Iclusig (ponatinib) / Takeda, Otsuka, Incyte - LARVOL DELTA

Drug Repurposing by Virtual Screening: Identification of New Already Approved ROCK Inhibitors as Promising Drugs to Target Neurodegeneration. (PubMed, ACS Omega) - "Virtual screening led to the identification of six approved drugs as ROCK inhibitors: ruxolitinib (36), baricitinib (37), ponatinib (38), tivozanib (39), nialamide (40), and tucatinib (41). These findings not only highlight ruxolitinib (36) as a promising candidate for AD but also provide a structural basis for designing novel dual JAK-ROCK inhibitors and pave the way for further in vitro and in vivo studies. Moreover, the validated pharmacophoric map for ROCK inhibition highlights the identification of an affinity pocket that can be useful for the design of new ROCK inhibitors."

Journal • Alzheimer's Disease • CNS Disorders • Inflammation

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

Comprehensive genomic profiling to guide personalized targeted and immunotherapy in gastrointestinal tumors: Subgroup analysis of the ROME trial (ESMO-GI 2025) - P2 | "Funding: Erlotinib, Pertuzumab, Vemurafenib, Trastuzumab Emtansine, Alectinib, Vismodegib, Cobimetinib, Atezolizumab, Trastuzumab, Ipatasertib (GDC-0068), Entrectinib and Pralsetinib were provided by Roche; Everolimus, Lapatinib, Alpelisib were provided by Novartis, Palbociclib and Talazoparib were provided by Pfizer, Ipilimumab and Nivolumab were provided by Bristol Myers Squibb (BMS); Brigatinib was provided by Takeda Pharmaceutical Co.; Ponatinib, Itacitinib (INCB039110), Pemigatinib (INCB054828) were provided by Incyte; Selpercatinib was provided by Eli Lilly; Tepotinib was provided by the healthcare business of Merck KGaA, Darmstadt, Germany (CrossRef Funder ID: 10.13039/100009945). CGP with MTB-guided TT may identify patients with GI cancer who benefit from targeted therapies not routinely available in clinical practice. The roles of TMB and potential disease-specific thresholds deserve further investigation."

IO biomarker • Tumor mutational burden • Colorectal Cancer • Gastrointestinal Cancer • Oncology • Solid Tumor • HER-2 • PIK3CA • TMB

Autophosphorylation of oncoprotein TEL-ABL in myeloid and lymphoid cells confers resistance to the allosteric ABL inhibitor asciminib. (PubMed, Sci Signal) - "In contrast, ATP-competitive tyrosine kinase inhibitors, such as imatinib and ponatinib, were equally effective against both fusion proteins. Nonphosphorylated TEL-ABL was intrinsically susceptible to inhibition by asciminib, but phosphorylation at Tyr89 disassembled the autoinhibited conformation of ABL, thereby preventing asciminib from binding. Our results demonstrate that phosphorylation determines whether an ABL fusion protein is sensitive to allosteric inhibition."

Journal • Hematological Malignancies • Leukemia • Oncology • ABL1 • BCR • ETV6

Ponatinib-induced eruptive squamous cell carcinomas. (PubMed, JAAD Case Rep) - No abstract available

Journal • Oncology • Squamous Cell Carcinoma

Chronic myeloid leukemia in a patient with beta thalassemia major: a rare presentation. (PubMed, Ther Adv Hematol) - "Initial management with imatinib resulted in severe thrombocytopenia and failure to achieve a molecular response. The treatment was then switched to Ponatinib, leading to a favorable outcome with early molecular response. This case report highlights the increased risk of hematological malignancies in thalassemia patients and underscores the importance of vigilant monitoring in them. Furthermore, it emphasizes the role and effectiveness of third-generation tyrosine kinase inhibitors in the management of such cases."

Journal • Beta-Thalassemia • Chronic Myeloid Leukemia • Genetic Disorders • Hematological Disorders • Hematological Malignancies • Leukemia • Oncology • Thrombocytopenia

Targeting WEE1 and asciminib suppresses ABL-tyrosine kinase inhibitor-resistant chronic myeloid leukemia cells. (PubMed, Discov Oncol) - "The combination of asciminib and WEE1 inhibition demonstrated greater efficacy than either drug alone, suggesting a novel therapeutic strategy for treating CML. These findings provide insights into overcoming TKI resistance and highlight a promising approach for future clinical applications."

Journal • Chronic Myeloid Leukemia • Hematological Malignancies • Leukemia • Myeloproliferative Neoplasm • Oncology • ABL1 • PKMYT1 • WEE1

Asciminib for relapsed or refractory Philadelphia chromosome-positive acute lymphoblastic leukemia. (PubMed, Blood Adv) - "Most patients (78%) received ASC as a third-line or later treatment, with 93% previously treated with ponatinib. Post-ASC mutations were analyzed in 7 relapsing patients, identifying a new Q252H mutation in 2 cases. In conclusion, our findings suggest that ASC is an effective salvage therapy for Ph+ ALL and LBC-CML."

