bosutinib / Generic mfg. - LARVOL DELTA

Autophagy suppression via SRC induction represents a therapeutic vulnerability for BAP1-mutant cancers. (PubMed, Autophagy) - "Treatment of these cells with SRC inhibitors (such as dasatinib, bosutinib and saracatinib) and autophagy-inducing drugs (such as Tat-BECN1, SW076956 and SW063058) demonstrated a synergistic interaction between these compounds both in vitro and in ovo using a chick Chorioallantoic Membrane (CAM) assay. Our findings elucidate a novel BAP1-SRC-BECN1-autophagy regulatory axis that can be exploited therapeutically in precision oncology through the combination of SRC inhibitors and autophagy inducers, contingent upon patient stratification for BAP1 loss.Significance: Deadly cancers with BAP1 mutations suppress autophagy by phosphorylating the autophagy regulator BECN1 via the proto-oncogene SRC. Treatment with SRC inhibitors and autophagy inducers exhibited synergism in vitro, in ovo and in patient-derived tumor organoids with BAP1 loss, paving the way for treating BAP1-deficient cancers with autophagy inducers and kinase inhibitors."

Journal • Biliary Cancer • Cholangiocarcinoma • Clear Cell Renal Cell Carcinoma • Eye Cancer • Genito-urinary Cancer • Melanoma • Oncology • Solid Tumor • Uveal Melanoma • BAP1 • BECN1

ASC4FIRST: A Study of Oral Asciminib Versus Other TKIs in Adult Patients With Newly Diagnosed Ph+ CML-CP (clinicaltrials.gov) - P3 | N=405 | Active, not recruiting | Sponsor: Novartis Pharmaceuticals | Trial completion date: Jan 2028 ➔ Jan 2031

Trial completion date • Chronic Myeloid Leukemia • Hematological Malignancies • Leukemia • Oncology • ABL1 • BCR

ASC4REAL-2: A Real-world Chronic Myelogenous Leukemia (CML) Patient Disease Registry to Describe Patient Experience and Clinical Outcomes Among Patients With CML Receiving Approved First or Second Line Tyrosine Kinase Inhibitor (TKI) Therapy (clinicaltrials.gov) - P=N/A | N=1000 | Not yet recruiting | Sponsor: Novartis Pharmaceuticals

New trial • Real-world evidence • Chronic Myeloid Leukemia • Hematological Malignancies • Leukemia • Oncology

Cardiovascular toxicity from tyrosine kinase inhibitors in chronic myeloid leukemia with severe dilated cardiomyopathy. (PubMed, Int J Hematol) - "Following a diagnosis of CML, the patient experienced various CVEs with TKIs, including dasatinib, bosutinib, imatinib, and nilotinib. This treatment was well tolerated without any CVEs. Given its minimal off-target activity and lower reported incidence of CVEs, asciminib may offer a viable and safer therapeutic option for CML patients with advanced cardiovascular comorbidities, including those awaiting heart transplantation."

Journal • Cardiomyopathy • Cardiovascular • Chronic Myeloid Leukemia • Hematological Malignancies • Leukemia • Oncology • Transplantation • ABL1

Management of chronic myeloid leukemia in 2025. (PubMed, Cancer) - "Today, the six approved BCR::ABL1 TKIs, five in frontline therapy (imatinib, dasatinib, bosutinib, nilotinib, and asciminib) and all six in later line therapy (including ponatinib), fulfill in one form or another these requirements. Third-generation TKIs that target the ABL1 kinase domain (olverembatinib and ELVN-001) or the myristoyl pocket (TGRX-678 and TERN-701) are under development...However, serious complications, such as graft-vs-host disease, or death could occur. This review summarizes relevant information concerning the management of CML in 2025, and addresses some CML treatment pathways that became entrenched in the management of CML in the first 15-20 years of TKI experience, which may need to be revisited."

Journal • Review • Bone Marrow Transplantation • Chronic Myeloid Leukemia • Graft versus Host Disease • Hematological Malignancies • Immunology • Leukemia • Oncology • Transplantation • ABL1

Development of Takayasu Arteritis During Deep Molecular Response of Chronic Myeloid Leukemia: A Case Report and Literature Review. (PubMed, Mod Rheumatol Case Rep) - "A 28-year-old female was diagnosed with CML in December 2020 and achieved deep molecular response with bosutinib treatment...This case highlights the importance of monitoring for vasculitic complications in CML patients, even during molecular response. The temporal relationship between these conditions suggests that inflammatory mechanisms leading to vasculitis might persist or develop independently of CML disease activity, challenging the conventional understanding of their association as purely paraneoplastic phenomenon."

