Iclusig (ponatinib) / Takeda, Otsuka, Incyte, Endo, Specialised Therap, Pint Pharma, Biologix Pharma - LARVOL DELTA

ENABLE: A Phase 1 Study of ELVN-001, a Novel, Selective ATP-Competitive Inhibitor of BCR::ABL1, in Patients With Previously Treated CP-CML (SOHO 2026) - P1 | " Of 141 patients (median age, 58 years), nine had atypical BCR::ABL1 transcripts and 28 had ABL1 kinase mutations (15 with T315I; 12 with asciminib-resistance mutations); 67% received ≥3 prior TKIs (24% with ≥5 TKIs; 61% prior asciminib; 38% prior ponatinib), with 64% discontinuing the prior TKI due to lack of efficacy (according to ELN guidelines). In this updated analysis of ENABLE, ELVN-001 showed favorable safety and tolerability and robust anti-CML activity in heavily pretreated patients. ABL1: ABL proto-oncogene 1, non-receptor tyrosine kinase, ATP: adenosine triphosphate, BCR::ABL1: breakpoint cluster region–Abelson 1, CML: chronic myeloid leukemia, CP: chronic phase, ELN: European LeukemiaNet, MMR: major molecular response, T315I: threonine-to-isoleucine mutation at position 315."

Clinical • P1 data • Chronic Myeloid Leukemia • Oncology • ABL1 • BCR

18-Months Follow-up of the Trial of Imatinib after Ponatinib Induction (TIPI) in the Front-Line Treatment of Chronic Phase (CP) Chronic Myeloid Leukemia (CML) Setting (ASH 2024) - P2 | "Ponatinib induction followed by imatinib consolidation induces high rates of MMR and DMR at M18, higher than that with TKI2 as front-line therapy as reported in the literature in CP-CML pts. Whether or not this translates into substantial TFR rates is yet to be determined."

Breast Cancer • Cardiovascular • Chronic Myeloid Leukemia • CNS Disorders • Diabetes • Epilepsy • Gastroenterology • Gastrointestinal Disorder • Hypertension • Infectious Disease • Metabolic Disorders • Neutropenia • Osteoarthritis • Solid Tumor • Thrombosis • ABL1

Genetic correlates in patients with Philadelphia chromosome-positive acute lymphoblastic leukemia treated with Hyper-CVAD plus dasatinib or ponatinib. (PubMed, Leukemia) - "Among them, IKZF1 deletion was associated with poor prognosis in patients treated with imatinib-based or dasatinib-based regimens. In a multivariate analysis, dasatinib therapy, lack of achievement of 3-month complete molecular response, and the presence of IKZF1 status were significantly associated with poor OS. The differential impact of IKZF1 was largely restricted to patients given Hyper-CVAD plus ponatinib; dasatinib-based regimens had unfavorable outcomes regardless of the molecular abnormalities."

Journal • Acute Lymphocytic Leukemia • Hematological Malignancies • Leukemia • Oncology • IKZF1

Frontline Blinatumomab and Ponatinib in Ph+ Acute Lymphoblastic Leukemia: A Single-Center Real-World Experience (SOHO 2026) - "Interventions: After steroid prephase, dasatinib bridging was used (1 month) prior to ponatinib, until access approval...CNS prophylaxis included intrathecal triplet therapy with methotrexate, cytarabine, and dexamethasone, with a planned total of 15 administrations during ponatinib maintenance...In the CML blast phase patient, IGHV qPCR was not available; due to persistent BCR::ABL positivity, his treatment was supplemented with chemotherapy (hyperfractionated cyclophosphamide, vincristine, doxorubicin, dexamethasone), and he achieved a complete metabolic response and proceeded to transplant... Frontline blinatumomab plus ponatinib is a feasible chemotherapy-free strategy in Ph+ B-ALL, although limited by lack of first-line approval. Discordant MRD findings highlight the need for careful monitoring. Ongoing follow-up will determine durability of responses and whether allogeneic transplantation can be avoided in selected patients."

