^
    6d
    The Efficacy and Safety of Third-generation TKIs Combined With Azacitidine and Bcl-2 Inhibitor in Patients With CML-MBP (clinicaltrials.gov)
    P=N/A, N=30, Not yet recruiting, Peking University People's Hospital
    New trial
    |
    BCL2 (B-cell CLL/lymphoma 2)
    |
    Venclexta (venetoclax) • Iclusig (ponatinib) • azacitidine • Nailike (olverembatinib)
    7d
    Asciminib for third-line treatment of chronic myeloid leukemia: Cost-effectiveness analysis based on treatment-free remission approach. (PubMed, Farm Hosp)
    Asciminib broadens therapeutic choices for patient's refractory or intolerant to 2 prior lines of treatment in a cost-effectiveness manner. The costs of drugs significantly impact the overall cost of the disease, emphasizing the importance of the selected discount rates for each drug. Given the relatively low incidence of CML, the introduction of asciminib has a limited budgetary impact, warranting individualized decisions based on patient`s clinical characteristics.
    Journal • HEOR • Cost-effectiveness • Cost effectiveness
    |
    ABL1 (ABL proto-oncogene 1) • BCR (BCR Activator Of RhoGEF And GTPase)
    |
    BCR-ABL1 fusion
    |
    imatinib • Iclusig (ponatinib) • Bosulif (bosutinib) • Scemblix (asciminib)
    8d
    Ponatinib Induces a Procoagulant Phenotype in Human Coronary Endothelial Cells via Inducing Apoptosis. (PubMed, Pharmaceutics)
    In addition, these changes were associated with an increased ratio of Bax and Bcl-xL proteins in the presence of the decreased THBD mRNA level. Overall, ponatinib enhances the procoagulant activity of ECs via inducing apoptosis, which may contribute to thrombotic events.
    Journal
    |
    ABL1 (ABL proto-oncogene 1) • BCR (BCR Activator Of RhoGEF And GTPase) • BCL2L1 (BCL2-like 1) • VCAM1 (Vascular Cell Adhesion Molecule 1)
    |
    Iclusig (ponatinib)
    22d
    Asciminib Maintains Antibody-Dependent Cellular Cytotoxicity against Leukemic Blasts. (PubMed, Cancers (Basel))
    The introduction of rituximab has improved the outcomes in CD20 positive cases. Other monoclonal antibodies, such as tafasitamab (anti-CD19), obinutuzumab (anti-CD20) and epratuzumab (anti-CD22) have been tested in trials (NCT05366218, NCT04920968, NCT00098839)...In contrast to ATP site inhibitors such as dasatinib and ponatinib, the novel first-in-class selective allosteric ABL myristoyl pocket (STAMP) inhibitor asciminib did not significantly impact ADCC in our settings. Our results suggest that asciminib should be considered in clinical trials.
    Journal
    |
    ABL1 (ABL proto-oncogene 1) • BCR (BCR Activator Of RhoGEF And GTPase)
    |
    BCR-ABL1 fusion • CD20 positive
    |
    dasatinib • Rituxan (rituximab) • Iclusig (ponatinib) • Gazyva (obinutuzumab) • Scemblix (asciminib) • Monjuvi (tafasitamab-cxix) • Epratucyn (epratuzumab)
    26d
    Ponatinib and STAT5 Inhibitor Pimozide Combined Synergistic Treatment Applications Potentially Overcome Drug Resistance via Regulating the Cytokine Expressional Network in Chronic Myeloid Leukemia Cells. (PubMed, J Interferon Cytokine Res)
    Therefore, pimozide could be a promising agent to support TKI therapies in ponatinib resistance. This research would help to clarify the role of cytokines in ponatinib resistance and advance the development of new therapeutics to utilize the STAT5 inhibitor pimozide in combination with TKIs.
    Journal
    |
    ABL1 (ABL proto-oncogene 1) • BCR (BCR Activator Of RhoGEF And GTPase) • IFNG (Interferon, gamma) • IL6 (Interleukin 6) • CXCL8 (Chemokine (C-X-C motif) ligand 8) • IL2 (Interleukin 2) • IL10 (Interleukin 10) • IL18 (Interleukin 18) • IL1A (Interleukin 1, alpha) • IL15 (Interleukin 15) • STAT5A (Signal Transducer And Activator Of Transcription 5A)
    |
    Iclusig (ponatinib)
    1m
    Characterization of Asciminib-Resistant Philadelphia Chromosome-Positive Cells. (PubMed, World J Oncol)
    Y139D and T315I mutations are extremely resistant to asciminib. Ponatinib and omacetaxine show potential for treating asciminib-resistant chronic myeloid leukemia.