Journal • Chronic Myeloid Leukemia • Fatigue • Hematological Malignancies • Leukemia • Oncology • Pain • Vasculitis

A Rare Case of Small Lymphocytic Lymphoma (SLL) Arising After Chronic Myeloid Leukemia (CML) in a Single Patient. (PubMed, Cureus) - "His CML was initially managed with bosutinib, later switched to dasatinib due to side effects, resulting in both cytogenic and molecular response. Two years later, he was diagnosed with SLL. This report explores the potential molecular mechanisms underlying the coexistence of these distinct hematologic malignancies and highlights important considerations in the selection of appropriate treatment strategies."

Journal • Chronic Lymphocytic Leukemia • Chronic Myeloid Leukemia • Hematological Disorders • Hematological Malignancies • Leukemia • Lymphoma • Non-Hodgkin’s Lymphoma • Oncology • Small Lymphocytic Lymphoma

Transcriptional profiling and ex vivo drug pre-screen for personalized therapy selection (EACR 2025) - "PDXO drug treatment experiments determined the efficiency of PDAC standard-of-care combinations gemcitabine & nab-paclitaxel and folfirinox. Additionally, predicted compounds showed reduced organoid viability, such as AT9283, plicamycin, belinostat, lapatinib, trametinib, olaparib, or bosutinib... Drug resistance remains a major challenge in PDAC treatment, demonstrating the need for new therapies. Our findings highlight organoids as a robust model for testing tumor epithelial cell-targeting compounds, offering a key advantage in personalized drug screening due to in vitro expansion potential. Using a newly developed PDX model and derived PDXOs, we demonstrated the feasibility of testing SOC drugs and therapies predicted from transcriptomic data."

Preclinical • Oncology • Pancreatic Cancer • Pancreatic Ductal Adenocarcinoma

Bosutinib Restores the Sensitivity of Colistin against Mcr-1-Positive E. coli. (PubMed, ACS Infect Dis) - "In conclusion, the present study reveals that bosutinib restores the antimicrobial activity of colistin through dual mechanisms: membrane permeability enhancement and direct targeting of the MCR-1 protein. Indeed, the discovery of bosutinib not only expands the application of tyrosine kinase inhibitor analogues in the field of anti-infective drugs but also provides a potentially new alternative for the clinical treatment of MCR-1-positive bacterial infections."

Journal • Infectious Disease

CHRONIC MYELOID LEUKEMIA MONITORING EXPERIENCE IN ECUADOR, SOLCA - GUAYAQUIL (2015-2024) (EHA 2025) - "The number of tests performed to each case ranged from a single one up to 22 during this period.Of 377, 207 (55%) used a first generation TKI (IMATINIB) of which 163/207(78.7%) had no response (NR), 33/207(16%) reached MR3 and 11/207 (5.3%) MR4.5; 158/377(41.9%) used a second generation TKI (2G) (NILOTINIB/DASATINIB/BOSUTINIB) showing NR in 78/158 cases (49.4%), 60/158 (38%) MR3 and 20/158(12.6%) MR4.5. During 9 years we have performed 2238 qPCR detecting BCR::ABL chimeric transcript to 414 patients diagnosed as CML. Most of the cases presented the fusion transcript b2a2/b3a2. The patients treated with IMATINIB had a high NR (78.7%) than TKI-2G (42%)."

Chronic Myeloid Leukemia • Hematological Malignancies • Leukemia • Oncology • Pediatrics • ABL1

IMPACT OF ADVERSE EVENTS ON QUALITY OF LIFE IN CHRONIC MYELOID LEUKEMIA (CML) – RESULTS FROM THE PATIENT SURVEY ON HUMANISTIC BURDEN OF INTOLERANCE TO FIRST OR SECOND TKIS (SHIFT) STUDY IN THE US (EHA 2025) - "TKIs utilized included imatinib (34%), dasatinib (37%), bosutinib (14%), nilotinib (12%), or ponatinib (3%).Patients reported a median of 3 AEs (range: 0-14) in the last 7 days. Findings from the SHIFT study demonstrate the substantial humanistic burden of TKI-related AEs among patients with CML in the US. Most patients had multiple persistent AEs, negatively impacting physical and mental health, contributing to worse QoL. In addition, the extent of work productivity impairment is reflected in the high proportion modifying employment due to CML and, among those employed, experiencing some work productivity loss."

