bosutinib / Generic mfg. - LARVOL DELTA

Impact of Posterior Reversible Encephalopathy Syndrome on Hospitalization and Mortality in Tyrosine Kinase Inhibitor-Treated Patients With Hematologic Malignancies: A Real-World Propensity-Matched Analysis (SOHO 2026) - " Using the TriNetX Global Collaborative Network (170 healthcare organizations), we identified TKI-treated patients (imatinib, dasatinib, bosutinib, ibrutinib, or erlotinib) who developed PRES within 1 year of initiation (cohort 1, n = 135) vs TKI-treated controls without PRES (cohort 2, n = 69764), excluding those with cocaine use disorders or hypertensive urgency/emergency. TKI-treated patients, including those receiving CML-directed BCR-ABL1 inhibitors, who developed PRES faced a nearly 2-fold increased hazard of hospitalization (HR, 1.799) and nearly 3-fold increased hazard of death (HR, 2.683) compared to propensity-matched controls, with median survival reduced to 1758 days versus not reached. PRES should be recognized as a high-stakes complication rather than a transient neurological event. Given the markedly shortened time to first hospitalization (190 vs 1404 days), early vigilance for PRES in TKI-treated patients is warranted."

Clinical • Real-world • Real-world evidence • Chronic Myeloid Leukemia • Hematological Malignancies • Leukemia • Oncology • BCR

Efficacy and Safety of Asciminib in Chronic Myeloid Leukemia in Chronic Phase (CML-CP): Interim Results from the Phase 2 ASC2ESCALATE Trial in the Cohort of Patients (Pts) after 1 Prior Tyrosine Kinase Inhibitor (TKI) (ASH 2024) - P2 | "Pts had received prior treatment with imatinib (32.6%), dasatinib (48.8%), nilotinib (16.3%), or bosutinib (2.3%); 76.7% had received their prior TKI for ≥12 mo. These promising results support asciminib as a potential treatment option in these pts. Updated data (data cutoff June 28, 2024) will be presented at the ASH 2024 Annual Meeting."

Clinical • P2 data • Cardiovascular • Chronic Myeloid Leukemia • Cough • Fatigue • Hematological Malignancies • Hypertension • Leukemia • Oncology • Respiratory Diseases

Bosutinib versus imatinib for newly diagnosed chronic phase chronic myeloid leukemia: final results from the BFORE trial. (PubMed, Leukemia) - P3 | "After 5 years of follow-up there was an increase in the incidence of cardiac, effusion, renal, and vascular TEAEs in bosutinib- and imatinib-treated patients, but overall, no new safety signals were identified. These final results support 400-mg once-daily bosutinib as standard-of-care in patients with newly diagnosed CP CML.This trial was registered at www.clinicaltrials.gov as #NCT02130557."

Journal • Chronic Myeloid Leukemia • Hematological Malignancies • Leukemia • Oncology

ASCIMINIB (ASC) PROVIDES SUPERIOR EFFICACY AND EXCELLENT SAFETY AND TOLERABILITY VS TYROSINE KINASE INHIBITORS (TKI) IN NEWLY DIAGNOSED CHRONIC MYELOID LEUKEMIA (CML) IN THE PIVOTAL ASC4FIRST STUDY (EHA 2024) - P3 | "ASC, the first BCR::ABL1 inhibitor to Specifically Target theABL Myristoyl Pocket (STAMP), was intentionally designed to be highly specific and minimize off-target effects.We report primary results from ASC4FIRST (NCT04971226), a randomized ph 3 study of ASC vs all currentstandard-of-care frontline TKIs in pts with newly diagnosed CML.Aims:The two primary objectives were to demonstrate superior major molecular response (MMR) rate at wk 48 withASC vs investigator-selected (IS) TKI and ASC vs IS TKI within the stratum of pts with imatinib (IMA) as theirprerandomization-selected (PRS) TKI (ASCIMA vs IS TKIIMA). Pts received ASC (n=201: ASCIMA, n=101; ASC2G, n=100) or an IS TKI (n=204: IS TKIIMA, n=102; IS TKI2G,n=102 [nilotinib, 48%; dasatinib, 41%; and bosutinib, 11%]). Median follow-up was 16.3 and 15.7 mo with ASCand IS TKIs, respectively. At cutoff (Nov 28, 2023), Tx was ongoing in 86%, 62%, and 75% of pts receiving ASC,IMA, and 2G TKIs, respectively (Figure).MMR..."