    Journal
    |
    ABL1 (ABL proto-oncogene 1)
    |
    ABL1 T315I
    |
    Iclusig (ponatinib) • Scemblix (asciminib) • Synribo (omacetaxine mepesuccinate)
    1m
    A New Algorithm Integrating Molecular Response, Toxicity, and Plasma Level Measures for Ponatinib Dose Choice in Patients Affected by Chronic Myeloid Leukemia. (PubMed, Pharmaceutics)
    In a real-world setting, adjustment of ponatinib daily doses lower than those registered may maintain therapeutic efficacy while reducing the risk of vascular events and improving tolerability. Further studies are warranted to confirm the present results in a larger cohort of patients.
    Journal
    |
    ABL1 (ABL proto-oncogene 1) • BCR (BCR Activator Of RhoGEF And GTPase)
    |
    Iclusig (ponatinib)
    2ms
    Potential protein kinase inhibitors that target G-quadruplex DNA structures in the human telomeric regions. (PubMed, Mol Divers)
    Thus, it is hypothesized that Ponatinib and Lapatinib may stabilize human telomeric G4 DNA in addition to their ability to inhibit BCR-ABL and the other members of the EGFR family. As a result, we also hypothesize that the stabilization of G4 DNA might represent an additional underlying mechanism contributing to their efficacy in exerting anti-cancer effects.
    Journal
    |
    EGFR (Epidermal growth factor receptor) • ABL1 (ABL proto-oncogene 1) • BCR (BCR Activator Of RhoGEF And GTPase)
    |
    lapatinib • Iclusig (ponatinib)
    2ms
    Serial Measurements of Molecular and Architectural Responses to Therapy (SMMART) PRIME Trial (clinicaltrials.gov)
    P1, N=2, Terminated, OHSU Knight Cancer Institute | Active, not recruiting --> Terminated; Low accrual
    Trial termination
    |
    Keytruda (pembrolizumab) • Opdivo (nivolumab) • Avastin (bevacizumab) • Venclexta (venetoclax) • Lynparza (olaparib) • Mekinist (trametinib) • erlotinib • Gilotrif (afatinib) • Yervoy (ipilimumab) • Ibrance (palbociclib) • dasatinib • Zelboraf (vemurafenib) • Tafinlar (dabrafenib) • carboplatin • Imfinzi (durvalumab) • sorafenib • Rozlytrek (entrectinib) • imatinib • sunitinib • everolimus • Nerlynx (neratinib) • Iclusig (ponatinib) • Kadcyla (ado-trastuzumab emtansine) • Cotellic (cobimetinib) • Lorbrena (lorlatinib) • Lenvima (lenvatinib) • bortezomib • doxorubicin hydrochloride • capecitabine • Verzenio (abemaciclib) • Xtandi (enzalutamide capsule) • Cabometyx (cabozantinib tablet) • albumin-bound paclitaxel • Stivarga (regorafenib) • abiraterone acetate • oxaliplatin • Aliqopa (copanlisib) • Vizimpro (dacomitinib) • Zydelig (idelalisib) • daunorubicin • Zolinza (vorinostat) • Idhifa (enasidenib) • Farydak (panobinostat) • Erivedge (vismodegib) • Nubeqa (darolutamide) • bicalutamide • leucovorin calcium • cabazitaxel • Vesanoid (tretinoin) • fluorouracil topical
    2ms
    A Study of Ponatinib With Chemotherapy in Children, Teenagers, and Adults With Philadelphia Chromosome-Positive Acute Lymphoblastic Leukemia (clinicaltrials.gov)
    P1/2, N=68, Active, not recruiting, Takeda | Trial completion date: Aug 2027 --> Jan 2027 | Recruiting --> Active, not recruiting
    Enrollment closed • Trial completion date
    |
    ABL1 (ABL proto-oncogene 1) • BCR (BCR Activator Of RhoGEF And GTPase) • IGH (Immunoglobulin Heavy Locus) • PDGFRB (Platelet Derived Growth Factor Receptor Beta) • CSF1R (Colony stimulating factor 1 receptor) • PIAS4 (Protein Inhibitor Of Activated STAT 4)
    |