Clinical • Real-world • Real-world evidence • Acute Lymphocytic Leukemia • B Acute Lymphoblastic Leukemia • Chronic Myeloid Leukemia • Hematological Malignancies • Leukemia • Oncology • ABL1 • BCR • IGH

Outcomes of Consolidative Allogeneic Transplantation After Venetoclax Plus Hypomethylating Agent Induction in Acute Myeloid Leukemia: A Single-Center Retrospective Study (SOHO 2026) - "Induction consisted of VEN with 5-day decitabine (DEC) (VEN7/14-DEC5; n = 16, 66.7%) or 7-day azacitidine (VEN7/14-AZA7; n = 8, 33.3%), with a median of 2 cycles (range, 1–4) before allo-HSCT...One patient received ponatinib maintenance... In our cohort, allo-HSCT after VEN+HMA bridging demonstrated favorable outcomes despite a substantial proportion of patients being MRD-positive prior to transplantation. Transplantrelated mortality and graft-versus-host disease remain the key challenges. CR: complete response, CRi: CR with incomplete hematologic recovery, ECOG: Eastern Cooperative Oncology Group, ELN: European LeukemiaNet, GVHD: graft-versus-host disease, MAC: myeloablative conditioning, MFC: multiparameter flow cytometry, MLFS: morphologic leukemia-free state, MRD: minimal residual disease, MSD: matched sibling donors, RIC: reduced-intensity conditioning."

Retrospective data • Acute Myelogenous Leukemia • Hematological Malignancies • Leukemia • Myelodysplastic Syndrome • Oncology

ACHIEVEMENT OF MRD NEGATIVITY AFTER END OF INDUCTION WITH PONATINIB AND IMATINIB IN THE PHASE 3 PHALLCON TRIAL: A POST HOC ANALYSIS (EHA 2025) - P3 | "Pts who did not achieve MRD-neg by EOI and continued the study achieved deeper and more durable molecular responses with ponatinib than imatinib after C4D1; these pts also appeared to have better 2-year EFS with ponatinib than imatinib. These results support the clinical benefit and tolerability of continuing ponatinib in pts who have not achieved MRD-neg by EOI."

Minimal residual disease • P3 data • Retrospective data • Bone Marrow Transplantation • ABL1

Efficacy and Toxicity of Frontline Ponatinib Plus Blinatumomab for Adult Ph+ ALL Patients of All Ages. Intermediate Analysis of the Gimema ALL2820 (ASH 2024) - "In the previous GIMEMA LAL2116 trial, we showed the effectiveness of a chemo-free approach based on dasatinib followed by blinatumomab (Foà et al, NEJM 2020), with long-term (median follow-up 53 months) overall survival (OS) and disease-free survival (DFS) of 80.7% and 75.8%, respectively (Foà et al, JCO 2023). The combination was overall well tolerated, with very few treatment discontinuations, also in the elderly, suggesting that a ponatinib dose adjustment according to age may prevent severe toxicities. Lastly, with the biology-driven transplant allocation only 12% of patients have been transplanted so far."

Clinical • Acute Lymphocytic Leukemia • Hematological Malignancies • Infectious Disease • Leukemia • Novel Coronavirus Disease • Oncology • Pneumonia • Respiratory Diseases • Septic Shock • ABL1 • IKZF1

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

Primary efficacy analysis of phase II study investigating tyrosine kinase inhibitor (TKI) and inotuzumab ozogamicin-based therapy for newly diagnosed Philadelphia-chromosome positive acute lymphoblastic leukemia (Ph+ ALL) (ASH 2025) - "Tyrosine kinase inhibitor (TKI) + blinatumomab regimenshave demonstrated high MR4 rates and favorable overall survival (OS); however, these regimens includeup to 5 courses of blinatumomab which is a continuous 28-day infusion (Kantarjian et al, JCO 2024; Foa etal, JCO 2024)...Eligibilitycriteria includes newly diagnosed Ph+ ALL, age ≥ 18, ECOG ≤2, CD22+ on ≥20% blasts, and no centralnervous system (CNS) disease.Schema 1 was as follows; Course (C) 1 was (28 days) dasatinib (DAS) 140mg daily, dexamethasone (dex)10mg/m2 D1-7 & D15-21, and InO 0.8mg/m2 D8, 0.5mg/m2 D15 and D22...If MR4 was not achieved by end of C2 (EOC2), DAS was switched to ponatinib(PON)...TKI + InO-based therapy for newly diagnosed pts with Ph+ ALL has an MR3+ rate of 81% within 2 coursesand 100% of pts achieved MR4 and/or NGS MRD- disease by EOC3. No cases of VOD were seen withSchema 2. Given the excellent rates of MR3+ with limited cycles of InO, further development of thisinduction approach is..."