Journal • Acute Lymphocytic Leukemia • Chronic Myeloid Leukemia • Hematological Malignancies • Leukemia • Oncology • ABL1

Cardiovascular toxicities associated with vascular endothelial growth factor receptor tyrosine kinase inhibitors: a pharmacovigilance study based on FDA adverse event reporting system. (PubMed, Int J Clin Pharm) - "VEGFR-TKIs were associated with cardiovascular toxicities, particularly hypertension. Notably, lenvatinib and sunitinib were associated with cardiac failure and cardiomyopathy, ponatinib with cardiomyopathy, and vandetanib with Torsade de pointes and QT prolongation. Future prospective studies are warranted to further clarify the causal relationships between these agents and cardiovascular toxicities."

Adverse events • Journal • Cardiomyopathy • Cardiovascular • Congestive Heart Failure • Heart Failure • Hypertension • Oncology

RECURRENT MYOCARDIAL INFARCTIONS IN THE SETTING OF PONATINIB THERAPY: A CARDIO-ONCOLOGY DILEMMA (CHEST 2025) - No abstract available

Cardiovascular • Myocardial Infarction • Oncology

Identification of Olverembatinib as a Potential Inhibitor for ROR1+ Triple-negative Breast Cancer (EACR 2025) - "This study highlights Olverembatinib as a promising ROR1 inhibitor with strong and persistent interactions, making it a viable lead compound for further preclinical validation and development of targeted therapies against ROR1-driven triple-negative breast cancers."

Breast Cancer • Oncology • Solid Tumor • Triple Negative Breast Cancer • ROR1

TARGETING FLT3 IN B-ALL: FROM GENOMIC INSIGHTS TO THERAPEUTIC APPLICATIONS (EHA 2025) - "In vitro studies using 6 FLT3i [Gilteritinib (Gil), Midostaurin, Crenolanib, Sorafenib, Quizartibin and Ponatinib (Pon)] and Venetoclax (Ven) were conducted on pt primary cells and on 11 B-ALL wt and 4 AML cell lines (OCI-AML3 wt; MV-4-11, MOLM-13, MONO-MAC6 FLT3-mut).Data analyses highlight the heterogeneity in FLT3i sensitivity across pediatric ALL cell lines with midostaurin, Pon and quizartinib were among the top scoring drugs for most cell lines (Fig. FLT3 alterations identify a novel subgroup of TN B-ALL with therapeutic potential also in combination regimens."

Acute Lymphocytic Leukemia • Hematological Malignancies • Leukemia • Oncology • Pediatrics • T Acute Lymphoblastic Leukemia • ABL1 • FLT3 • IKZF1 • KMT2A • NUP214 • ZNF384

A NOVEL CONDITIONING REGIMEN WITH ALKYLATING AGENTS, VENETOCLAX, CYTARABINE, CLADRIBINE, AND DECITABINE (ADVANCED) FOR UPFRONT ALLOGENEIC STEM CELL TRANSPLANTATION IN ADVERSE-RISK ACUTE MYELOID LEUKEMIA PATIENTS (EHA 2025) - "Alkylating agents were administered on days -3 and -2 individually (busulfan 3.2 mg/kg (days -3 and/or -2) or thiotepa 5 mg/kg (day -3) + busulfan 3.2 mg/kg (day -2), or melphalan 100 mg/m2 (day -2) based on age, general status, and prior treatment (Figure 1)...GVHD prophylaxis consisted of cyclophosphamide 40 mg/kg (days +3 and +4), a calcineurin inhibitor (from day -1 up to day +60 - +90), and mycophenolate mofetil (from day 0 up to day +35) (Figure 1).We collected patients' and AML characteristics...The ELN 2022 adverse risk aberrations were MECOM rearrangement (1), MECOM rearrangement + TP53 mutation (1), BCR-ABL1 (1), and MDS-related mutations (6).Ponatinib and Gilteritinib were added in two cases with BCR-ABL1 and FLT3 mutations, respectively... The upfront alloSCT with ADVANCED conditioning demonstrates promissing early efficacy for newly diagnosed or R/R adverse-risk AML patients with active disease. The toxicity profile was manageable without unexpected..."