    BCR-ABL1 fusion • BCR-ABL1 T315I • ABL1 T315I • BCR-ABL1 mutation
    |
    cytarabine • Iclusig (ponatinib) • cyclophosphamide
    2ms
    NCI-2018-01078: Blinatumomab, Methotrexate, Cytarabine, and Ponatinib in Treating Patients With Philadelphia Chromosome-Positive, or BCR-ABL Positive, or Relapsed/Refractory, Acute Lymphoblastic Leukemia (clinicaltrials.gov)
    P2, N=90, Recruiting, M.D. Anderson Cancer Center | Trial completion date: Nov 2024 --> Nov 2025 | Trial primary completion date: Nov 2024 --> Nov 2025
    Trial completion date • Trial primary completion date
    |
    ABL1 (ABL proto-oncogene 1) • BCR (BCR Activator Of RhoGEF And GTPase)
    |
    cytarabine • Iclusig (ponatinib) • Blincyto (blinatumomab) • methotrexate • Starasid (cytarabine ocfosfate)
    2ms
    Pharmacovigilance study of BCR-ABL1 tyrosine kinase inhibitors: a safety analysis of the FDA adverse event reporting system. (PubMed, BMC Pharmacol Toxicol)
    The results of this study demonstrated that AE signals differ among the five BCR-ABL1 TKIs. Furthermore, each BCR-ABL1 TKI displayed several new signals. These findings provide valuable information for clinicians aiming to reduce the risk of AEs during BCR-ABL1 TKI treatment.
    Journal • Adverse events
    |
    ABL1 (ABL proto-oncogene 1) • BCR (BCR Activator Of RhoGEF And GTPase)
    |
    dasatinib • imatinib • Iclusig (ponatinib) • Tasigna (nilotinib) • Bosulif (bosutinib)
    2ms
    Navigating the Management of Chronic Phase CML in the Era of Generic BCR::ABL1 Tyrosine Kinase Inhibitors. (PubMed, J Natl Compr Canc Netw)
    They include the broader availability of cost-effective generic imatinib, and soon other generic second-generation tyrosine kinase inhibitors (TKIs). For asciminib, longer-term follow-up is needed to better evaluate its safety and efficacy compared with ponatinib. Allogeneic stem cell transplantation represents a valid alternative to newer-generation TKIs, with a better treatment value when TKIs are priced at >$40,000/year.
    Review • Journal
    |
    ABL1 (ABL proto-oncogene 1)
    |
    imatinib • Iclusig (ponatinib) • Scemblix (asciminib)
    2ms
    A Phase II Study of the Combination of Ponatinib With Mini-hyper CVD Chemotherapy and Venetoclax in Patients With Relapsed or Refractory T-cell Acute Lymphoblastic Leukemia (clinicaltrials.gov)
    P2, N=26, Recruiting, M.D. Anderson Cancer Center | Active, not recruiting --> Recruiting
    Enrollment open
    |
    BCL2 (B-cell CLL/lymphoma 2)
    |
    Venclexta (venetoclax) • Iclusig (ponatinib)
    2ms
    Pediatric-Inspired Chemotherapy Plus Tyrosine Kinase Inhibitor in Adult Philadelphia Chromosome-Positive Acute Lymphoblastic Leukemia (clinicaltrials.gov)
    P2, N=0, Withdrawn, University of Michigan Rogel Cancer Center | N=23 --> 0 | Recruiting --> Withdrawn
    Enrollment change • Trial withdrawal
    |
    ABL1 (ABL proto-oncogene 1) • BCR (BCR Activator Of RhoGEF And GTPase)
    |
    dasatinib • cytarabine • Iclusig (ponatinib) • doxorubicin hydrochloride • cyclophosphamide
    3ms
    Decitabine, Venetoclax, and Ponatinib for the Treatment of Philadelphia Chromosome-Positive Acute Myeloid Leukemia or Myeloid Blast Phase or Accelerated Phase Chronic Myelogenous Leukemia (clinicaltrials.gov)
    P2, N=30, Active, not recruiting, M.D. Anderson Cancer Center | Recruiting --> Active, not recruiting
    Enrollment closed • IO biomarker
    |