Clinical • P2 data • Acute Lymphocytic Leukemia • CNS Disorders • Hematological Malignancies • Hepatology • Infectious Disease • Leukemia • Pulmonary Disease • Respiratory Diseases • Septic Shock • IKZF1

Co-Existing Myeloid Mutations at Diagnosis Are Associated With Increased Tyrosine Kinase Inhibitor Utilization in Chronic Phase CML (SOHO 2026) - "Imatinib exposure was more common in the mutation-positive cohort (83.3% vs 60.2%; P = 0.03), and all imatinib-exposed mutation-positive patients discontinued imatinib compared with 81.3% of mutation-negative patients (P = 0.04). Use of ponatinib, a third-generation TKI often reserved for resistant or high-risk disease, was also significantly higher among mutation-positive patients (41.7% vs 13.5%; P < 0.001). Patients with co-existing myeloid mutations appeared to experience a more complex therapeutic course characterized by increased TKI switching and need for later-generation TKIs. ASXL1: additional sex combs like 1; BCR::ABL1: breakpoint cluster region:: ABL proto-oncogene 1; DNMT3A: DNA methyltransferase 3 alpha); IQR: interquartile range; MMR: major molecular response; TKI: tyrosine kinase inhibitor; TET2: tet methylcytosine dioxygenase 2; TP53: tumor protein p53."

Chronic Myeloid Leukemia • Hematological Malignancies • Leukemia • Oncology • ABL1 • ASXL1 • BCR • DNMT3A • TET2 • TP53

Comparison between Dasatinib-Blinatumomab Vs Ponatinib-Blinatumomab Chemo-Free Strategy for Newly Diagnosed Ph+ Acute Lymphoblastic Leukemia Patients. Preliminary Results of the Gimema ALLL2820 Trial (ASH 2023) - "So far, the benefit of the current protocol appears to rely on a lower relapse rate, with only 1 relapse being observed to date, while in the same time period 3 relapses were documented with the dasatinib-blinatumomab combination. Further details will be provided."

Clinical • Acute Lymphocytic Leukemia • Hematological Malignancies • Infectious Disease • Leukemia • Oncology • Pneumonia • Respiratory Diseases • CD19 • IKZF1

First results of the Phase III GIMEMA ALL2820 trial comparing ponatinib plus blinatumomab to imatinib and chemotherapy for newly diagnosed adult ph+ acute lymphoblastic leukemia patients (ASH 2025) - "Compared to the GIMEMA LAL2116 trial, anincrease in MRD negativity and less relapses were observed. A chemo-free approach should be the newstandard for adult Ph+ ALL."

Clinical • IO biomarker • P3 data • Acute Lymphocytic Leukemia • Cardiovascular • Hematological Disorders • Hematological Malignancies • Infectious Disease • Leukemia • Myocardial Infarction • Pneumonia • Renal Disease • Respiratory Diseases • Septic Shock • ABL1 • IKZF1

Safety and Efficacy of Tgrx-678, a Potent BCR::ABL1 allosteric Inhibitor, in Patients with Tyrosine Kinase Inhibitor Resistant and/or Intolerant Chronic Myeloid Leukemia: Updated Results of Phase 1 Study Tgrx-678 -1001 (ASH 2024) - P1, P2 | "Methods : In phase Ia, CML-CP and CML-AP patients who were R/I at least to imatinib, dasatinib and nilotinib were enrolled...Patients were heavily pretreated; 71 (66%) CP and 44 (88%) AP patients had received ≥ 3 prior TKIs; 40 (37%) CP and 30 (60%) AP patients had previously received ponatinib, olverembatinib, asciminib, and/or HS-10382 (a new STAMP inhibitor)...The updated data indicate promising efficacy in both CP and AP patients including those with the T315I mutation and those who failed 3G-TKI or STAMP inhibitors. Ongoing Phase 2 trials in China (NCT NCT06453902) and Phase 1 trials in US (NCT06088888) are further evaluating TGRX-678, underscoring the need for continued assessment."

Clinical • P1 data • Anemia • Chronic Myeloid Leukemia • Diabetes • Dyslipidemia • Hypertriglyceridemia • Leukopenia • Metabolic Disorders • Neutropenia • Thrombocytopenia • ABL1

Asciminib vs Dasatinib/Nilotinib as First-Line Tyrosine Kinase Inhibitor Therapy in Chronic Myeloid Leukemia: A Propensity Score-Matched Analysis of Disease Progression and Safety Outcomes (SOHO 2026) - "The primary end point was disease progression between days 90 and 270, defined as escalation to ponatinib or omacetaxine, hematopoietic stem cell transplantation, or transformation to acute leukemia. The progression difference did not reach statistical significance, partly reflecting insufficient power to detect a moderate effect. Retrospective claims-level ascertainment of progression is imperfect, as some therapy switches may not represent true disease advancement. The cytopenia reduction with asciminib was substantial and statistically significant."