Clinical • Anemia • Chronic Myeloid Leukemia • Hematological Disorders • Hematological Malignancies • Leukemia • Neutropenia • Oncology • Thrombocytopenia

Sustained Efficacy and Safety with Asciminib (ASC) after Almost 4 Years of Median Follow-up from Ascembl, a Phase 3 Study of ASC Vs Bosutinib (BOS) in Patients (Pts) with Chronic Myeloid Leukemia in Chronic Phase (CML-CP) after ≥2 Prior Tyrosine Kinase Inhibitors (TKIs): An End of Study Treatment (EOS Tx) Update, Including Results from Switch Population (ASH 2023) - " Adults (aged ≥18 y) with CML-CP after ≥2 prior TKIs, with intolerance or lack of efficacy per 2013 ELN recommendations were randomized 2:1 to receive either ASC 40 mg twice daily or BOS 500 mg once daily. With almost 4 y of follow-up in ASCEMBL, ASC continued to show greater efficacy and better safety/tolerability than BOS in pts with CML-CP after ≥2 prior TKIs. The robust safety profile of ASC was sustained through each analysis in ASCEMBL (wk 24, wk 96, and EOS Tx), confirming that pts receiving ASC can maintain a high level of response and continue Tx without experiencing late-emerging AEs. Results in the switch population support the use of ASC early in the Tx paradigm."

Clinical • P3 data • Chronic Myeloid Leukemia • Hematological Disorders • Hematological Malignancies • Leukemia • Neutropenia • Oncology • Thrombocytopenia

POLARIS-2: Study of Olverembatinib (HQP1351) in Patients With CML-CP (clinicaltrials.gov) - P3 | N=333 | Recruiting | Sponsor: Ascentage Pharma Group Inc. | Trial completion date: Feb 2026 ➔ Jul 2028 | Trial primary completion date: Dec 2025 ➔ Jun 2027

Trial completion date • Trial primary completion date • Chronic Myeloid Leukemia • Hematological Malignancies • Leukemia • Oncology

Atherothrombotic Adverse Effects of Tyrosine Kinase Inhibitors in Patients With Chronic Myeloid Leukemia (SOHO 2026) - " The patients were receiving imatinib (26 patients; 16%), nilotinib (50 patients; 31%), dasatinib (26 patients; 16%), bosutinib (4 patients; 3%), ponatinib (44 patients; 28%), asciminib (7 patients; 6%), and vamotinib (2 patients; 1%). In patients with CML, ATAEs are associated with initially high CV risk. Nilotinib and ponatinib demonstrated the most unfavorable toxicity profiles. These findings highlight the importance of CV risk assessment before TKI initiation and its dynamic monitoring during treatment."

Adverse events • Clinical • Chronic Myeloid Leukemia • Hematological Malignancies • Leukemia • Oncology

Allosteric kinase inhibition in hematological malignancies: from asciminib to emerging regulatory sites. (PubMed, Biochem Pharmacol) - "This review fills that gap with two contributions: mechanistic evidence that crizotinib engages BCR::ABL1 through a putative dual ATP-site/myristoyl-pocket mechanism, supported by indirect evidence and pending direct structural confirmation; and a hypothesis linking recurrent synonymous mutations in non-receptor tyrosine kinases to transiently structured regulatory regions, as a strategy for identifying latent allosteric sites Asciminib is the proof of concept...In the ASCEMBL trial, it achieved a major molecular response rate of 25.5% at 24 weeks versus 13.2% for bosutinib in heavily pretreated CML, with better tolerability-the first regulatory-site inhibitor approved for a hematological malignancy...Asciminib resistance is already real: A337V and P465S mutations reduce binding, and bypass signaling adds another layer. Each approved allosteric agent-asciminib, trametinib, and ivosidenib-required extensive structural and functional validation before reaching the clinic;..."

Journal • Review • Chronic Myeloid Leukemia • Hematological Disorders • Hematological Malignancies • Oncology • ABL1 • FLT3 • JAK2

Efficacy and Safety of Ponatinib as a Second‑Line Treatment for Chronic‑Phase Chronic Myeloid Leukemia: Retrospective Study at Two Japanese Centers. (PubMed, Indian J Hematol Blood Transfus) - "The TKIs administered as first-line treatment were as follows: bosutinib in eight patients (50%), dasatinib in six patients (38%), and nilotinib in two patients (13%). Five patients (31%) discontinued ponatinib. Ponatinib demonstrated high efficacy in treating CML-CP resistant or intolerant to second-generation TKIs."