    ABL1 (ABL proto-oncogene 1) • BCR (BCR Activator Of RhoGEF And GTPase) • BCL2 (B-cell CLL/lymphoma 2)
    |
    BCL2 expression
    |
    Venclexta (venetoclax) • Iclusig (ponatinib) • decitabine
    3ms
    A Phase II Study of the Combination of Ponatinib With Mini-hyper CVD Chemotherapy and Venetoclax in Patients With Relapsed or Refractory T-cell Acute Lymphoblastic Leukemia (clinicaltrials.gov)
    P2, N=3, Active, not recruiting, M.D. Anderson Cancer Center | Recruiting --> Active, not recruiting | N=20 --> 3
    Enrollment closed • Enrollment change
    |
    BCL2 (B-cell CLL/lymphoma 2)
    |
    Venclexta (venetoclax) • Iclusig (ponatinib)
    3ms
    Integrated Stress Response Potentiates Ponatinib-Induced Cardiotoxicity. (PubMed, Circ Res)
    The findings that compromised ATP production potentiates GCN2-mediated ISR activation have broad implications across various cardiac diseases. Our results also highlight an unanticipated role of ponatinib in causing direct activation of a kinase target despite its role as an ATP-competitive kinase inhibitor.
    Journal
    |
    ATF4 (Activating Transcription Factor 4) • TCF4 (Transcription Factor 4)
    |
    Iclusig (ponatinib)
    4ms
    A Study to Investigate LP-118, Ponatinib, Vincristine and Dexamethasone in Relapsed/Refractory Acute Lymphoblastic Leukemia (ALL) or Lymphoblastic Lymphoma (LBL) (clinicaltrials.gov)
    P1/2, N=33, Not yet recruiting, University of Chicago
    New P1/2 trial
    |
    Iclusig (ponatinib) • vincristine • Xatmep (methotrexate oral solution)
    4ms
    NCI-2018-01186: Low-Intensity Chemotherapy, Ponatinib and Blinatumomab in Treating Patients With Philadelphia Chromosome-Positive and/or BCR-ABL Positive Acute Lymphoblastic Leukemia (clinicaltrials.gov)
    P2, N=21, Active, not recruiting, M.D. Anderson Cancer Center | Trial completion date: Feb 2024 --> Feb 2025 | Trial primary completion date: Feb 2024 --> Feb 2025
    Trial completion date • Trial primary completion date
    |
    ABL1 (ABL proto-oncogene 1) • BCR (BCR Activator Of RhoGEF And GTPase)
    |
    Rituxan (rituximab) • cytarabine • Iclusig (ponatinib) • cyclophosphamide • Blincyto (blinatumomab) • methotrexate • vincristine • Neulasta (pegfilgrastim) • Neupogen (filgrastim) • Starasid (cytarabine ocfosfate)
    4ms
    Pona-CELL: Ponatinib Plus Reduced-intensity Chemotherapy in the First-line Treatment of Adult Patients With Ph+ ALL (clinicaltrials.gov)
    P2, N=32, Suspended, Institute of Hematology and Blood Transfusion, Czech Republic | Trial completion date: Sep 2026 --> Jul 2024 | Active, not recruiting --> Suspended | Trial primary completion date: Sep 2024 --> Sep 2023
    Trial completion date • Trial suspension • Trial primary completion date
    |
    ABL1 (ABL proto-oncogene 1) • BCR (BCR Activator Of RhoGEF And GTPase)
    |
    Iclusig (ponatinib)
    4ms
    Ponatinib Improved the Prognosis of Philadelphia Chromosome-Positive Acute Lymphoblastic Leukemia: A Japanese Single-Center Cohort Study. (PubMed, Cureus)
    Results Twenty-three patients with Ph+ALL were treated with intensive chemotherapy combined with TKI, including six imatinib, four dasatinib, and 13 ponatinib. Patients with CMR within three months might not necessarily need to receive HSCT, but a subsequent treatment-free status could have been achieved only by HSCT. Furthermore, CD20 positivity may be a useful biomarker for future treatment decisions in patients with Ph+ALL.