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

Efficacy of Olverembatinib in Patients With Chronic-Phase Chronic Myeloid Leukemia With Prior Resistance to Ponatinib or Asciminib and ASXL1 Mutations (SOHO 2026) - "These data provide evidence of olverembatinib activity in ponatinib-/asciminib-resistant CP-CML, including patients with ASXL1 mutations. This agent may offer a therapeutic option for patients with relapsed/refractory CP-CML and challenging genotypes after multiple TKIs. ASXL1: ASXL transcriptional regulator 1, BCR:: ABL1: breakpoint cluster region–Abelson 1, TKI: tyrosine kinase inhibitor."

Clinical • Chronic Myeloid Leukemia • Hematological Malignancies • Leukemia • Oncology • ABL1 • ASXL1 • BCR

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

Venetoclax plus inotuzumab ozogamicin for relapsed and refractory ALL: Results of a phase I trial (ASH 2025) - P1 | "Due to distinct mechanisms of action and non-overlapping toxicities, we hypothesized that adding VEN to INO would be safe and effective. This investigator-sponsored phase I study (NCT05016947) enrolled pts ≥18 years with CD22+ (≥20% ofblasts) R/R ALL (≥5% bone marrow [BM] blasts) or lymphoblastic lymphoma (LBL, BM <5% blasts).Philadelphia chromosome-negative (Ph-) pts had received ≥1 line of therapy; Ph+ pts were ponatinib(PON)-refractory or ineligible...Dexamethasone (10 mg/m2) was given during Lead-In and D1-4 of C1 Induction...BH3 profiling showed that ptsMRD- by C2 had lower pre-treatment mitochondrial apoptotic priming.Of the 21 CR patients, 1 pt (KMT2Ar) progressed during C2, and the remaining 20 pts (95.2%) wereconsolidated with blinatumomab (n=9, 42.9%), SCT (n=14, 66.7%, 6 after blinatumomab), DLI (n=1), XRT(n=1), or POMP (n=1)... VEN can be safely added to INO in pts with R/R CD22+ ALL/LBL including Ph+ ALL, with a very high anddurable rate of MRD- CR...."

P1 data • CNS Disorders • Febrile Neutropenia • Gastrointestinal Disorder • Hepatology • Lymphoblastic Lymphoma • Lymphoma • Neutropenia • Thrombocytopenia • KMT2A

Randomized comparison of ponatinib versus imatinib in combination with chemotherapy in patients 55 years of age and older with newly diagnosed ph+ ALL: Molecular response and initial outcome analysis of the EWALL PH03 Study (ASH 2025) - P2 | "Moreover, the bispecific T-cell engager blinatumomab (BLIN) hasemerged as a potent front-line modality in Ph+ALL. In older pts with Ph+ALL receiving upfront reduced-intensity chemotherapy (EWALL), PONinduces a higher, albeit not significant, deep molecular response rate compared to IM, The safety profileof PON was consistent with known AEs and did not lead to a higher rate of withdrawals from studytreatment than IM. The impact on survival will require longer follow-up."

Clinical • Combination therapy • Acute Lymphocytic Leukemia • Hypertension • Pancreatitis • Thrombosis • ABL1 • BCR

A Novel BCR::ABL1 I502 T Mutation Associated With Acquired Asciminib Resistance in Chronic-Phase Chronic Myeloid Leukemia (SOHO 2026) - "Case: A 41-year-old woman with CP-CML was initially treated with imatinib for 5 years before transitioning to nilotinib for molecular relapse...Critically, I502 T retained sensitivity to dasatinib (IC50 0.3 nM) and ponatinib (IC50 0.7 nM)... I502 T is a novel myristoyl pocket mutation that confers high-level asciminib resistance while retaining sensitivity to ATP-competitive TKIs, further expanding the landscape of resistance at this critical drug-binding interface. ATP: adenosine triphosphate, BCR::ABL1: breakpoint cluster region–Abelson murine leukemia viral oncogene homolog 1, ERK: extracellular signal-regulated kinase, IC50: half-maximal inhibitory concentration, S6: ribosomal protein S6, STAT5: signal transducer and activator of transcription 5, VAF: variant allele frequency, WT: wild-type."