Adverse events • Clinical • HEOR • Chronic Myeloid Leukemia • Fatigue • Hematological Malignancies • Leukemia • Mood Disorders • Musculoskeletal Diseases • Musculoskeletal Pain • Oncology • Orthopedics • Pain • Psychiatry

LOW SERUM IL-8 MAY CONTRIBUTES TO TREATMENT-FREE REMISSION IN CHRONIC MYELOID LEUKEMIA (EHA 2025) - "We reported that changes in effector regulatory T cells (eTreg) early after discontinuation were associated with a better prognosis in a Japanese imatinib discontinuation study (Cancers 2021). This indicates that imatinib-sensitive eTreg may serve as a biomarker reflecting host immune responses during the TFR phase. Subsequently, a similar phenomenon was observed with dasatinib and bosutinib, but no change in eTreg was observed only after discontinuation of nilotinib."

Clinical • Chronic Myeloid Leukemia • Hematological Malignancies • Leukemia • Oncology • CXCL8 • IFNG • IL1B • IL6 • TNFA

SECOND TREATMENT FREE REMISSION AFTER COMBINATION THERAPY WITH RUXOLITINIB PLUS TYROSINE KINASE INHIBITORS IN CHRONIC PHASE CHRONIC MYELOID LEUKEMIA (CML) (EHA 2025) - P2 | "Eligible pts met the following criteria: 1) confirmed diagnosis of CP-CML; 2) previously discontinued TKI therapy per NCCN guidelines; 3) had molecular recurrence; 4) restarted the same TKI they received prior to first TFR attempt.This trial combined rux 15mg BID plus BCR-ABL TKI (imatinib, dasatinib, nilotinib or bosutinib) for 12 28-day cycles in the combination treatment phase (CTP). This single-arm, phase 2 trial found that adding rux after re-initiation of TKI does not improve the rates of second-TFR. This may be partially confounded by a higher-than-expected drop-out rate during CTP. Additional work to characterize the distribution and expression of T/NK cells is ongoing to differentiate pts who achieved successful TFR vs those who did not."

Clinical • Combination therapy • Anemia • Chronic Myeloid Leukemia • Fatigue • Hematological Disorders • Hematological Malignancies • Leukemia • Leukopenia • Neutropenia • Oncology • ABL1 • BCR

ASSESSMENT OF TRANSITIONING FROM HIGH-POTENCY TO LOW-POTENCY INHIBITORS IN CHRONIC MYELOID LEUKEMIA (CML) PATIENTS: THE DOWNGRADING-IMPACT (D-IMPACT) PROJECT, A CML CAMPUS STUDY (EHA 2025) - "TKIs before downgrading: Nilotinib (NIL) (n=73; 46%), Dasatinib (DAS) (n=60; 38%), Ponatinib (n=17; 11%), Bosutinib (BOS) (n=6; 4%), Asciminib (n=1; 1%)...The TKIs used for downgrading were imatinib (IMA) 106 (67.5%), Bosutinib 40 (25.5%), Nilotinib 4 (2.5%), Dasatinib 1(0.6%), Asciminib 5 (3.3%), Interferon 1 (0.6%) (Fig1A)... This exploratory study shows that a downgrading approach can be strategic and safely considered in CML patients, especially for long-term treatment maintaining therapeutic efficacy without adverse clinical outcomes."

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

ASCIMINIB AFTER ONE PRIOR TYROSINE KINASE INHIBITOR IN PATIENTS WITH CHRONIC MYELOID LEUKEMIA – A PHYSICIAN PANEL-BASED CHART REVIEW STUDY IN THE UNITED STATES (EHA 2025) - "Imatinib (49.8%), dasatinib (34.5%), nilotinib (10.6%), and bosutinib (5.1%) were received as first TKI. In this first real-world study among patients with CML-CP treated with asciminib after one prior TKI, most patients remained on treatment and achieved or maintained MMR, suggesting that asciminib was well tolerated and effective, consistent with earlier line trials. Findings were consistent across subgroups, indicating that asciminib is an effective option for all patients, including those intolerant or resistant to their first TKI."

