted survival (QALYs), and healthcare resource utilization (outpatient, inpatient and emergency department visits). This model-based analysis suggests that ponatinib offers substantial clinical benefits over 2G TKIs in the third-line treatment of CP-CML, particularly for patients with the T315I mutation. These findings support the clinical value of ponatinib as a preferred treatment option in this setting, with the potential to improve survival outcomes and reduce burden to the healthcare system."

Clinical • Clinical data • Chronic Myeloid Leukemia • Hematological Malignancies • Leukemia

Timing of tyrosine kinase inhibitor switching and long-term outcomes in chronic myeloid leukemia: A real-world comparative study (ASH 2025) - "This study evaluates the comparative safety and effectiveness of early switching (<3 months), late switching (≥6 months), and continued first-line TKI therapy across imatinib, dasatinib, and nilotinib. Switch timing in CML has substantial prognostic implications. Early TKI switching, especially within the first 3 months, is associated with higher mortality and complications. Late switching may be better tolerated, particularly with second-generation agents."

Clinical • Real-world • Real-world evidence • Chronic Myeloid Leukemia • Congestive Heart Failure • Diabetes • Heart Failure • Hematological Malignancies • Leukemia • Metabolic Disorders

Asciminib as initial therapy with addition of lower dose tyrosine kinase inhibitors (TKIs) for patients with chronic myeloid leukemia who do not achieve optimal response or a deep molecular remission (ASH 2025) - P2 | "Patients who did not achieve MR4.5 after 24 months on asciminib, experienced treatment failure at any time or had a warning response at 12 months were offered the addition of lowTKI (imatinib 300 mg, dasatinib 50 mg or nilotinib 300 mg daily). Asciminib monotherapy demonstrated rapid early and deep molecular responses in patients with CP-CML, with a favorable safety profile. Further data will be presented for patients who added lowTKI."

Clinical • Chronic Myeloid Leukemia • CNS Disorders • Dermatology • Hypertension • Insomnia • Musculoskeletal Pain • Neutropenia • Pancreatitis • Sleep Disorder • Thrombocytopenia • ABL1

A case of delayed transformation to lymphoid blast crisis in a patient with chronic myeloid leukemia (ASH 2025) - "She was transitioned to nilotinib, followed by dasatinib due to cardiac side effects...Although this patient experienced resistance to imatinib early in her course and required three different TKI therapies, she had a major molecular response on dasatinib for over 10 years...Furthermore, the rate of transformation from CML to ALL is much less frequent than transformation from CML to AML, with the risk of transformation dramatically declining after 5 years of starting TKI therapy. This case highlights how a rare CML patient with an MMR may still go on to blast phase disease."

Clinical • Acute Lymphocytic Leukemia • Acute Myelogenous Leukemia • B Acute Lymphoblastic Leukemia • Chronic Myeloid Leukemia • Hematological Malignancies • Leukemia • ABL1 • BCR • CD20 • CD34 • CD79A • MME

Chronic myeloid leukemia and ASXL1 mutations: A distinct entity requiring special attention (ASH 2025) - "Initial treatment: nilotinib 800 mg/day, reduced to 200 mg BID due to hematologic toxicity...Started 7+3 (cytarabine + daunorubicin) + ponatinib on 05/20/2025...NGS:WT1 p.C29_L30insCRHPGPEPRSVC* VAF 1.39%, ASXL1 p.G645Vfs*58 VAF 1.55%, ASXL1 p.E929G VAF 1.46% ,ASXL1 p.T936= VAF 1.41%(Tier 1) Started R-HyperCVAD + dasatinib...In the current era of CML targeted therapy with TKIs or myristoyl inhibitors, the presence of associated genetic alterations (AGAs) becomes relevant, as they may predict aggressive behavior and open a window to evaluate transplantation in these patients for better therapeutic responses. Imatinib is not benefical in this patients."

Chronic Myeloid Leukemia • CNS Disorders • Hematological Disorders • Hematological Malignancies • Hepatology • Herpes Zoster • Infectious Disease • Leukemia • Liver Failure • Musculoskeletal Pain • Myeloproliferative Neoplasm • Respiratory Diseases • Varicella Zoster • ABL1 • ASXL1 • CD20 • CEBPA • GATA2 • WT1

Impact of tyrosine kinase inhibitors on estimated glomerular filtration rate in chronic myeloid leukemia patients (ASH 2025) - "Conclusion Renal function remained stable in most CML patients on TKIs. However, dasatinib was associated with a significant eGFR decline, whereas imatinib and nilotinib showed no such effect."