Journal • Retrospective data • Chronic Myeloid Leukemia • Hematological Malignancies • Leukemia • Oncology

Target Attainment and Clinical and Biochemical Parameters Associated with the Pharmacokinetics of 12 Tyrosine Kinase Inhibitors. (PubMed, Clin Pharmacokinet) - "Target attainment was suboptimal for most TKIs, supporting the need for TDM-guided optimisation and individualised dosing. Associations between TKI exposure and renal, hepatic, and haematological parameters further support personalised treatment strategies."

Journal • PK/PD data • Hematological Disorders • Oncology

ASC4FIRST, a pivotal phase 3 study of asciminib (ASC) vs investigator-selected tyrosine kinase inhibitors (IS TKIs) in newly diagnosed patients (pts) with chronic myeloid leukemia (CML): Primary results. (ASCO 2024) - P3 | " Adults with CML were randomly assigned 1:1 to receive ASC 80 mg once daily or an IS TKI at standard label doses, stratified by ELTS risk category and prerandomization selected (PRS) TKI (imatinib [IMA] or second-generation [2G] TKIs), which was selected by investigators before randomization, accounting for pt preference... Pts received ASC (n=201: ASC IMA , n=101; ASC 2G , n=100) or IS TKI (n=204: IS TKI IMA , n=102; IS TKI 2G , n=102 [nilotinib, 48%; dasatinib, 41%; bosutinib, 11%])... ASC is the only agent to show a statistically significant superior efficacy and excellent safety and tolerability vs all current standard-of-care frontline Tx, with potential to be the therapy of choice for CML."

Clinical • Late-breaking abstract • P3 data • Chronic Myeloid Leukemia • Hematological Malignancies • Leukemia • Oncology • ABL1

Prescription Behaviour and Drug Interactions of Acid Suppressants With Tyrosine Kinase Inhibitors in Patients With Leukaemia: Data From Germany. (PubMed, EJHaem) - "Results indicate substantial co-prescription rates involving dasatinib, nilotinib, imatinib, bosutinib and ponatinib, with variations across years and agents. The findings highlight the need for improved prescriber awareness, adherence to guidelines and risk mitigation strategies such as therapeutic drug monitoring or alternative dosing. Collaborative efforts between clinicians and regulatory bodies are essential to minimize risks and optimize patient outcomes."

Journal • Review • Chronic Myeloid Leukemia • Hematological Malignancies • Leukemia • Oncology

Large-scale pleiotropic analysis across cancers reveals shared genetic mechanisms and identifies novel functional genes. (PubMed, Brief Bioinform) - "Importantly, drug sensitivity assays demonstrated that bosutinib and cobimetinib exhibited promising therapeutic potential in breast cancer cell lines. Finally, we developed the PleioCancer database (https://gonglab.hzau.edu.cn/PleioCancer/), providing a comprehensive resource for cancer pleiotropy research. These findings have important implications for carcinogenesis cancer, prevention and treatment."

Journal • Breast Cancer • Oncology • Solid Tumor • FANCA

Asciminib (ASC) Demonstrates Favorable Safety and Tolerability Compared with Each Investigator-Selected Tyrosine Kinase Inhibitor (IS TKI) in Newly Diagnosed Chronic Myeloid Leukemia in Chronic Phase (CML-CP) in the Pivotal Phase 3 ASC4FIRST Study (ASH 2024) - "Introduction : About 1/3rd of patients (pts) with newly diagnosed CML discontinue/switch treatments (Tx) regardless of TKI (imatinib [IMA], nilotinib [NIL], dasatinib [DAS], or bosutinib [BOS]). ASC's superior efficacy vs all IS TKIs and more favorable safety/tolerability compared with each IS TKI (IMA, NIL, DAS, and BOS) suggests that ASC may transform the CML Tx paradigm. Key secondary endpoints, including MMR rate at wk 96, and other long-term secondary efficacy and safety/tolerability results, will be presented at ASH 2024."

Clinical • P3 data • Atherosclerosis • Cardiovascular • Chronic Myeloid Leukemia • Congestive Heart Failure • Coronary Artery Disease • Gastroenterology • Gastrointestinal Disorder • Heart Failure • Hematological Disorders • Hematological Malignancies • Immunology • Leukemia • Myocardial Infarction • Oncology • Pancreatitis • Respiratory Diseases • Thrombocytopenia

Phenotype-Specific Safety Reporting Signals of Asciminib Versus Second- and Third-Generation Tyrosine Kinase Inhibitors in Chronic Myeloid Leukemia: A FAERS Disproportionality Analysis (SOHO 2026) - "Asciminib was compared with dasatinib, nilotinib, bosutinib, and ponatinib. In FAERS ICSRs restricted to CML and primary suspect drugs, asciminib showed a consistent pattern of disproportionate reporting across multiple prespecified toxicity domains and death outcomes compared with pooled second- and third-generation TKIs. Because ICSRs lack exposure denominators and are subject to underreporting, selective reporting, and confounding by indication, these findings should be interpreted as hypothesis-generating signals that prioritize validation in controlled real-world datasets with exposure adjustment and clinical adjudication and may inform phenotype-directed monitoring while confirmatory analyses are pursued."

