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

Comparative Analysis between Imatinib-Based versus Ponatinib-Based Frontline Therapy in Adult Patients with Ph-Positive Acute Lymphoblastic Leukemia (ICBMT 2025) - No abstract available

Clinical • Acute Lymphocytic Leukemia • Hematological Malignancies • Leukemia

Evolving Algorithms Based on New Drug Approvals: What Have We Gained? (SOHO 2025) - "The response rates were much higher than those achieved with interferon and cytarabine — the standard of care at the time...The safety profile of each drug was also different from imatinib as well as among all three — dasatinib, nilotinib, and bosutinib...That was the motivation for the initial attempt to try ponatinib as initial therapy...More recently, the introduction of TKIs specifically targeting the myristoyl pocket — of which asciminib is the first in class — has renewed our hope in making the next leap forward toward our aim for better therapies...For now, the one thing that we know we have gained with new drug approvals is having more options to choose from so we can better serve each patient based on their needs, their characteristics, and their goals. One can only hope we are getting closer to the promise of cure for all patients with CML."

Chronic Myeloid Leukemia • Hematological Malignancies • Leukemia • Oncology

Electrochemical sensors for anticancer drugs used in the targeted therapy of chronic myeloid leukaemia. (PubMed, ADMET DMPK) - "Treatment of chronic myeloid leukaemia includes targeted therapy with tyrosine kinase inhibitors (TKIs): imatinib, dasatinib, nilotinib, bosutinib, ponatinib, and asciminib. The review is intended to serve as a valuable resource for researchers in navigating the latest developments in TKIs' electrochemical sensing platforms. The fast response, high sensitivities and satisfactory recoveries obtained in blood serum and urine samples show the potential for application of the proposed electroanalytical systems in clinical analysis and optimization of chemotherapeutic treatments."

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

Impact of Patient Profiles on Hematologist-Oncologists' Preferences for Treating Newly Diagnosed Philadelphia Chromosome-Positive Acute Lymphoblastic Leukemia (Ph+ ALL) Using Tyrosine Kinase Inhibitors (TKI) in Combination With Chemotherapy: A Discrete Choice Experiment (SOHO 2025) - P3 | "Achieving MRD-negative CR was the primary consideration for physicians, irrespective of patient profiles. Based on the PhALLCON data and elicited preferences, physicians were predicted to select the profile of ponatinib + chemotherapy over imatinib + chemotherapy for all included patient profiles."

Clinical • Combination therapy • Acute Lymphocytic Leukemia • Hematological Malignancies • Leukemia • Oncology

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

Ponatinib Monotherapy Following Combination With Chemotherapy in Patients With Newly Diagnosed Ph+ ALL: Phase 3 PhALLCON Post Hoc Subgroup Analysis (SOHO 2025) - P3 | "Context: The phase 3 PhALLCON study (NCT03589326) met the primary endpoint, showing a higher rate of minimal residual disease (MRD)-negative (BCR::ABL1IS ≤0.01%; MR4) complete remission (CR) at end of induction (EOI) with ponatinib vs imatinib with comparable safety. Single-agent ponatinib maintained durable MRD negativity post C20. With caution due to small patient numbers, these data appear to support the continuous clinical benefit of maintaining MRD negativity and tolerability of ponatinib monotherapy after consolidation and maintenance in combination with chemotherapy in newly diagnosed Ph+ ALL patients."

Clinical • Monotherapy • P3 data • Retrospective data • Oncology

Adult Philadelphia Chromosome-Positive B-ALL in Crohn's Disease: Therapy-Related or Disease-Associated? (SOHO 2025) - "Introduction: Crohn's disease (CD) is frequently managed with biologic agents such as anti-TNF-α therapies (infliximab) and integrin inhibitors (vedolizumab). The patient achieved complete remission with R-hyper-CVAD chemotherapy plus ponatinib, attaining molecular remission (BCR-ABL<0.003) after the first cycle. Despite requiring colostomy for small bowel obstruction during treatment, he successfully completed consolidation therapy and maintains remission (quantitative BCR-ABL levels remained consistently <0.003) after 8 months of POMS maintenance protocol."

Clinical • Acute Lymphocytic Leukemia • Hematological Malignancies • Leukemia • Oncology • ABL1 • BCR • CD20

Efficacy and Safety of Asciminib Compared With Other TKIs in CML: Meta-Analysis of Controlled Studies and Descriptive Review of Single-Arm Cohorts (SOHO 2025) - "In studies included in meta-analysis, patients received asciminib monotherapy or comparator TKIs (eg, imatinib, bosutinib, ponatinib, or investigator's choice). Asciminib offers superior efficacy and lower adverse events compared with other TKIs in controlled studies, while also showing consistent performance across real-world cohorts. These results support the growing role of asciminib in CML management, including in T315I- mutated disease. However, further prospective studies are needed to establish its use as frontline therapy."

