bosutinib / Generic mfg. - 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

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

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

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

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

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 for newly diagnosed chronic myeloid leukemia: Results from A phase II trial (ASH 2025) - "A 71-year-oldpatient with a previous medical history of hypertension developed G5 acute coronary syndrome after 2.5months of asciminib therapy.Overall, 5 of 50 patients (10%) discontinued asciminib after a median of 7.6 months (range, 0.5-16.6) dueto 1) a G3 subacute brain stroke, switched to bosutinib; 2) a G2 and G3 pancreatitis in one patient each,both switched to dasatinib; 3) a G5 acute coronary syndrome (NSTEMI) with cardiogenic shock in a 71-year-old male w; 4) a loss of CCyR after 11.4 months of therapy with the emergence of A337T and F497Lmutations with subsequent switch to ponatinib. The 6-month rates of FFS, EFS, and OS were 93%, 97%,and 97%, respectively.ConclusionThis interim analysis showed very good response rates with asciminib in ND CML after a short follow-upwith MMR and deep molecular response rates of 64% and 42% by 6 months, respectively. Adverseevents, including gastrointestinal, as well as one fatal cardiovascular event, were observed."

P2 data • Acute Coronary Syndrome • Chronic Myeloid Leukemia • Coronary Artery Disease • Hematological Malignancies • Hypertension • Leukemia • Musculoskeletal Pain • Pancreatitis • 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

Predictive factors for successful treatment-free remission in patients with chronic myeloid leukemia: A pooled analysis (ASH 2025) - "First-line TKI was imatinib in196 pts (48%), nilotinib in 100 (24%), dasatinib in 93 (23%), ponatinib in 16 (4%), and bosutinib in 4 (1%).309 pts electively discontinued TKI (76%), 72 (18%) discontinued therapy due to adverse events, 7 (2%) forpregnancy, 7 (2%) for financial reasons, 6 (1%) due to the diagnosis of another malignancy, and 6 (1%) forother reasons. ConclusionTreatment DC is a safe approach in pts with CML who achieve a prolonged DMR, with no increase in therisk of disease progression or CML-related deaths. A sustained duration of DMR of more than 5 years wasassociated with the highest rates of MRFS and TFR."

Biomarker • Retrospective data • Chronic Myeloid Leukemia • Hematological Malignancies • Leukemia • ABL1

Improved long-term tolerability with asciminib (ASC) vs investigator-selected (IS) tyrosine kinase inhibitors (TKIs) in patients (pts) with newly diagnosed chronic myeloid leukemia in chronic phase (CML-CP): Week 96 exploratory analysis of the phase 3 ASC4FIRST trial (ASH 2025) - P3 | "Wereport exploratory post hoc analyses, including an innovative analysis of AE-free days, further evaluatingthe tolerability of ASC vs IS-TKI (imatinib [IMA]/2G TKIs) by the wk 96 analysis cutoff (Oct 22, 2024).MethodsAdults with newly diagnosed CML-CP were randomized 1:1 to receive ASC or IS-TKI (at label dose),stratified by ELTS risk category and prerandomization IS-TKI (IMA/2G TKIs)...Dose adjustment and/or interruption due to grade ≥3 nonhematologic AEs occurred in17.0% vs 8.1% of pts with ASCIMA vs IS-TKIIMA and 11.0% vs 17.6% with ASC2G vs IS-TKI2G.Pts with ASC vs IS-TKIs had a higher median percentage of AE-free days by wk 96 (ASCIMA [15.7%] vs IS-TKIIMA [3.5%]; ASC2G [22.6%] vs IS-TKI2G [4.3%]) and vs individual 2G TKIs (nilotinib [13.5%]; dasatinib[4.2%]; bosutinib [0.1%]) in this arm...Effective relative dose intensity (>90%) was higher with ASC vs IS-TKIs, with generally fewer ptsrequiring dose reduction, interruption, or discontinuation. These results..."

Clinical • P3 data • Chronic Myeloid Leukemia • Infectious Disease • Novel Coronavirus Disease • Respiratory Diseases

Beyond survival in chronic myeloid leukemia: A systematic review of secondary malignancies in the era of tyrosine kinase inhibitors (ASH 2025) - "Eligible studies were those reporting the incidence of SMs in adults withchronic-phase CML treated with TKIs, including imatinib, dasatinib, nilotinib, bosutinib, ponatinib, andasciminib...Data on bosutinib (n=2) and ponatinib (n=1) were limited, while asciminib was notreported in any study... This reviewidentified a notable incidence of SMs, particularly involving prostate, colorectal, lung, and lymphoidcancers. While some variability in cancer types was observed across studies, no consistent associationcould be established between TKI generation or treatment duration and SMs risk.SM development wasassociated with poor prognosis and increased mortality, highlighting the need for proactive surveillance.Large-scale prospective studies are needed to clarify causality, define long-term safety, and informsurvivorship strategies."