Clinical • Chronic Myeloid Leukemia • Hematological Malignancies • Leukemia • Oncology

Cost-Effectiveness Analysis of Asciminib in Patients With Chronic Phase Chronic Myeloid Leukemia Previously Treated With 2 or More Tyrosine Kinase Inhibitors in Colombia. (PubMed, Value Health Reg Issues) - "Asciminib was a dominant treatment option for patients with chronic-phase chronic myeloid leukemia who have been treated with 2 or more tyrosine kinase inhibitors, offering clinical and economic advantages over other pharmacological treatments."

HEOR • Journal • Chronic Myeloid Leukemia • Hematological Malignancies • Leukemia • Oncology

Successful desensitization to bosutinib in chronic myeloid leukemia. (PubMed, Leuk Res Rep) - "After one year, the patient remains asymptomatic, without recurrence of angioedema, and with sustained hematologic control. This is the first published desensitization protocol for bosutinib, enabling continuation of first-line therapy."

Journal • Cardiovascular • Chronic Myeloid Leukemia • Hematological Disorders • Hematological Malignancies • Immunology • Leukemia • Oncology

Macrocyclization of Broad-Spectrum Kinase Inhibitor Bosutinib Leads to Potent and Selective Quinoline-Based HIPK4 Inhibitor AZ137. (PubMed, J Med Chem) - "Its cellular activity was confirmed in cell-based assays of HIPK4-dependent F-actin remodeling. Together with a negative control compound, this probe set provides a foundational framework for validating HIPK4 as a therapeutic target and a high-quality resource to elucidate its roles in normal physiology and disease."

Journal • Non-melanoma Skin Cancer • Oncology • Squamous Cell Carcinoma • Squamous Cell Skin Cancer

Sequential Development of Acute Promyelocytic Leukemia in a Patient With Chronic-Phase CML on Bosutinib: A Rare Dual Myeloid Neoplasm (SOHO 2026) - "Management and Outcome: The patient was treated with all-trans retinoic acid (ATRA) and arsenic trioxide (ATO) with supportive care, including transfusions and monitoring for differentiation syndrome and QT prolongation. This case highlights the importance of prompt bone marrow evaluation in patients with CML who develop unexplained cytopenias. Early recognition of APL enables timely, curative therapy. Clinicians should maintain a broad differential diagnosis and remain vigilant for secondary hematologic malignancies during long-term tyrosine kinase inhibitor therapy."

Clinical • Acute Promyelocytic Leukemia • Chronic Myeloid Leukemia • Hematological Malignancies • Leukemia • Oncology • ABL1 • BCR • RARA

Efficacy and Safety Results from ASC4MORE, a Randomized Study of Asciminib (ASC) Add-on to Imatinib (IMA), Continued IMA, or Switch to Nilotinib (NIL) in Patients (Pts) with Chronic-Phase Chronic Myeloid Leukemia (CML-CP) Not Achieving Deep Molecular Responses (DMRs) with ≥1 Year of IMA (ASH 2022) - P2, P3 | "In the phase 3 ASCEMBL study, ASC led to superior major molecular response vs bosutinib (BOS) at wk 24 and 96...Top reasons for discontinuation were pt decision in the ASC 40-mg add-on arm (9.5%), AEs in the ASC 60-mg add-on and NIL arms (14.3% and 23.8%, respectively), and physician decision in the IMA arm (57.1%) (pts who crossed over to the ASC 60-mg add-on arm were considered discontinued for IMA arm)... More pts achieved DMR at wk 48 with ASC add-on to IMA vs continued IMA or switch to NIL in pts not achieving DMR with IMA alone for ≥1 y. In this population of pts tolerating IMA for ≥1 y, ASC add-on was generally well tolerated. While not powered to identify the best arm for achievement of DMR in this setting, the high rate of DMR in the ASC add-on arms is promising. Further studies are needed to assess if ASC alone can provide equivalent efficacy and better tolerability vs add-on to IMA."