Clinical • Metastases • Acute Myelogenous Leukemia • Febrile Neutropenia • Graft versus Host Disease • Immunology • Infectious Disease • Neutropenia • Transplantation • ABL1 • BCR • FLT3 • MECOM • TP53

FIRST-IN-HUMAN STUDY OF ASCIMINIB (ASC) MONOTHERAPY IN ADULTS WITH RELAPSED/REFRACTORY (R/R) PHILADELPHIA-POSITIVE ACUTE LYMPHOBLASTIC LEUKEMIA (PH+ ALL) (EHA 2025) - P1, P2 | "Pts were heavily pretreated: 89.3% (n=25) had ≥2 prior TKIs, 53.6% (n=15) had prior ponatinib treatment, and 46.4% (n=13) had relapse post transplant. In the current analysis, ASC monotherapy in heavily pretreated pts with Ph+ ALL demonstrated antileukemic activity and was well tolerated, with favorable safety, consistent with parallel studies of ASC in pts with CML. Additional phase 1 cohorts showed that dual treatment with ASC and dasatinib is safe for pts with Ph+ ALL. Ongoing trials are exploring the combination of ASC and blinatumomab (NCT06308588) and ASC with dasatinib, blinatumomab, and steroids (NCT03595917)."

Clinical • Monotherapy • P1 data • Acute Lymphocytic Leukemia • Anemia • Chronic Myeloid Leukemia • Hematological Disorders • Hematological Malignancies • Infectious Disease • Leukemia • Neutropenia • Oncology • Pneumonia • Respiratory Diseases • Thrombocytopenia

HEALTH-RELATED QUALITY OF LIFE BENEFITS OF FRONTLINE PONATINIB PLUS BLINATUMOMAB IN ADULT PATIENTS WITH PH+ ACUTE LYMPHOBLASTIC LEUKEMIA. PRELIMINARY ANALYSIS OF THE GIMEMA ALL2820 TRIAL (EHA 2025) - "We report the first evidence-based data on HRQoL of adult patients with newly diagnosed Ph+ ALL treated in induction/consolidation with ponatinib plus blinatumomab. Our findings indicate notable HRQoL improvements across all age groups, although younger patients seem to benefit the most from this novel treatment approach, devoid of systemic chemotherapy. Further analyses will elucidate on the value of this approach compared with standard of care."

Clinical • HEOR • Acute Lymphocytic Leukemia • Fatigue • Hematological Malignancies • Leukemia • Oncology • Pain • Pulmonary Disease

VENETOCLAX IN COMBINATION WITH CYTARABINE AND ACTINOMYCIN D (ACTIVE) FOR RELAPSED OR REFRACTORY ACUTE MYELOID LEUKEMIA (EHA 2025) - "Venetoclax exposure was confirmed in 13% (14/107) of cases, and 25 % (26/107) had relapsed after a previous alloSCT.Gilteritinib, trametinib, ivosidenib, ponatinib, and dasatinib were added to ACTIVE in 22 % (23/107), 4 % (4/107), 2 % (2/107), 1 % (1/107), and 1 % (1/107), respectively.The ORR was 78 % (82/105), and the CRc rate was 62 % (65/105) with 45 % (29/65) achieving MRD negativity. ACTIVE-based salvage treatment demonstrates promissing antileukemic efficacy with a high bridge-to-alloSCT rate in R/R AML."

Combination therapy • Acute Myelogenous Leukemia • Hematological Disorders • Hematological Malignancies • Infectious Disease • Leukemia • Oncology

Outcome of second allogeneic hematopoietic cell transplantation in adult patients with relapsed B-cell acute lymphoblastic leukemia in the era of new immunotherapeutic agents. (PubMed, Bone Marrow Transplant) - "With the introduction of newer immunotherapeutic agents including blinatumomab, inotuzumab ozogamicin, and ponatinib, we got more chances for allo-HCT2 expecting more promising transplantation outcomes. Our findings highlighted the efficacy of newer salvage therapies in Ph-negative B-ALL, while underscores the need for alternative strategies for Ph-positive ALL. Overall, relapses after allo-HCT2 are still challenging which emphasize the need for strategies other than allo-HCT3 including newer agents such as chimeric antigen receptor (CAR)-T/NK therapies or post-transplant minimal residual disease targeted therapies."

Journal • Acute Lymphocytic Leukemia • B Acute Lymphoblastic Leukemia • Hematological Malignancies • Leukemia • Oncology • Transplantation

Treatment of Philadelphia positive acute lymphoblastic leukemia. (PubMed, Acta Haematol) - "The introduction of tyrosine kinase inhibitors (TKIs), such as imatinib, dasatinib, and ponatinib, has revolutionized frontline therapy, significantly improving remission rates and long-term survival. More recently, immunotherapeutic strategies-including the bispecific T-cell engager blinatumomab and chimeric antigen receptor (CAR) T-cell therapies-have emerged as effective alternatives to conventional chemotherapy and TKIs. This review outlines the major advances in the management of Ph+ ALL, emphasizing the move toward more personalized, targeted, and less toxic treatment approaches."