Retrospective data • Review • Chronic Myeloid Leukemia • Hematological Malignancies • Leukemia • Oncology • ABL1

First-in-Human Study of Asciminib Monotherapy in Adults With Relapsed/Refractory (R/R) Philadelphia-Positive Acute Lymphoblastic Leukemia (Ph+ ALL) (SOHO 2025) - P1, P1/2 | "Patients were heavily pretreated: 89.3% (n = 25) had two or more prior TKIs, 53.6% (n = 15) had prior ponatinib treatment, and 46.4% (n = 13) had relapse post transplant. Asciminib monotherapy in heavily pretreated patients with Ph+ ALL demonstrated antileukemic activity and was tolerable with favorable safety, consistent with parallel studies of asciminib in CML. Ongoing trials are exploring the combination of asciminib and blinatumomab (NCT06308588) and asciminib with dasatinib, blinatumomab, and steroids (NCT03595917). The current analysis supports exploration of asciminib combination therapy in patients with R/R Ph+ ALL."

Clinical • Monotherapy • P1 data • Acute Lymphocytic Leukemia • Hematological Malignancies • Leukemia • Oncology

Comparison of the Third-Generation Tyrosine Kinase Inhibitor Ponatinib with First- and Second-Generation Tyrosine Kinase Inhibitors for the Treatment of Philadelphia Chromosome-Positive Acute Lymphoblastic Leukemia: A Systematic Review and Bias-Corrected Meta-Analysis (SOHO 2025) - "Objectives: This meta-analysis compares ponatinib with other TKIs (imatinib, dasatinib, nilotinib) in terms of complete molecular response (CMR), overall survival (OS), and event-free survival (EFS). Ponatinib is associated with significantly better survival outcomes compared with other TKIs. However, due to limited safety data, future randomized controlled trials are needed to comprehensively evaluate its safety profile relative to other TKIs."

Retrospective data • Review • Acute Lymphocytic Leukemia • Hematological Malignancies • Leukemia • Oncology • ABL1 • BCR

Treatment Approaches to Chronic Phase of Chronic Myeloid Leukemia (SOHO 2025) - "The front-line approaches consisted of a single-agent therapy with imatinib, nilotinib and ponatinib, or in combination with non-TKIs treatment. Different generations of TKIs remain potentially curable management approaches, which ensure a high CR rate and long-lasting PFS. The Max Foundation provides TKIs to CML patients on a reliable basis and supports health equity in lowand middle-income countries."

Chronic Eosinophilic Leukemia • Chronic Myeloid Leukemia • Hematological Malignancies • Leukemia • Myeloproliferative Neoplasm • Oncology • ABL1 • BCR

Management of High-Risk Philadelphia Chromosome-Positive ALL (SOHO 2025) - "Whether observed differences in prognostic factors reflect different TKI potencies (eg, dasatinib vs ponatinib) remains unknown...This may reflect omission of high-dose cytarabine/methotrexate from these chemotherapy-free regimens...In the ongoing GIMEMA ALL2820 stud — also evaluating blinatumomab and ponatinib — patients with either IKZF1 plus genotype or persistent MRD by PCR for BCR::ABL1 are referred for allogeneic SCT...These variables should all be considered when choosing the appropriate consolidative therapy, including allogeneic SCT, CD19 CAR T cells, and/or intensified CNS prophylaxis. While some uncertainties still remain, it is clear that better therapies and a more complete understanding of the variables that contribute to relapse risk have allowed us to make great strides in the management of Ph + ALL in the past several years, transforming it from one of the most aggressive subtypes of leukemia to one that is now curable in the vast majority of patients."

IO biomarker • Acute Lymphocytic Leukemia • Hematological Malignancies • Leukemia • Oncology • ABL1 • CDKN2A • CDKN2B • IKZF1 • PAX5 • VPREB1

Post Hoc Analysis of MRD Negativity After End of Induction in the Phase 3 PhALLCON Trial (SOHO 2025) - P3 | "Among patients without MRDneg by EOI who continued treatment, a higher proportion receiving ponatinib achieved MRDneg, including deep molecular response, post EOI compared with imatinib. Two-year EFS in these patients appeared longer with ponatinib than with imatinib. These data support clinical benefit and tolerability of continuing ponatinib post EOI to potentially achieve later MRDneg."