Clinical • Chronic Myeloid Leukemia • Hematological Malignancies • Leukemia • Oncology

Efficacy and safety of asciminib (ASC) in patients (pts) with chronic-phase chronic myeloid leukemia (CML-CP) after 1 tyrosine kinase inhibitor (TKI): Interim analysis (IA) of the phase 2 ASC2ESCALATE trial. (ASCO 2025) - P2 | "Prior treatment (Tx) included dasatinib (44.6%), imatinib (42.6%), nilotinib (9.9%), or bosutinib (5.0%); 66.3% of pts had received prior Tx for ≥12 mo. 2L ASC demonstrated high molecular response rates at wk 24 and safety consistent with previously established ASC data across Tx lines; no new or worsening safety signals arose. ASC was tolerable with few AEs leading to discontinuation. These IA results support ASC as a Tx option in 2L CML-CP."

Clinical • P2 data • Cardiovascular • Chronic Myeloid Leukemia • Hematological Disorders • Hematological Malignancies • Hypertension • Leukemia • Neutropenia • Oncology • Pain • Thrombocytopenia

Assessment of Outcomes After Stopping Tyrosine Kinase Inhibitors Among Patients With Chronic Myeloid Leukemia: A Nonrandomized Clinical Trial. (PubMed, JAMA Oncol) - P=N/A | "Participants were adults with chronic-phase CML whose disease was well controlled with imatinib, dasatinib, nilotinib, or bosutinib. Detectable BCR-ABL1 by RQ-PCR or ddPCR at the time of TKI discontinuation was associated with higher risk of MRec; clinical application of this finding should be confirmed in other studies. ClinicalTrials.gov Identifier: NCT02269267."

Clinical • Journal • Chronic Myeloid Leukemia • CNS Disorders • Depression • Fatigue • Hematological Malignancies • Leukemia • Oncology • Pain • Psychiatry • Sleep Disorder

Reframing chronic myeloid leukemia outcomes beyond survival: a perspective of quality of life and patient-centered data. (PubMed, Blood Rev) - "Commonly used TKIs (imatinib, nilotinib, dasatinib, bosutinib, ponatinib, asciminib, and olverembatinib) all have positive and negative impacts on QoL, each of which can be impacted by patient preference and priorities, as well as line of therapy. The inclusion of patient-reported QoL outcomes in clinical trials will be vital to helping physicians understand the patient experience of CML and thereby improve disease management."

HEOR • Journal • Review • Chronic Myeloid Leukemia • Hematological Malignancies • Leukemia • Oncology

Impact of Mutations in Blood Cancer–Related Genes on Clinical Outcomes in Chronic Myeloid Leukemia in Chronic Phase (CML-CP) after ≥2 Tyrosine Kinase Inhibitors (TKIs) in the Ascembl Trial (ASH 2023) - "With >2 years of follow-up in the phase 3 ASCEMBL study, asciminib (ASC) has continued to demonstrate superior efficacy vs bosutinib (BOS) in pts with CML-CP after ≥2 prior TKIs, and analysis of cancer gene somatic mutations in this population has the potential to reveal additional insights into pts' response to study treatments or characteristics of the disease in later lines of therapy... Adults with CML-CP previously treated with ≥2 TKIs with intolerance of their last TKI or lack of efficacy per 2013 European LeukemiaNet recommendations and without BCR::ABL1 T315I or V299L mutations were randomized 2:1 to ASC 40 mg twice daily or BOS 500 mg once daily... ASXL1 mutations are most frequently detected at CML diagnosis and were enriched at BL in this study of pts with CML-CP previously treated with ≥2 TKIs, which is consistent with a role in TKI resistance. RUNX1 and IKZF1 mutations, which are associated with progression to accelerated or blast phase in CML, were..."

Clinical • Clinical data • Chronic Myeloid Leukemia • Hematological Malignancies • Leukemia • Oncology • ABL1 • ASXL1 • IKZF1 • RUNX1

Improving Outcomes in Chronic Myeloid Leukemia With Early Switch to Second-Generation Generic Tyrosine Kinase Inhibitors: A Study From Resource-Limited Settings in Western India (SOHO 2026) - "At the last follow-up, 62 patients (52.1%) were receiving imatinib, 47 (39.5%) dasatinib, 5 (4.2%) nilotinib, 3 (2.5%) ponatinib, and 2 (1.7%) bosutinib. Our study shows high rates of switching to dasatinib (39.5%) as a second-line therapy, highlighting the potential future benefit of using it as a first-line therapy for all eligible newly diagnosed patients. Avoiding repeated TKI switches is critical, as it is linked to diminished long-term survival. Current findings suggest that the optimal use of second-generation generic TKIs will lead to significant improvements in long-term survival."

Chronic Myeloid Leukemia • Hematological Malignancies • Leukemia • Oncology