Clinical • Acute Kidney Injury • Chronic Kidney Disease • Chronic Myeloid Leukemia • Hematological Malignancies • Leukemia • Nephrology • Renal Disease

Treatment-free remission in patients with chronic myeloid leukemia following the second discontinuation of tyrosine kinase inhibitors (ASH 2025) - "Treatment before first discontinuation was imatinib in 58.9% (n=23), nilotinib in 30.8% (n=12), and dasatinib in 10.3% (n=4). All 39 patients were alive at the final follow-up. Conclusion These results demonstrate that a second TKI stop is feasible and the majority of patients regain DMR within 6 months."

Clinical • Chronic Myeloid Leukemia • Hematological Malignancies • Leukemia • TFRC

Chemotherapy free ponatinib + asciminib achieves optimal disease controlpreallohsct in advanced – CML (ASH 2025) - "Pt1: Male, CML diagnosed at age 21; prior TKIs: imatinib, dasatinib, bosutinib; progressed to CML-BC at age 26; no response to ponatinib in monotherapy after two months so asciminib was added for 1 months of combination therapy. The distinct yet complementary mechanisms of TKIs were well tolerated in pt 1 and 2; its use in patients older than 50 years could require caution moreover if precedently treated with nilotinib. These preliminary results warrant further confirmation in larger prospective trials."

Metastases • Chronic Myeloid Leukemia • Myocardial Infarction • ABL1

First report of real-word outcomes of chronic myeloid leukemia in Uruguay in tyrosine kinase inhibitor era (ASH 2025) - "No patient received nilotinib or bosutinib in 1L...Imatinib had the highest frequency of events (39.7%, mostly GI), followed by dasatinib (29.3%, mostly pleural effusion), and nilotinib (16.5%, mostly thrombocytopenia)...Although the disease follow-up could be biased, imatinib outcomes as 1L treatment was inferior to international reports, which suggest it can be improved with second generation TKI use in 1L, but cost and access could be an issue. OS are acceptable and similar to other reports, with significant differences according to known factors such as age, phase and risk."

Chronic Myeloid Leukemia • Hematological Disorders • Hematological Malignancies • Infectious Disease • Leukemia • Respiratory Diseases • Solid Tumor • Thrombocytopenia

Efficacy and safety of pegylated interferon alfa-2b combined with tyrosine kinase inhibitors in chronic Phase chronic myeloid leukemia patients with TKI resistance or intolerance (ASH 2025) - "Median follow-up was 72 weeks (range 24-96).Prior TKIs included imatinib, nilotinib, dasatinib, flumatinib,and olverembatinib.By June 30,2025.Sixteen, fourteen, ten, and eight patients completed therapy at weeks 24,48,72,and 96,respectively.Nine patients discontinued treatment due to adverse events.Molecular responses:Week 24: MMR 37.5% (6/16),DMR 6.3%(1/16),Week 48:MMR57.1% (8/14); Week 72: MMR40.0% (4/10); DMR 30.0% (3/10); Week 96: MMR 50.0% (4/8),DMR 25.0% (2/8).Safety:The most common AEs were flu-like symptoms and hematologic toxicities (predominantly grade 1-2).Dose reductions or extended dosing intervals (up to q2 weeks) of PEG IFNα-2b were implemented to manage AEs. Conclusion PEG IFNα-2b combined with TKIs significantly reduces BCR::ABL1 transcript levels, enabling patients with TKI-resistant or intolerant chronic-phase chronic myeloid leukemia (CP-CML) to achieve major molecular response (MMR) and even deep molecular response (DMR), with a favorable safety..."

Clinical • Chronic Myeloid Leukemia • Hematological Malignancies • Leukemia • ABL1 • IFNA1

Feasibility of the edmonton symptom assessment system (ESAS) score as patient-reported outcomes (PROs) assessment in chronic myeloid leukemia patients receiving tyrosine kinase inhibitor therapy: A pilot Study (ASH 2025) - "TKIs most frequently used before discontinuation were dasatinib (n=8 out of 27 pts, 30%), bosutinib (n=3/8, 37%), imatinib (n=3/5, 60%), nilotinib (n=2/6, 33%), and asciminib (n=2/27, 7%). Additionally, ESAS may be valuable for longitudinal follow-up to assess symptom evolution after treatment changes. Prospective studies with larger cohorts are warranted to validate these observations and determine whether symptom-guided strategies can improve TKI adherence and clinical outcomes in CML."