Clinical • Review • Chronic Myeloid Leukemia • Fatigue • Hematological Disorders • Hematological Malignancies • Leukemia • Oncology • Pain • ABL1

CHALLENGES IN TREATING CML PATIENTS IN LOW INCOME COUNTRIES: A SINGLE CENTRE EXPERIENCE (EHA 2025) - "Therapy modification was required in 21% of cases, with 12.6% switching from imatinib to dasatinib due to suboptimal response and 8.4% due to drug intolerance. Additionally, 2.5% of dasatinib-treated patients were switched to nilotinib, 1.7% to bosutinib, and 1.7% to ponatinib... Despite the availability of generic first-generation TKIs, 7.75% of patients did not initiate therapy, indicating barriers to treatment access and adherence. The observed suboptimal response rates were higher than reported in the literature, likely due to poor drug adherence and irregular supply of TKIs in government healthcare settings. Addressing these challenges is essential to improving treatment outcomes and bridging the disparity in CML management in developing nations."

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

INTERIM ANALYSIS (IA) RESULTS FROM ASC2ESCALATE SUPPORT ASCIMINIB (ASC) AS A TREATMENT (TX) OPTION IN CHRONIC-PHASE CHRONIC MYELOID LEUKEMIA (CML-CP) AFTER 1 TYROSINE KINASE INHIBITOR (TKI) (EHA 2025) - P2 | "Pts had received prior dasatinib (44.6%), imatinib (42.6%), nilotinib (9.9%), or bosutinib (5.0%) for ≥12 mo (66.3%), ≥6 to <12 mo (15.8%), or <6 mo (17.8%). In the first prospective trial of 2L ASC in CML-CP, ASC provided high wk 24 molecular response rates and safety and tolerability consistent with previously established 1L and 3L+ ASC data. No new or worsening safety signals arose, and AEs led to discontinuation in <5% of pts. These IA results support ASC as a 2L tx option in CML-CP."

Cardiovascular • Chronic Myeloid Leukemia • Dyspepsia • Hematological Disorders • Hematological Malignancies • Hypertension • Leukemia • Movement Disorders • Neutropenia • Oncology • Pain • Thrombocytopenia

DISCONTINUING TKIS IN CML PATIENTS LACKING DEEP MOLECULAR RESPONSE: RISK OR OPPORTUNITY? AN EXPLORATORY STUDY FROM THE ITALY-TFR REGISTRY (EHA 2025) - P=N/A | "Twenty-three pts (59%) had to resume therapy (Fig.1), median time to restart treatment for these pts was 7.36 mos (IQR: 3.49 - 10.5).Pts who had to restart therapy were 9 treated with imatinib, 3 with nilotinib, 7 with dasatinib, 3 with bosutinib, 1 with ponatinib (12 pts stopped TKI in frontline, 11 pts in 2nd or further lines). Our population is heterogeneous and worthy of more detailed analysis to better understand which characteristics make the outcome so favorable in this unexpected population. Duration of TKI treatment before stopping could be a potential predictor of successful TFR also in pts lacking DMR."

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

DE-ESCALATION AND TREATMENT-FREE REMISSION IN CHRONIC MYELOID LEUKEMIA PATIENTS RECEIVING SALVAGE THERAPY FOR RESISTANCE, WARNING OR LACK OF DEEP MOLECULAR RESPONSE (EHA 2025) - "Imatinib was the 1st line TKI in all but one pt who received nilotinib...Last TKI prior to discontinuation was a 2nd generation drug (dasatinib, nilotinib or bosutinib) in 88% of pts, a 3rd generation compound (ponatinib) in 7% of pts and the allosteric TKI asciminib in 2% of pts... TKI discontinuation is pts with prior history of resistance, warning or lack of DMR appears feasible and safe in our experience. A larger series is required to draw firm conclusions, but our results pave the way for recommendations in clinical practice. Maintenance of a DMR after therapy de-escalation might identify pts with high probabilities of TFR success."

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

ACHIEVING TREATMENT FREE REMISSION IN CML PATIENTS TREATED WITH BOSUTINIB: DATA FROM THE ITALY-TFR REGISTRY (EHA 2025) - P=N/A, P3 | "While TKI discontinuation has become clinical practice for patients (pts) treated frontline with imatinib, nilotinib and dasatinib who achieve a stable deep molecular response (DMR), data on bosutinib discontinuation are more limited and further studies are needed to assess its potential for treatment free remission (TFR). In fact only a single center study focusing on ponatinib and bosutinib discontinuation is reported, which includes 8 pts who discontinued bosutinib mostly due to toxicity...One patient restarted bosutinib, 1 patient started asciminib, 1 patient nilotinib and 1 patient imatinib... Our preliminary analysis suggests that discontinuing Bosutinib is as safe as discontinuing other TKIs, confirming the single center experience reported in literature. Our patients suspended by clinical decision rather than toxicity. The depth of molecular response was the strongest predictor of successful TFR for the cases already reported in literature."