    Journal
    |
    CD20 (Membrane Spanning 4-Domains A1)
    |
    CD20 positive
    |
    dasatinib • imatinib • Iclusig (ponatinib)
    4ms
    SOHO State of the Art Updates and Next Questions: Update on the Approach to Philadelphia Chromosome-Positive Acute Lymphoblastic Leukemia. (PubMed, Clin Lymphoma Myeloma Leuk)
    Treatment with blinatumomab and ponatinib resulted in a CMR rate of 84%, a 2-year event-free survival (EFS) of 78%, and a 2-year OS rate of 90%; only 1 patient underwent HSCT. Achieving NGS MRD negativity can also identify patients who may have durable remissions with a low risk of relapse. Herein, we discuss the current approach to the management of adults with Ph-positive ALL, the role of HSCT, MRD monitoring, and future therapies.
    Review • Journal
    |
    ABL1 (ABL proto-oncogene 1)
    |
    Iclusig (ponatinib) • Blincyto (blinatumomab)
    4ms
    Study to Evaluate the Reinduction and Second Stop of TKI With Ponatinib in CML in Molecular Response (ResToP) (clinicaltrials.gov)
    P2, N=80, Active, not recruiting, Fundacion CRIS de Investigación para Vencer el Cáncer | Trial completion date: Dec 2024 --> Dec 2025 | Trial primary completion date: Dec 2024 --> Dec 2025
    Trial completion date • Trial primary completion date
    |
    ABL1 (ABL proto-oncogene 1) • BCR (BCR Activator Of RhoGEF And GTPase)
    |
    Iclusig (ponatinib)
    4ms
    How to Manage Philadelphia-Positive Acute Lymphoblastic Leukemia in Resource-Constrained Settings. (PubMed, Cancers (Basel))
    The T315I mutation is the most common mechanism for disease resistance, being targetable to ponatinib. Blinatumomab, a bispecific antibody, has shown significant synergy with TKIs in treating this disease. It serves as an excellent salvage therapy, aside from achieving outstanding results when incorporated into the frontline.
    Review • Journal
    |
    ABL1 (ABL proto-oncogene 1) • BCR (BCR Activator Of RhoGEF And GTPase) • IKZF1 (IKAROS Family Zinc Finger 1)
    |
    ABL1 T315I
    |
    Iclusig (ponatinib) • Blincyto (blinatumomab)
    5ms
    Promoter swapping of truncated PDGFRB drives Ph-like acute lymphoblastic leukemia. (PubMed, NPJ Precis Oncol)
    We confirmed the oncogenic potential of NRIP1::PDGFRB in vitro and the efficacy of all ABL1-specific inhibitor generations, including imatinib, dasatinib, nilotinib, and ponatinib, in suppressing this potential. PDGFRB activation mechanism may include juxtamembrane domain truncation in the predicted peptide. In conclusion, we determined a novel fusion gene pattern in Ph-like ALL.
    Journal
    |
    ABL1 (ABL proto-oncogene 1) • PDGFRB (Platelet Derived Growth Factor Receptor Beta)
    |
    PDGFRB fusion
    |
    dasatinib • imatinib • Iclusig (ponatinib) • Tasigna (nilotinib)
    5ms
    Resistance mutations in CML and how we approach them. (PubMed, Hematology Am Soc Hematol Educ Program)
    Each of the 5 ATP-competitive inhibitors (imatinib, dasatinib, nilotinib, bosutinib, ponatinib) has a well-defined spectrum of resistance mutations. Growing clinical experience will soon allow to also elucidate the full spectrum of mutations conferring resistance to asciminib (that appear not to be confined to the myristate binding pocket)...Novel technologies like next-generation sequencing and digital polymerase chain reaction have recently been explored for BCR::ABL1 KD mutation testing; they have both advantages and disadvantages that are discussed in this article. This review also provides suggestions for interpretation and clinical translation of mutation testing results, which may not always be straightforward, particularly in cases of low-level or unknown mutations.
    Journal
    |
    ABL1 (ABL proto-oncogene 1)
    |
    dasatinib • imatinib • Iclusig (ponatinib) • Tasigna (nilotinib) • Bosulif (bosutinib) • Scemblix (asciminib)
    5ms
    Accelerated-phase CML: de novo and transformed. (PubMed, Hematology Am Soc Hematol Educ Program)
    The development of novel treatment strategies such as the MATCHPOINT approach for BP-CML, utilizing combination chemotherapy with fludarabine, cytarabine, and idarubicin in addition to dose-modified ponatinib, may also be an important step in improving treatment outcomes. However, identifying patients who are high risk of transformation remains a challenge, and the recent 2022 updates to the international guidelines may add further confusion to this area. Further work is required to clarify the identification and treatment strategy for the patients who require a more aggressive approach than standard chronic phase CML management.