Clinical • Patient reported outcomes • Anorexia • Chronic Myeloid Leukemia • CNS Disorders • Depression • Hematological Malignancies • Leukemia • Mood Disorders • Palliative care

Treatment free remission after asciminib (ABL001) based therapy in chronic Phase chronic myeloid leukemia (CP-CML) patients who relapsed after a prior attempt at TKI discontinuation-h jean khoury cure CML consortium study HJKC3-0003 (ASH 2025) - "This trial will use any of the following (based on patient/physician preference) during the consolidation treatment phase: asciminib 40 mg PO daily plus imatinib (maximum dose of 400 mg PO once daily), asciminib 40 mg PO bid plus nilotinib (maximum dose of 300 mg bid), asciminib 80 mg PO daily plus dasatinib (maximum dose of 100 mg daily), asciminib 80 mg PO daily. This is the first report of asciminib use to attempt 2 nd TFR. The combination was well tolerated, and patients were able to complete the combination phase. Preliminary results suggest feasibility and potential to increase cure for CML."

Clinical • Chronic Myeloid Leukemia • Hematological Malignancies • Leukemia

Mortality trends in chronic myeloid leukemia in the United States: A population-based analysis (ASH 2025) - "Discussion The substantial reduction in CML mortality over the past two decades aligns with the widespread adoption of TKIs, particularly imatinib (approved 2001). The subsequent approval of dasatinib (2006), nilotinib (2007), and bosutinib (2012) has aided in the transformation of CML from a fatal disease to a chronic condition for most patients...Males and White individuals face higher apparent mortality rates. The slight uptick in mortality from 2018 to 2020 may be related to the increased vulnerability of patients with hematologic malignancies to severe COVID-19 infection."

Clinical • Chronic Myeloid Leukemia • Hematological Malignancies • Infectious Disease • Leukemia • Novel Coronavirus Disease • ABL1 • BCR

Comparative 3- and 5-year outcomes among first-line imatinib, dasatinib, and nilotinib in chronic myeloid leukemia: A real world analysis (ASH 2025) - "Imatinib showed the most favorable survival at 3 and 5 years. Dasatinib was associated with higher mortality but lower diabetes risk, while nilotinib offered similar survival and a trend toward reduced hospitalizations. These results support personalized TKI selection in frontline CML therapy."

Clinical • Real-world • Real-world evidence • Chronic Myeloid Leukemia • Coronary Artery Disease • Diabetes • Hematological Malignancies • Hypertension • Leukemia • Metabolic Disorders

Efficacy of novel agents in the treatment of acute myeloid leukemia and myelodysplastic syndrome: A systematic review and meta-analysis (ASH 2025) - "Newer agents included for AML were Guadectiabine, Magrolimab, Alvocidib, Enasidenib, Flotetuzumab, Vadastuximab, Mitoxantrone, Pevonedistat, Entospletinib, Eprenetapopt, Belinostat, Onvansertib, Panobinostat, Cediranib Maleate, Nilotinib, Emavusertib, and anti-CD45 antibody (DOTA-BC8). The newer agents investigated for MDS included Rigosertib, Imetelstat, Pembrolizumab, Enasidenib, Sabatolimab, Ivosidenib, Elitercept, Pevonedistat, Emavusertib, Atezolizumab, and Olutasidenib...All patients were treated concomitantly with either azacitidine (77%) or decitabine (23%)... This meta-analysis and systematic review demonstrate promising efficacy for novel agents in AML and MDS patients. There is a need for prospective trials with larger patient populations to investigate these agents further."

Retrospective data • Review • Acute Myelogenous Leukemia • Hematological Disorders • Hematological Malignancies • Leukemia • Myelodysplastic Syndrome • Neutropenia • TP53

Second-generation tyrosine kinase inhibitors vs imatinib in adult ph+ ALL: Target-trial emulation using a propensity-matched multinational cohort (ASH 2025) - "Second-generation BCR-ABL1 tyrosine-kinase inhibitors (2G-TKIs; dasatinib, nilotinib, bosutinib) achieve deeper kinase inhibition and superior central-nervous-system penetration, yet their incremental benefit over imatinib in modern adult practice remains uncertain because head-to-head phase-3 trials are lacking. Frontline second-generation BCR-ABL1 TKIs, predominantly dasatinib, deliver a clinically meaningful five-year survival advantage over imatinib in real-world adult Ph+ ALL without increasing treatment-related mortality. The benefit is concentrated in adults older than 35 years, whereas estimates in 18–35 years are not significant, supporting age-informed TKI selection. Transplant use and CNS relapse are similar between groups, and falsification outcomes are neutral, strengthening causal confidence."