Minimal residual disease • P3 data • Retrospective data • Oncology • ABL1

Tyrosine Kinase Inhibitors for Gastrointestinal Stromal Tumor After Imatinib Resistance. (PubMed, Pharmaceutics) - "Sunitinib, regorafenib, and ripretinib are currently approved as standard second-, third-, and fourth-line therapies, each demonstrating efficacy against distinct mutational profiles. Avapritinib, notably effective against PDGFRA D842V mutations, represents a milestone for previously untreatable subgroups. Several alternative agents-such as nilotinib, masitinib, sorafenib, dovitinib, pazopanib, and ponatinib-have shown varying degrees of success in refractory cases or specific genotypes. Investigational compounds, including crenolanib, bezuclastinib, famitinib, motesanib, midostaurin, IDRX-42, and olverembatinib, are under development to address resistant or wild-type GISTs...Future strategies include precision medicine approaches such as ctDNA-guided therapy, rational drug combinations, and novel drug delivery systems to optimize bioavailability and reduce toxicity. Ongoing research will be crucial for refining treatment sequencing and expanding therapeutic options,..."

Journal • Review • Gastrointestinal Cancer • Gastrointestinal Disorder • Gastrointestinal Stromal Tumor • Oncology • Sarcoma • KIT • PDGFRA

Evaluation of the Treatment of Philadelphia Chromosome-Positive Acute Lymphoblastic Leukemia (Ph+ ALL): A Systematic Review (SOHO 2025) - "Studies using imatinib, dasatinib, and ponatinib were evaluated, and showed improved long-term remission and survival rates. This study highlights reduced-intensity chemotherapy and early TKI initiation for Ph+ ALL patients. Despite advancements, AEs and MRD positivity significantly impact survival and reduce allo-HSCT referrals."

Review • Acute Lymphocytic Leukemia • Hematological Malignancies • Leukemia • Oncology • ABL1 • BCR

Treatment Patterns of Asciminib in Philadelphia Chromosome-Positive (Ph+) Acute Lymphoblastic Leukemia (ALL): A Retrospective Cohort Analysis (SOHO 2025) - P1, P1/2 | "Before asciminib, 94.6% received ≥1 TKI, most commonly ponatinib (55.7%) or dasatinib (18.6%) immediately prior. Asciminib was given as combination therapy (73.0%) with chemotherapy (55.4%), inotuzumab ozogamicin (14.9%), blinatumomab (13.5%), or corticosteroids (67.6%), and as monotherapy to 27% of patients... In a real-world setting, asciminib has been used for the treatment of Ph+ ALL, as both monotherapy and combination therapy. The study findings suggest that asciminib is more commonly used at later lines of treatment. Further studies are warranted to explore the unmet needs of patients with Ph+ ALL and the clinical benefits of asciminib."

Retrospective data • Acute Lymphocytic Leukemia • Chronic Myeloid Leukemia • Hematological Malignancies • Leukemia • Oncology • ABL1

Identifying Drug Combination Strategies for ZMYM2: FGFR1 Fusion Positive Leukemia. (PubMed, Precis Oncogenom) - "After initially responding to ponatinib, the patient was switched to pemigatinib which eventually transitioned them to a successful transplant. Leukemia cells isolated from the patient exhibited ex vivo sensitivity to ponatinib, bortezomib and axitinib. ZMYM2:FGFR1-transformed Ba/F3 cells were exquisitely sensitive to next generation FGFR inhibitors, and combinations of FGFRi plus trametinib or midostaurin were found to be synergistic, suggesting novel therapeutic options for FGFR1-fusion positive patients."

Journal • Eosinophilia • Hematological Malignancies • Leukemia • Lymphoma • Oncology • Transplantation • FGFR1 • ZMYM2

Pulmonary and Survival Risks of Third- vs First-Generation BTKIs in Real-World CML: A Multicenter EHR Analysis (SOHO 2025) - "In a large, real-world US cohort, 3G BTKIs conferred substantially higher absolute and relative risks of severe pulmonary events, blast phase progression, and death vs imatinib despite balanced baseline characteristics. Excess harms—such as +5% ARDS and +11% mortality within 12 months—underscore the need for vigilant pulmonary monitoring, risk mitigation, and cautious patient selection when prescribing ponatinib or asciminib."

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

An Evaluation of Adverse Effects in Patients Receiving Tyrosine Kinase Inhibitor Therapy During the Chronic Phase of Chronic Myeloid Leukemia: A Single-Center Experience (SOHO 2025) - " Of the 127 patients included in the study, 49% (n = 62) received imatinib, 25% received dasatinib (n = 32), 16% received nilotinib (n = 20), 7.5% received bosutinib (n = 10), and 2.5% received ponatinib (n = 3). The primary goal of TKI therapy for CML is to maximize antitumor efficacy while minimizing treatment-related toxicities. Awareness of the potential adverse effects is a crucial component of optimal TKI use. Regular monitoring, early recognition, and appropriate intervention, particularly for frequently encountered toxicities, may facilitate long-term treatment success and improve patient outcomes."