    Journal
    |
    ABL1 (ABL proto-oncogene 1)
    |
    cytarabine • Iclusig (ponatinib) • idarubicin hydrochloride • fludarabine IV
    5ms
    CXCR2 inhibition overcomes ponatinib intolerance by eradicating chronic myeloid leukemic stem cells through PI3K/Akt/mTOR and dipeptidylpeptidase Ⅳ (CD26). (PubMed, Heliyon)
    Treatment with the CXCR2 antagonist, SB225002, effectively curtails cell proliferation and triggers apoptosis in ponatinib-resistant CML cells. These findings underscore the novel role of CXCR2 in the regulation of not only ponatinib-resistant CML cells, but also CML leukemic stem cells. Consequently, our study proposes that targeting CXCR2 holds promise as a viable therapeutic strategy for addressing patients with CML grappling with ponatinib resistance.
    Journal
    |
    CXCR2 (Chemokine (C-X-C motif) receptor 2) • DPP4 (Dipeptidyl Peptidase 4)
    |
    Iclusig (ponatinib) • SB225002
    5ms
    Equity and Resource Allocation: The Case for Allogeneic Transplant in Emergency Medicaid Patients (ASH 2023)
    He began maintenance BCNU/cytoxan, then several cycles 6-MP/MTX/vincristine. On day +554 after diagnosis, he relapsed and started decitabine/venetoclax, then decadron + dasatinib, then MVP, followed by 3 cycles of inotuzumab...As his condition worsened he was put on ponatinib, then asciminib before expiring on day +940...On day +447 he started blinatumomab + IT MTX + nilotinib...The patient underwent leukapheresis and started HiDAC + mitoxantrone + etoposide + dasatinib...Likewise, many undocumented adults are the parents of US citizen minors who would benefit economically from their survival. For consideration we will explore cost analysis to further elucidate the potential benefit of allowing coverage of HSCT.
    Reimbursement • US reimbursement • HEOR • Medicaid
    |
    ABL1 (ABL proto-oncogene 1) • BCR (BCR Activator Of RhoGEF And GTPase)
    |
    Venclexta (venetoclax) • dasatinib • Iclusig (ponatinib) • Tasigna (nilotinib) • cyclophosphamide • etoposide IV • Blincyto (blinatumomab) • decitabine • Besponsa (inotuzumab ozogamicin) • vincristine • mitoxantrone • Scemblix (asciminib)
    5ms
    Asciminib Enhances Its Treatment Efficacy Synergistically in the Treatment of Chronic Myeloid Leukemia Harboring ABL1 Kinase Domain Mutation When Combined with a Reduced Dose of Ponatinib, Dasatinib, or Bosutinib, but Not with Nilotinib or Imatinib (ASH 2023)
    The present study demonstrated that a half of baseline conc ABPIs in combination with ASC is as effective as other ABPIs not just in WT but also in other ABL1 KDM CML cell lines. Different CML cell lines harboring different ABL KDM has different treatment spectrum on optimal ABPI drug as well as optimal drug conc. This result will be useful to design future clinical trial of dual blockade of ASC with other ABPIs considering the ABL KDM profiles.
    Clinical
    |
    ABL1 (ABL proto-oncogene 1) • BCR (BCR Activator Of RhoGEF And GTPase)
    |
    BCR-ABL1 E255K • BCR-ABL1 F317L • BCR-ABL1 G250E • BCR-ABL1 M244V • ABL1 T315I • BCR-ABL1 M351T • BCR-ABL1 H396P • BCR-ABL1 Y253F • BCR-ABL1 F317V • ABL1 E255K • BCR-ABL1 T315A • ABL1 F317L • ABL1 G250E • ABL1 M351T
    |
    dasatinib • imatinib • Iclusig (ponatinib) • Tasigna (nilotinib) • Bosulif (bosutinib) • Scemblix (asciminib)
    5ms
    Biological Factors Associated with Treatment-Free Remission in Clinical Practice: Data from the Canarian Registry of CML (ASH 2023)
    51% of patients (n=56) discontinued from imatinib, 31% from nilotinib (n=34), 16% from dasatinib (n=17), and 1% from bosutinib and ponatinib (1 patient each). We confirmed previous observations that the biological factors BCR: : ABL1 positivity at stop and longer HT were associated with molecular relapse although no difference was found for short HT. The impact of clinical factors on TFR, including duration of MR4 and MR4. 5 prior to stop, were also confirmed in our real-life series with a long follow-up, while total TKI duration was not prognostic.