Clinical • Acute Lymphocytic Leukemia • Diabetes • Gastroenterology • Gout • Hematological Disorders • Hematological Malignancies • Inflammatory Arthritis • Leukemia • Nephrology • Renal Calculi • Rheumatology • Thrombocytopenia • ABL1 • BCR

Cholesterol and lipid-associated transcriptional signature in chronic myeloid leukemia patients with nilotinib-induced hypercholesterolemia (ASH 2025) - "2022).To the best of our knowledge, this is the first enrichment-based signature with potential utility for CML patient stratification. Future studies involving larger cohorts and refined gene panels may improve its predictive value and guide personalized therapeutic approaches."

Clinical • Atherosclerosis • Chronic Myeloid Leukemia • Coronary Artery Disease • Dyslipidemia • Hematological Malignancies • Leukemia • Metabolic Disorders • APOB • CAMK2D • CD34 • CD36 • CDC37 • HSP90AA1 • HSP90AB1 • LYN • RAC1 • SCARB1 • VDAC3

Real-world treatment patterns, outcomes, and unmet needs in patients with ph+ ALL receiving tyrosine kinase inhibitors in the United States: Emerging trends and the role of asciminib-based combinations (ASH 2025) - "Anytime during the follow-up period, 67%received dasatinib, 35% ponatinib, 24% imatinib, 13% nilotinib, 6% bosutinib, and 66 (2%) asciminib-based therapy.Based on the index TKI, treatment patterns evolved over time, with important shifts between 2016 and2024...Asciminib was given ascombination therapy (82%) with corticosteroids (76%), chemotherapy (64%), inotuzumab ozogamicin(16%), and blinatumomab (15%). This real-world study described evolving patterns in the management of pts with Ph+ ALL... This real-world study described evolving patterns in the management of pts with Ph+ ALL. Inrecent years, increased use of ponatinib and immunotherapy has been observed alongside a decline inuse of dasatinib and imatinib. Despite therapeutic advances, many pts experienced clinical eventsassociated with TKI-related conditions, and one-third had disease relapse."

Clinical • HEOR • Real-world • Real-world evidence • Acute Lymphocytic Leukemia • Constipation • Gastroenterology • Gastrointestinal Disorder • Hematological Malignancies • Ischemic stroke • Leukemia • Myocardial Infarction • Respiratory Diseases

Discontinuation of tyrosine kinase inhibitors in chronic myeloid leukemia. a randomized national fi-LMC comparative trial of two therapeutic strategies. (ASH 2025) - P3 | "Minimum TKI doses required foreligibility are: imatinib (≥ 300 mg/day), dasatinib (≥ 50 mg/day), nilotinib (≥ 300 mg/day), and bosutinib (≥200 mg/day). Finally, this trial offers aunique opportunity to explore the hypothesis of an inverse correlation between the number andfunction of anti-leukemic effector cells and the plasma TKI levels.ConclusionsWe aim to demonstrate that de-escalation of TKI therapy improves the proportion of patients who cansuccessfully discontinue treatment, thus maintaining a stable MR4 and achieving prolonged TFR. We alsoseek to provide evidence that this benefit is supported by the immune system effectors, particularly byinnate T cells."

Clinical • Chronic Myeloid Leukemia • Hematological Malignancies • Leukemia • ABL1

Asciminib and pregnancy in CML: Preliminary human data and clinical implications from 47 reported outcomes (ASH 2025) - "In the paternal exposure group, 8 men were receiving ASC asmonotherapy at the time of conception, while 5 were treated with ASC in combination with nilotinib orimatinib...In most cases, ASC hadbeen discontinued during the first trimester, often between 4 and 9W, with daily doses ranging from 20to 120 mg, and one ASC 40 QD+imatinib 400 mg...However, contraception is advised for women on ASC, especially if previouslyfailing other treatments; no contraception is needed for men. The presentation will provide updatedclinical details, including CML management during gestation and reproductive outcomes, offeringinsights to improve patient counseling, support informed reproductive choices, and guide personalizedtreatment."