Journal • Review • Acute Lymphocytic Leukemia • Bone Marrow Transplantation • Hematological Malignancies • Leukemia • Oncology • Transplantation

INDIVIDUALIZED AND INCLUSIVE STRATEGIES FOR TREATING JEHOVAH'S WITNESSES WITH ACUTE LEUKEMIA AND HIGH-GRADE MYELOID NEOPLASMS (EHA 2025) - "Treatments included: 7+3, attenuated decitabine+venetoclax, and azacitidine and sorafenib...One, treated with dasatinib+HyperCVAD, relapsed after 9 mos, then received Ponatinib+Blinatumomab, and underwent stem cell transplant...The third pt was treated with cyclophosphamide/topotecan for a co-occurring neuroblastoma without response, switching to blinatumomab then hospice due to neuroblastoma progression.For MDS - 1 pt received luspatercept for 8 mos before cessation due to cytopenia (Hgb of 2.9 g/dL)...TPO agonists included romiplostim at 2 to 4 mcg/kg weekly or daily eltrombopag, while G-CSF (Filgrastim, 5 mcg/kg) was administered based on ANC levels. Our study of Jehovah's Witness pts with acute leukemia and high-grade MDS underscores the possibility of individualized leukemia-directed care despite transfusion limitations. Despite significant baseline cytopenias, individualized treatment approaches and the use of hematopoietic growth factors can facilitate the..."

Clinical • Acute Lymphocytic Leukemia • Acute Myelogenous Leukemia • Chronic Myeloid Leukemia • Chronic Myelomonocytic Leukemia • Hematological Disorders • Hematological Malignancies • Infectious Disease • Leukemia • Myelodysplastic Syndrome • Myelofibrosis • Neuroblastoma • Oncology • Septic Shock • Solid Tumor • NPM1

SEQUENTIAL ALLOGENEIC STEM CELL TRANSPLANTATION FOR VENETOCLAX-EXPOSED RELAPSED OR REFRACTORY ACUTE MYELOID LEUKEMIA OR MYELODYSPLASTIC SYNDROME WITH INCREASED BLASTS-2 (EHA 2025) - "Three different 10-day preconditioning backbone regimens were used: ACTIVE (actinomycin D 12.5 mcg/kg (days 1-3), cytarabine 20 mg/m2 (days 1-10), venetoclax 600 mg (days 1-10), De-ACTIVE (decitabine 20 mg/m2 (days 1-10) added to ACTIVE) or De-CAVE (decitabine 20 mg/m2 (days 1-10), cytarabine 20 mg/m2 (days 1-10), venetoclax 600 mg (days 1-10)...Gilteritinib, revumenib, and BCR-ABL1 inhibitor exposure was reported in 16 % (4/25), 12 % (3/25), and 8 % (2/25), respectively...Cladribine (40 %, 10/25), gilteritinib (12 %, 3/25), trametinib (16 %, 4/25), navitoclax (28 %, 7/25), and ponatinib (8 %, 2/25) were added to the preconditioning... Upfront sequential alloSCT demonstrates high antileukemic efficacy in poor-risk, R/R AML, or MDS-IB2 patients with previous venetoclax exposure."

Acute Myelogenous Leukemia • Infectious Disease • Mucositis • Myelodysplastic Syndrome • Septic Shock • Transplantation • BCR • TP53

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

Distinct endothelial cell toxicities mediate thrombotic risk of BCR-ABL tyrosine kinase inhibitors (ISTH 2025) - "However, when the HCAECs were treated with dasatinib or ponatinib, platelet adhesion increased over 5 fold while imatinib, nilotinib, and asciminib had no effect. BCR-ABL-TKIs had no impact on EC expression of thrombomodulin while nilotinib alone increased vWF levels. Table or Figure Upload"

Chronic Myeloid Leukemia • Hematological Malignancies • Leukemia • Oncology • Thrombosis • ABL1 • BCR • THBD

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

THE STUDY ON THE EFFECTS AND MECHANISMS OF TYROSINE KINASE INHIBITORS ON THE FUNCTION OF CD19 CAR-T CELLS (EHA 2025) - "CAR-T cells and B-ALL cells co-cultured killing cytotoxicity experiments found that high concentrations of Imatinib(IM), Nilotinib(NL), Dasatinib(DS), and Ponatinib(PN) reduced the ability of CAR-T cells to target and kill tumors, the level of degranulation, and the secretion of CKs during the killing process. TKIs in the higher concentration range could inhibit the proliferation of CAR-T cells significantly, but they have a limited effect on promoting apoptosis. DS and PN reduced the proportion of CD8+ cells and TTE cells in CAR-T cells. It can slightly inhibit the anti-tumor ability of CAR-T cells and reduce the CK release level at the same time, but DS and PN in mice retained their tumor-cytotoxic effect while reducing the secretion of CK."

CAR T-Cell Therapy • IO biomarker • B Acute Lymphoblastic Leukemia • Hematological Malignancies • Leukemia • Oncology • CD8 • TNFRSF10B

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