Review • Breast Cancer • Chronic Myeloid Leukemia • Colorectal Cancer • Hematological Malignancies • Leukemia • Lymphoma • Non-Hodgkin’s Lymphoma • Oncology • Solid Tumor

Reattempt of tyrosine kinase inhibitor discontinuation after maintenance therapy with ponatinib in patients with chronic myeloid leukemia in the chronic phase: Result of JALSG CML RE-STOP219 study. (ASH 2025) - "The TKIs that were discontinued first were dasatinib (39.0%), nilotinib(36.6%), imatinib (14.6%) and bosutinib (9.8%). This study suggests that a second TKI discontinuation following ponatinib maintenancetherapy may confer the benefit of successful TFR in certain patients. Notably, patients who initiallydiscontinued imatinib showed a higher TFR rate. Additionally, long-term treatment history and longer TFRduration during the initial TKI discontinuation correlated with a higher TFR rate."

Clinical • Bone Marrow Transplantation • Chronic Myeloid Leukemia • Hematological Malignancies • Leukemia • ABL1

Dosing variability of tyrosine kinase inhibitors in chronic myeloid leukemia (ASH 2025) - "The latest TKI therapy included dasatinib, imatinib, bosutinib, nilotinib, asciminib andponatinib in 34%, 29%, 18%, 11%, 6% and 2% of the patients, respectively. Most importantly, we note that more than 50% of the patientsare on a lower dose TKI in the later line settings without compromising outcomes, highlighting that thereis room for optimization of TKI dosing strategy in CP-CML for improved patient tolerance whilemaintaining outcomes. Larger registry studies are needed to better understand prescription practices ofTKIs in CP-CML."

Chronic Myeloid Leukemia • Hematological Malignancies • Leukemia

The humanistic burden of patients with chronic myeloid leukemia (CML) treated with first line (1L) tyrosine kinase inhibitors (TKIs) (ASH 2025) - "Adultsreceiving 1L TKIs (imatinib, dasatinib, nilotinib, bosutinib) for ≥3 months (mos) were eligible to participate; asciminib in 1L was not yet approved at study start. Our real-world study demonstrates pts with CML treated with 1L TKIs in the US experience chronic AEscontributing to worse HRQoL, including physical and mental health, as well as work impairment. Thisfinding of impaired work productivity due to CML is particularly significant in the context of employer-provided health insurance in the US. While most patients discussed AEs with physicians early in theirdisease course, only half discussed AEs at every visit and two-thirds were satisfied with their discussions.In addition, some patients delayed or avoided reporting AEs due to internal barriers."

Clinical • Chronic Myeloid Leukemia • Constipation • Gastroenterology • Gastrointestinal Disorder • Hematological Malignancies • Leukemia • Musculoskeletal Pain

Asciminib (ASC) in chronic myeloid leukemia in chronic Phase (CML-CP): Efficacy and safety results of the Phase 2 ASC2ESCALATE trial in the cohort of patients (pts) with 1 prior tyrosine kinase inhibitor (TKI) (ASH 2025) - P2 | "Prior TKIs included dasatinib (44.6%), imatinib (42.6%),nilotinib (9.9%), or bosutinib (5.0%). The impact of dose escalation in pts not meeting responsemilestones continues to be explored. All 101 pts will be evaluated for safety and efficacy in the primarywk 48 analysis, which will be presented at ASH2025."

Clinical • P2 data • Cardiovascular • Chronic Myeloid Leukemia • CNS Disorders • Dyspepsia • Hematological Disorders • Hematological Malignancies • Hypertension • Leukemia • Movement Disorders • Neutropenia • Thrombocytopenia

Management and outcomes of patients diagnosed with chronic myeloid leukemia in blast Phase: A multicenter analysis by the h jean khoury cure CML consortium (ASH 2025) - "Dasatinib(n=99; 34.9%) and ponatinib (n=97; 34.3%) were the most used TKIs followed by imatinib (n=23; 8.1%),nilotinib (n=21; 7.4%), bosutinib (n=8; 2.8%) and asciminib (n=3; 1.1%). CML-BP continues to have poor prognosis. Treatment is heterogenous involving various combinations ofTKI and chemo. In our analysis, treatment with 2G-TKI or ponatinib led to better responses."

Clinical • Chronic Myeloid Leukemia • Hematological Malignancies • Leukemia • Sarcoma • Solid Tumor • ABL1 • ASXL1 • BCOR • BCORL1 • BCR • DNMT3A • RUNX1

CARDINAL: A Phase 1 study of TERN-701, a novel investigational allosteric BCR::ABL1 inhibitor for patients with previously treated CML (ASH 2025) - P1 | "Herewe report initial results from the ongoing Phase 1 study of TERN-701 in pts with previously treated CML-CP. CARDINAL (NCT06163430) is an ongoing, open-label, two-part, global, multicenter Phase 1study in pts ≥18 years old with BCR::ABL1-positive CML-CP (with or without T315I mutation and withoutmyristoyl binding pocket mutations) previously treated with ≥1 prior second-generation (2G) TKI(bosutinib, dasatinib, or nilotinib)...Baseline characteristics included: median 3 prior TKIs (range: 1‒6); 35% had ≥4 prior TKIs; 36% had prior asciminib; 25% had prior ponatinib and/or investigational TKI(olverembatinib/ELVN-001); 56% had baseline BCR::ABL1>1%, with 44% having baseline BCR::ABL1>10%; and 13% with BCR::ABL1 mutations (9% T315I, 4% F317L)... TERN-701 demonstrated encouraging safety/tolerability and efficacy in a heavily pre-treatedpatient population with CML-CP previously treated with approved 1G/2G TKIs, ponatinib, asciminib, andother investigational,..."