    Clinical
    |
    ABL1 (ABL proto-oncogene 1) • DNMT3A (DNA methyltransferase 1) • ASXL1 (ASXL Transcriptional Regulator 1) • TET2 (Tet Methylcytosine Dioxygenase 2)
    |
    DNMT3A mutation • ASXL1 mutation • TET2 mutation
    |
    dasatinib • imatinib • Iclusig (ponatinib) • Tasigna (nilotinib) • Bosulif (bosutinib)
    5ms
    Efficacy and Safety of Asciminib in Chinese Patients with Philadelphia Chromosome(Ph)-Positive Leukaemias (ASH 2023)
    Its efficacy and safety profile in patients with chronic-phase chronic myeloid leukaemia (CML) have been shown in the Phase 3 ASCEMBL study, comparing asciminib 40 mg twice daily versus bosutinib 500 mg once daily...All had received prior chemotherapy in combination with a TKI (imatinib, N=3; dasatinib, N=5; ponatinib, N=5), with 3 patients having undergone allogeneic haematopoietic stem cell transplantation (allo-HSCT)...ConclusionAsciminib demonstrated promising clinical efficacy with satisfactory tolerance in this cohort of Ph+ leukaemias failing multiple lines of therapy. Further investigation of its therapeutic role in Ph+ ALL is warranted.
    Clinical
    |
    ABL1 (ABL proto-oncogene 1)
    |
    ABL1 T315I • ABL1 E255K
    |
    dasatinib • imatinib • Iclusig (ponatinib) • Bosulif (bosutinib) • Scemblix (asciminib)
    5ms
    Propensity Score Matching Comparing Asciminib Versus Ponatinib in Chronic Myeloid Leukemia Patients Who Failed Prior Tyrosine Kinase Inhibitor Therapy (ASH 2023)
    Background ASCEMBL trial has demonstrated superior efficacy of Asciminib (ASC) over Bosutinib in terms of molecular response, and event-free survival. These findings contribute valuable insights to the understanding of ASC and PON treatments in pts with specific disease characteristics and may have implications for personalized therapy decisions in the absence of clinical trials comparing these drugs. Our aim is to expand our PSM cohort.
    Clinical
    |
    ABL1 (ABL proto-oncogene 1)
    |
    ABL1 T315I
    |
    Iclusig (ponatinib) • Bosulif (bosutinib) • Scemblix (asciminib)
    5ms
    Outcome of Patients with Chronic Myeloid Leukemia in Chronic Phase Showing Clinical Resistance to Frontline Treatment with Second Generation Tyrosine Kinase Inhibitors. an Italian Prospective Study from the CML Campus (ASH 2023)
    Eighteen patients (in which no mutations were found) switched to third-line treatment after a median time of 11 months (0-45) (ponatinib, 8 pts; nilotinib, 1 pt; dasatinib, 3 pts; imatinib, 3 pts; bosutinib, 1 pts; asciminib, 2 pts). Our findings, collected from the prospective cohort of the CML Italian observational registry, show that CP-CML patients failing frontline 2G-TKI therapy, despite a complex management, may have still an acceptable prognosis and survival due to the availability of both multiple TKI options and SCT.
    Clinical
    |
    ABL1 (ABL proto-oncogene 1)
    |
    dasatinib • imatinib • Iclusig (ponatinib) • Tasigna (nilotinib) • Bosulif (bosutinib) • Scemblix (asciminib)
    5ms
    Incidence, Interpretation and Management of Liver Function Abnormalities in Patients with Chronic Myeloid Leukemia (CML) Treated with Tyrosine Kinase Inhibitors (TKI) (ASH 2023)
    229 females and 238 males (median age at diagnosis 47 yrs (range 11-90) had 955 separate TKI episodes: imatinib 406, dasatinib 222, nilotinib 189, bosutinib 87, ponatinib 28 and asciminib 23. With the exception of asciminib the previous association of TKI, homozygous Gilbert and hyperbilirubinemia was confirmed. Grade 1 transaminitis is common on all TKIs, with higher grades of severity most frequent on bosutinib. Patients experiencing abnormal transaminases on 1 st line TKI are likely to have similar problems on 2 nd and 3 rd line agents, with a trend to higher incidence/severity on nilotinib compared to dasatinib.