Clinical • Chronic Myeloid Leukemia • Hematological Malignancies • Infectious Disease • Leukemia • Pneumonia • Respiratory Diseases • ABL1

Outcomes of patients with chronic myeloid leukemia receiving second-line therapy after failure of frontline second-generation tyrosine kinase inhibitor (ASH 2025) - "The 10-year EFS, TFS, and OS rates with 1L were 57%, 100%,and 79%, respectively.2L consisted of imatinib in 74 pts (27%), bosutinib in 64 (23%), nilotinib in 57 (21%), dasatinib in 43 (15%),ponatinib in 31 (11%), asciminib in 6 (2%), and investigational drug in 1 (1%). Of 65 pts withtranscripts <0.1%, 59 (91%) maintained their response.The estimated 10-year EFS, TFS, and OS rates on 2L therapy were 67%, 87%, and 71%, respectively.ConclusionOverall, 2L after 1L 2G-TKI resulted in cytogenetic remissions in approximately 80% of the pts andmolecular remissions in more than 60% of the pts. Response rates were significantly higher in pts treatedwith a 3G-TKI compared to a 2G-TKI in the second line."

Clinical • Chronic Myeloid Leukemia • Hematological Malignancies • Leukemia • ABL1

Clinical and molecular features associated with glucolipid metabolic disorders and cardio-/cerebro-vascular adverse events in CML patients receiving olverembatinib therapy (ASH 2025) - "22 (13%) patients experienced imatinib failure only; 50 (30%), imatinib,dasatinib and/or flumatinib therapy failure; and 95 (57%) had a history of nilotinib exposure. Higher total cholesterol, more priorTKI-therapy lines, particularly prior nilotinib exposure, the presence of ASXL1, FAT4 and/or TET2mutations were the independent predictors for glucolipid metabolic disorders, CCVAEs andarterial/venous occlusive events. These clinical and molecular features may guide early risk identificationand targeted surveillance."

Adverse events • Clinical • Cerebral Hemorrhage • Chronic Myeloid Leukemia • Congestive Heart Failure • Diabetes • Dyslipidemia • Heart Failure • Hematological Disorders • Hematological Malignancies • Hypertension • Leukemia • Metabolic Disorders • Pulmonary Arterial Hypertension • Pulmonary Disease • Respiratory Diseases • ABL1 • ASXL1 • FAT4 • TET2

Intronic DNA variants in EZH2 and GATA2 predict treatment-free remission in chronic myeloid leukemia patients from the destiny trial (ASH 2025) - P2 | "The DESTINY trial(NCT01804985) enrolled CML patients in stable deep molecular remission (DMR; BCR::ABL1:ABL1<0.01%IS) or major molecular response (MMR; BCR::ABL1:ABL1 <0.1%IS) following ≥3 years treatment withimatinib, nilotinib or dasatinib, for TKI discontinuation. Using BM MNCs from patients in the DESTINY trial, we found that intronic variants in EZH2and GATA2 were positively associated with sustained TFR, while DNMT3A variants were associated withrecurrence. Together, these findings support targeted investigation into the genomic and molecularmechanisms underpinning BCR::ABL1 clonal escape after TKI withdrawal. Furthermore, this studysupports a strong rationale to validate targeted NGS as a means of risk stratifying CML patients who areeligible for TKI discontinuation."

Clinical • Chronic Myeloid Leukemia • Hematological Disorders • Hematological Malignancies • Leukemia • ABL1 • BCOR • DNMT3A • GATA2 • SH2B3

High rates of deep molecular response (DMR) in patients (pts) with chronic myeloid leukemia in chronic Phase (CML-CP) who have not achieved dmr after ≥1 year of prior imatinib (IMA) in the asciminib (ASC) monotherapy arm of the Phase 2 ASC4MORE study (ASH 2025) - P2 | "In the phase 2ASC2ESCALATE study (NCT05384587), second-line ASC demonstrated high molecular response rates anda favorable safety profile, consistent with established ASC data across tx lines.The ASC4MORE study (NCT03578367) initially compared ASC 40 or 60 mg once daily (QD) add-on to IMA400 mg QD vs continued IMA 400 mg QD vs switch to nilotinib (NIL) 300 mg twice daily in pts with CML-CPnot achieving MR4 with ≥1 year of 1L IMA. No new or worsening safety signalswere observed compared with prior ASC studies and overall QOL improved or remained stable in mostpts. Results support early switching to ASC as an effective strategy to achieve DMR while maintainingfavorable safety/tolerability and QOL."

Clinical • Monotherapy • P2 data • Anorexia • Cardiovascular • Chronic Myeloid Leukemia • CNS Disorders • Constipation • Gastroenterology • Gastrointestinal Disorder • Hematological Malignancies • Hypertension • Infectious Disease • Insomnia • Leukemia • Musculoskeletal Pain • Nephrology • Pancreatitis • Pulmonary Disease • Sleep Disorder