Clinical • P1 data • Chronic Myeloid Leukemia • Hematological Disorders • Hematological Malignancies • Leukemia • Neutropenia • Thrombocytopenia

The impact of patient personality traits on adherence to tyrosine kinase inhibitor therapy in patients with chronic myeloid leukemia (ASH 2025) - "Eligible patients were adults (18years of age and older) with chronic-phase CML on one of six FDA-approved TKIs: imatinib, dasatinib,bosutinib, nilotinib, ponatinib, or asciminib. Specifically, patientsexhibiting high neuroticism may benefit from interventions targeting emotional regulation and stresscoping to improve adherence and, ultimately, clinical outcomes. Future studies in larger cohorts arewarranted to validate these findings and to further explore how personality-driven, personalizedmedicine approaches may enhance long-term treatment success in CML."

Adherence • Clinical • Chronic Myeloid Leukemia • Hematological Malignancies • Leukemia • Mood Disorders • Myeloproliferative Neoplasm • ABL1

Association of socioeconomic indicators with survival in chronic myeloid leukemia: A retrospective analysis (ASH 2025) - "First-line TKIs were imatinib (n=183, 53%), dasatinib (n=105, 30%), nilotinib (n=51, 15%) &bosutinib (n=8, 2%). The availability of patientassistance programs may have mitigated poor outcomes in pts who are uninsured or have financialdifficulties. Our study findings highlight the complex and sometimes partial impact of SEI on long-termoutcomes in CML."

Retrospective data • Chronic Myeloid Leukemia • Hematological Malignancies • Leukemia

Major adverse cardiovascular events (MACE) in patients with chronic myeloid leukemia treated with tyrosine kinase inhibitors: A target trial emulation study (ASH 2025) - "The primary trial compared imatinib topooled second/third-generation TKIs (bosutinib, dasatinib, nilotinib, ponatinib); to account for treatmentswitching, secondary trials compared imatinib to each agent individually. In this large real-world target trial emulation, second- and third-generation TKIs were associated withsignificantly higher risk of MACE and mortality compared to imatinib. Among individual agents, nilotiniband dasatinib demonstrated the highest cardiovascular risks, while bosutinib showed trends towardincreased risk without reaching statistical significance after correction. These findings highlight theimportance of cardiovascular risk stratification when selecting TKIs and underscore the need for vigilantlong-term cardiovascular monitoring, referral and evaluation by a cardio-oncologist."

Adverse events • Clinical • Acute Coronary Syndrome • Chronic Myeloid Leukemia • Congestive Heart Failure • Heart Failure • Hematological Malignancies • Hepatology • Human Immunodeficiency Virus • Infectious Disease • Leukemia • Liver Failure • Myocardial Infarction

A randomized study of ropeginterferon in combination with bosutinib in newly diagnosed chronic myeloid leukemia (CML) patients in chronic Phase. the bosupeg trial from the Nordic CML study group (ASH 2025) - "Introduction: Prior studies combining pegylated interferon-α to Imatinib and Nilotinib in newly diagnosedCML patients have indicated an additive effect with faster and deeper molecular responses (SPIRIT,TIGER, NordCML002, NiloPEG). In this trial we used a bosutinib (BOS) backbone combined with low-doseropeginterferon alfa-2b (BESREMi, AOP Health), which in contrast to previously tested interferons has alonger half-life and a more favorable tolerability profile...Most switched patients received 1st and 2nd generation TKIs, butsome were transplanted or received ponatinib... The step-up dosing strategy for BOS reduced GI toxicity, but not transaminitis. Efficacy wasexcellent in comparison with the registration study (BFORE). The combination of ropeginterferon andBOS was safe and efficacious."

Clinical • Combination therapy • Chronic Myeloid Leukemia • CNS Disorders • Hematological Malignancies • Immunology • Infectious Disease • Leukemia • Mental Retardation

Preliminary safety and efficacy of ELVN-001, a selective active site inhibitor of BCR::ABL1, in patients with CML driven by atypical fusion transcripts (ASH 2025) - P1 | "Thepatient discontinued prior imatinib and nilotinib due to lack of efficacy, had a concurrent diagnosis ofMDS (treated with dasatinib plus azacitidine), a prior allogeneic myeloablative stem cell transplant, andwas last treated with asciminib (discontinued due to lack of efficacy)...The patient discontinued prior nilotinib, dasatinib,ponatinib, asciminib and a combination of asciminib and ponatinib due to lack of efficacy...ELVN-001 demonstrated encouraging anti-CML activity in patients with atypical transcripts, including inpatients with the e13a3 transcript, which is resistant to TKIs targeting the myristoyl pocket."

Clinical • Chronic Myeloid Leukemia • ABL1