    Clinical
    |
    UGT1A1 (UDP glucuronosyltransferase family 1 member A1)
    |
    UGT1A1*1*1
    |
    dasatinib • imatinib • Iclusig (ponatinib) • Tasigna (nilotinib) • Bosulif (bosutinib) • Scemblix (asciminib)
    5ms
    Flumatinib for the Treatment of Adult Patients with Resistant or Intolerant Chronic-Phase Chronic Myeloid Leukemia: Results from Real-World Data (ASH 2023)
    Prior therapies included imatinib, dasatinib, nilotinib, olverembatinib, radotinib and ponatinib. Of the 58 patients, only Grade 1 AEs were reported, including diarrhea, rash and eye edema. Conclusion Flumatinib has good efficacy and safety in the treatment of adult patients with resistant or intolerant Chronic-Phase Chronic Myeloid Leukemia, it will be a good choice for second-line or above treatment for CML-CP In clinical practice.
    Clinical • Real-world evidence • Real-world
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    ABL1 (ABL proto-oncogene 1) • BCR (BCR Activator Of RhoGEF And GTPase)
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    dasatinib • imatinib • Iclusig (ponatinib) • Tasigna (nilotinib) • Nailike (olverembatinib) • Hansoh Xinfu (flumatinib) • Supect (radotinib)
    5ms
    Treatment-Free Remission in Ponatinib-Treated CML Patients: The Italy-Tfr Experience (ASH 2023)
    First-line therapy was available for 16 pts and was imatinib for 11 pts, nilotinib for 2 pts, dasatinib for 3 pts. Our data confirmed the efficacy of ponatinib in second or later lines of treatment. All pts, including those treated for resistance, achieved optimal responses at 3 mos. We also showed that TFR may be feasible for some pts treated in second or subsequent lines, not only for intolerance.
    Clinical
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    ABL1 (ABL proto-oncogene 1)
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    ABL1 T315I • ABL1 F359V • ABL1 Y253H
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    dasatinib • imatinib • Iclusig (ponatinib) • Tasigna (nilotinib)
    5ms
    In Vitro Evidence of Synergistically Enhanced Efficacy of Axitinib When Combined with Asciminib in T315I Mutated Chronic Myeloid Leukemia (ASH 2023)
    T315I mutation in ABL KD confers broad-spectrum resistance to all 1st- and 2nd-generation ABPIs including Imatinib (IMA), Dasatinib (DAS), Nilotinib (NIL) and Bosutinib (BOS). This result suggests synergistically enhanced inhibitory activity of dual blockade using AXI combined with ASC specifically for T315I mutant CML. This approach will be promising against CML cells carrying compound mutation with T315I mutation, which is highly resistant even to Ponatinib or Asciminib.
    Preclinical
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    ABL1 (ABL proto-oncogene 1)
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    ABL1 T315I
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    dasatinib • imatinib • Iclusig (ponatinib) • Tasigna (nilotinib) • Bosulif (bosutinib) • Inlyta (axitinib) • Scemblix (asciminib)
    5ms
    Minimal Residual Disease-Negative Complete Remission at the End of Induction Is a Prognostic Indicator of Long-Term Survival in Adult Patients with Ph+ Acute Lymphoblastic Leukemia Receiving First-Line Therapy (ASH 2023)
    Nine studies (n=704) were included in the aggregate study-level analysis; 3 of the 9 studies (Phase II AP24534-11-001 [Jabbour et al... These analyses indicate that a deeper molecular response at EOI results in better long-term EFS and OS; MRD-negative CR has a greater prognostic value than CR and is strongly associated with long-term EFS and OS in patients with Ph+ ALL.
    Clinical • Minimal residual disease
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    ABL1 (ABL proto-oncogene 1)
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    Iclusig (ponatinib)