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

TKI De-Escalation: The " Downgrading " Impact on CML Treatment (SOHO 2025) - "Prior to downgrading, patients received nilotinib (46%), dasatinib (38%), ponatinib (11%), bosutinib (4%), or asciminib (1%)...Lower - potency agents selected for downgrading included imatinib (67.5%), bosutinib (25.5%), asciminib (3.3%), nilotinib (2.5%), dasatinib (0.6%), and interferon - α (0.6%)...Conclusion By overturning the escalation - only paradigm, this study shows that strategic downgrading of TKIs sustains deep molecular remission, reduces chronic toxicity, unlocks treatment - free remission for a broader swath of CML patients, and — given the availability of multiple lower - potency agents as " generic " drugs — can substantially lower treatment costs, warranting its expansion into further prospective clinical trials. Acknowledgments We thank all the colleagues of CAMPUS CML and our data managing team."

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

Rare Atypical Ela3 BCR-ABL transcript in acute Lymphoblastic Leukemia: a case report. (PubMed, Afr Health Sci) - "She presented with a complex karyotype and showed good early response to imatinib and dasatinib but relapsed six months after diagnosis, and E255v, T315I mutations were successively detected in the ABL kinase region, then he switched to ponatinib and underwent allogeneic hematopoietic stem cell transplantation. But the Minimal Residual Disease increased after 16 months, the patient was treated with CD19 chimeric antigen receptor T cell immunotherapy, and changed to olverembatinib targeted therapy. This subgroup of acute lymphoblastic leukemia might have poorer prognosis than patients with common transcripts. we recommend the third-generation tyrosine-kinase inhibitor as a first choice for their initial therapy and allogeneic hematopoietic stem cell transplantation or immunotherapy and new clinical trials should be considered as early as possible."

IO biomarker • Journal • Acute Lymphocytic Leukemia • B Acute Lymphoblastic Leukemia • Bone Marrow Transplantation • Hematological Malignancies • Leukemia • Oncology • Transplantation • ABL1 • BCR • ELANE

Impact of Adverse Events (AEs) on Health-Related Quality of Life (HRQOL) in Chronic Myeloid Leukemia (CML): Results From the Patient Survey on Humanistic Burden of Intolerance to First or Second Tyrosine Kinase Inhibitors (TKIs) SHIFT Study in the US (SOHO 2025) - "TKIs included imatinib (34%), dasatinib (37%), bosutinib (14%), nilotinib (12%), and ponatinib (3%). TKI-related AEs resulted in humanistic burden. Most patients reported multiple AEs impacting physical/mental health and HRQOL. Employment changes and productivity loss reflected impaired work function."

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

Outcomes of Patients With Chronic Myeloid Leukemia Receiving Second-Line Therapy (SOHO 2025) - "2L consisted of dasatinib in 280 (42%) patients, nilotinib in 160 (24%), bosutinib in 98 (15%), imatinib in 81 (12%), ponatinib in 37 (5%), asciminib in six (1%), and other in three (1%). 2L-induced cytogenetic and molecular remissions is around 40% of CML patients without response to 1L, with a long-term survival of 70%."

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

Cardiovascular Disease in Patients With Chronic Myeloid Leukemia: JACC: CardioOncology State-of-the-Art Review. (PubMed, JACC CardioOncol) - "For instance, dasatinib has been associated with the development of pulmonary arterial hypertension, while nilotinib and ponatinib have been linked to various vascular complications. To accurately evaluate the incidence of CV events associated with CML treatment, systematic documentation of these occurrences in future clinical trials is essential. This approach will facilitate a deeper understanding of the CV implications of tyrosine kinase inhibitor therapy in patients with CML."

Journal • Review • Cardiovascular • Chronic Myeloid Leukemia • Coronary Artery Disease • Hematological Malignancies • Hypertension • Leukemia • Oncology • Peripheral Arterial Disease • Pulmonary Arterial Hypertension • Pulmonary Disease • Respiratory Diseases • ABL1

Novel e4a2 BCR∷ABL1 transcript with insertion of CSE1L exons 9 and 10 in a CML patient: a case report. (PubMed, Front Oncol) - "This unique fusion includes a 298 bp insertion, derived from a CSE1L gene exons 9 and 10, at the fusion site. The patient showed resistance to first-line dasatinib but achieved a molecular response with the third-generation tyrosine kinase inhibitor ponatinib."

Journal • Chronic Myeloid Leukemia • Hematological Malignancies • Leukemia • Oncology • ABL1 • CSE1L