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

COMPARATIVE EFFECTS OF THE ALLOSTERIC INHIBITOR ASCIMINIB AND ATP-COMPETITIVE TYROSINE KINASE INHIBITORS ON BONE METABOLISM (EHA 2025) - "To assess the impact of TKIs on bone metabolism, we examined the effects of imatinib, dasatinib, bosutinib, and asciminib on osteoclast and osteoblast function. Our results suggest that the allosteric ABL1 kinase inhibitor asciminib may have a milder impact on bone metabolism than the conventional ATP-competitive TKIs. This reduced effect on bone remodeling could be beneficial for pediatric CML patients by mitigating growth impairment associated with long-term TKI therapy."

Chronic Myeloid Leukemia • Hematological Malignancies • Leukemia • Oncology • Pediatrics

PILOT STUDY WITH SINGLE CELL TRANSCRIPTOMICS ANALYSIS OF RESIDUAL DISEASE IN PATIENTS WITH CHRONIC MYELOID LEUKEMIA. (EHA 2025) - "In this study, more than 2 million viable cells have been obtained from each patient using the Cell Drop FLi fluorescence counter, which were subsequently subjected to transcriptomic analysis.The study included 2 males and 2 females, aged between 53-63 years, each with a different response profile to TKIs.A 62-year-old female, 29 years after CML Ph diagnosis, ´never achieved a molecular response despite undergoing various therapies (Hydroxyurea, alpha -Interferon, AraC-Interferon, Imatinib, Dasatinib, Nilotinib, Bosutinib). This study provides a new approach to understanding the molecular response in CML and offers preliminary insights into the role of key genes in the disease."

Clinical • Residual disease • Chronic Myeloid Leukemia • Hematological Malignancies • Leukemia • Oncology • Orthopedics • ABL1 • BCR

APPLICABILITY OF THE HFA-ICOS SCORE AS A CARDIOVASCULAR RISK ASSESSMENT TOOL IN CML PATIENTS (EHA 2025) - "The most prevalent risk factor was hypertension (HTN) at 45.6%, followed by diabetes and dyslipidemia, both at 29.3%.The most frequent first-line TKI was imatinib (60.5%), followed by nilotinib (27.5%), dasatinib (10.9%), and bosutinib (1.1%). At the time of the vascular event, 58.8% of patients were on nilotinib, 23.5% on imatinib, and 11.8% on ponatinib.According to the HFA-ICOS score calculated at diagnosis, 13.3% of patients were classified as very high risk (VHR), 33.3% as high risk (HR), 23.3% as moderate risk (MR), and 30% as low risk (LR).During follow-up, 18 vascular events were recorded in 17 patients (19.6%)... The predictive value of the HFA-ICOS score for cardiovascular toxicity to TKI treatment was confirmed in our CML cohort, in accordance with the few studies published to date.The HFA-ICOS score may be an effective tool for the cardiovascular risk stratification of CML patients at diagnosis, facilitating decision-making in the individualized selection of..."

Clinical • Cardiovascular • Chronic Myeloid Leukemia • Diabetes • Dyslipidemia • Hematological Malignancies • Hypertension • Leukemia • Metabolic Disorders • Oncology • ICOS

Biohybrid motor neuron spheroid composed of graphene/HUVEC/neural cell for 3D biosensing system to evaluate drug of amyotrophic lateral sclerosis. (PubMed, Nano Converg) - "Reduced contraction of the connected muscle bundle due to ALS could be restored by upon treatment with the bosutinib, ALS drug, demonstrating the potential use for drug screening. The method to generate biohybrid spheroid can be applied to generation of various biohybrid brain organoids, and the proposed 3D NMJ biosensing system can be used to drug screening of diverse neuromuscular diseases."

Journal • Amyotrophic Lateral Sclerosis • CNS Disorders

SEX AFFECTS BOSUTINIB DOSING, TOLERABILITY, AND EFFICACY IN PATIENTS WITH CHRONIC MYELOID LEUKEMIA: POST HOC ANALYSIS OF THE BODO STUDY. (EHA 2025) - P2 | "Despite the equal target bosutinib DD of 500 mg, female patients of the BODO study received significantly lower bosutinib DD than male patients and discontinued bosutinib treatment more often. Additionally, TEAEs occurred earlier in female patients. However, MMR and MR4 rates attributed to bosutinib did not differ between both sexes and MR4.5 rate was higher in female patients compared to male patients."

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