Chronic Myeloid Leukemia • Hematological Malignancies • Leukemia • Oncology • ABL1 • BCR • RPS6 • STAT5

Dose-adjusted etoposide, prednisone, vincristine, cyclophosphamide, and doxorubicin (DA-EPOCH) yields durable remissions and survival in adults with newly diagnosed acute lymphoblastic leukemia/lymphoma (ALL): Long-term follow-up of a prospective trial (ASH 2025) - P2 | "In a single-arm Phase II trial weconducted, DA-EPOCH ± rituximab (R) ± TKI yielded comparable morphologic (morph) and measurableresidual disease (MRD)- remissions with less toxicity than seen in a comparable cohort of patientsreceiving hyperCVAD. This study completed accrual in 2021, before routine upfront incorporation ofimmunotherapy and ponatinib (if Ph+)...Imatinib or dasatinib was added if Ph+, and R if CD20+...8 pts (15%) switched to blinatumomab whenMRD+ after DA-EPOCH, with none receiving it when MRD-. DA-EPOCH±R±TKI yields durable remissions, with survival comparable toimmunotherapy-based strategies for ALL... DA-EPOCH±R±TKI yields durable remissions, with survival comparable toimmunotherapy-based strategies for ALL. Unlike many other approaches, outcomes for older pts weresimilar to the general study population. These results support DA-EPOCH±R±TKI as a curative-intentoption, particularly in resource-limited settings."

Clinical • Acute Lymphocytic Leukemia • Hematological Malignancies • Leukemia • Lymphoma • ABL1 • CD20

Results of ponatinib as frontline therapy for chronic myeloid leukemia in chronic phase. (PubMed, Cancer) - "Ponatinib yielded high cytogenetic and molecular responses in newly diagnosed chronic myeloid leukemia in chronic phase. Its use in the frontline setting is hindered by arterio-/vaso-occlusive and other severe toxicities."

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

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

A phase 2 study of the combination of decitabine (DAC), venetoclax (VEN), and ponatinib in patients (Pts) with chronic myeloid leukemia (CML) in accelerated phase (AP)/myeloid blast phase (MBP) or Philadelphia-chromosome positive (Ph+) acute myeloid leukemia (AML). (ASCO 2023) - P2 | "Intrathecal prophylaxis with 4 doses of cytarabine was recommended. A triplet combination of DAC, VEN and ponatinib was well-tolerated and resulted in an ORR of 73% in this poor-risk population of pts with advanced Ph+ leukemias. Clinical trial information: NCT04188405. >"

Clinical • P2 data • Acute Myelogenous Leukemia • Bone Marrow Transplantation • Cardiovascular • Chronic Myeloid Leukemia • Hematological Malignancies • Infectious Disease • Leukemia • Mucositis • Oncology • Transplantation • ABL1

Trial of Imatinib after Ponatinib Induction (TIPI) in the Front-Line Treatment of Chronic Phase (CP) Chronic Myeloid Leukemia (CML) Setting. Report of the First Therapeutic Sequence (ASH 2023) - P2 | "Ponatinib displays high anti-leukemic activity as front-line therapy in selected newly diagnosed CP-CML pts with high early molecular response rates with non-negligible severe –in particular cardio-vascular- toxicity at 30 mg QD. Whether or not this will be translated into substantial TFR rates will be determined at later time points."

Cardiovascular • Chronic Myeloid Leukemia • Diabetes • Hematological Malignancies • Hypertension • Infectious Disease • Metabolic Disorders • Pulmonary Embolism • Respiratory Diseases • ABL1

A Phase I Study of Asciminib (ABL001) in Combination with Dasatinib and Prednisone for BCR-ABL1-Positive ALL and Blast Phase CML in Adults (ASH 2023) - P1 | "Both patients with imatinib-refractory CML-LBC progressed (C9, C3). Of those with ALL, 8 bridged to SCT after 2-8 cycles; 2 elected local care (C5, C7); 1 transitioned to ponatinib for inadequate response plus recurrent DAS pulmonary toxicity (C4); 6 remained on study treatment until disease progression (C4 – MRD+, C45, C11, C11); 3 remain on study... Dual ABL1 kinase inhibition with ASC and DAS plus pred in BCR::ABL1+ ALL and CML-LBC is feasible and tolerable in adults with BCR::ABL1+ ALL and CML-LBC. DLTs at ASC 160 mg/d were asymptomatic amylase and lipase elevation, without clinical sequelae. ASC 80 mg/day was declared the RP2D, and an expansion cohort of 10 pts was completed."

Clinical • Combination therapy • P1 data • Acute Lymphocytic Leukemia • B Acute Lymphoblastic Leukemia • Chronic Myeloid Leukemia • CNS Disorders • Hematological Malignancies • Leukemia • Oncology • Pancreatitis • ABL1 • BCR