- |||||||||| Iclusig (ponatinib) / Takeda, Otsuka, Blincyto (blinatumomab) / Astellas, Amgen, Besponsa (inotuzumab ozogamicin) / Pfizer, UCB
Review, Journal: Advances in the treatment of adults with newly diagnosed B-cell acute lymphoblastic leukemia: the role of frontline immunotherapy-based regimens. (Pubmed Central) - Jun 8, 2024
Blinatumomab and inotuzumab ozogamicin (INO) are both active in relapsed/refractory B-cell acute lymphoblastic leukemia (ALL) and improve outcomes compared with conventional chemotherapy in this setting...This review discusses novel approaches to integrating INO and/or blinatumomab into frontline ALL regimens, including the potential role of chemotherapy-free regimens in some subgroups. The role of MRD monitoring is also discussed, including how this can inform decisions for consolidative allogeneic HSCT or investigational approaches with CD19 CAR T-cells.
- |||||||||| Journal: Cancer Therapies and Cardiomyocyte Viability: Which Drugs are Directly Cardiotoxic? (Pubmed Central) - Jun 1, 2024
Some of those, have not been associated with clinical cardiotoxicity, while others, known to be cardiotoxic do not appear to mediate it via direct effects on cardiomyocytes. More detailed investigations of the effects of cancer therapies on various cardiovascular cells should be performed to comprehensively determine the mechanisms of cardiotoxicity.
- |||||||||| Iclusig (ponatinib) / Takeda, Otsuka, Blincyto (blinatumomab) / Astellas, Amgen, Besponsa (inotuzumab ozogamicin) / Pfizer, UCB
Review, Journal: SOHO State of the Art Updates and Next Questions | Next Questions: Acute Lymphoblastic Leukemia. (Pubmed Central) - May 30, 2024
In younger patients with Philadelphia chromosome (Ph)-negative ALL, treatment with Hyper-CVAD and blinatumomab +/- inotuzumab has improved the 3-year overall survival (OS) to above 85%...In Ph+ ALL, the chemotherapy-free combinations of blinatumomab and ponatinib (or dasatinib) have become a new standard of care resulting in 3-year OS of 85% to 90%. Because the methotrexate-cytarabine courses were omitted in the nonchemotherapy regimens, central nervous system (CNS) relapses were noted, particularly in patients with a WBC count > 70
- |||||||||| Iclusig (ponatinib) / Takeda, Otsuka
Review, Journal: Addendum to the German Consensus Recommendations on Ponatinib in the Treatment of Chronic Myeloid Leukemia. (Pubmed Central) - May 28, 2024
Because the methotrexate-cytarabine courses were omitted in the nonchemotherapy regimens, central nervous system (CNS) relapses were noted, particularly in patients with a WBC count > 70 The OPTIC data confirm the high efficacy of ponatinib in patients with CP-CML and provide the basis for individualized dose adjustment during the course of treatment.
- |||||||||| miransertib (MK-7075) / Merck (MSD), Ibrance (palbociclib) / Pfizer, Nerlynx (neratinib) / Puma
Journal, Combination therapy: Synergistic Effects of Neratinib in Combination With Palbociclib or Miransertib in Brain Cancer Cells. (Pubmed Central) - May 16, 2024
Notably, we found that treatment with neratinib in combination with palbociclib (CDK4/6 inhibitor), or miransertib (AKT1/2/3 inhibitor) resulted in synergistic growth inhibition of all HBCCLs. Our results support that repurposing drugs like neratinib in combination with the palbociclib or miransertib may be of therapeutic potential in brain cancer and warrants further investigations.
- |||||||||| Iclusig (ponatinib) / Takeda, Otsuka
Review, Journal: Ponatinib-review of historical development, current status, and future research. (Pubmed Central) - May 10, 2024
Ponatinib-based therapy also resulted in significantly better outcomes in frontline Ph-positive ALL compared with prior TKIs and is becoming a new standard of care in this setting. As the clinical development of third-generation TKIs and their rational combinations progresses, we envision further transformative changes in the treatment of CML and Ph-positive ALL.
- |||||||||| Iclusig (ponatinib) / Takeda, Otsuka, Incyte
Journal: Concurrent inhibition of IR, ITGB1, and CD36 perturbated the interconnected network of energy metabolism and epithelial-to-mesenchymal transition in breast cancer cells. (Pubmed Central) - May 5, 2024
Moreover, the reduction in fatty acid uptake, lipid droplet accumulation, cancer stemness, and migration properties were also observed. Thus, targeting IR, ITGB1, and CD36 in the interconnected network with the combination of Pimozide and Ponatinib represents a promising therapeutic approach for breast cancer.
- |||||||||| imatinib / Generic mfg.
Incident primary HIV infection during chronic treatment with imatinib: effect on reservoir dynamics (Poster board: 018) - May 2, 2024 - Abstract #AIDS2024AIDS_1038;
The embargo on all abstracts, including oral abstract, poster exhibition, e-poster and late breakers, will lift on Tuesday, 23 July 2024, at 10:00 am Central European Summer Time (CEST). If an abstract is part of an official AIDS 2024 press conference that occurs before that time, the embargo on that abstract lifts at the start of the official press conference.
- |||||||||| Iclusig (ponatinib) / Takeda, Otsuka, Incyte, Blincyto (blinatumomab) / Astellas, Amgen
Review, Journal: SOHO State of the Art Updates and Next Questions: Update on the Approach to Philadelphia Chromosome-Positive Acute Lymphoblastic Leukemia. (Pubmed Central) - Apr 25, 2024
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.
- |||||||||| Iclusig (ponatinib) / Takeda, Otsuka
Real-world analysis of HyperCVAD + TKI for untreated Ph+ ALL. () - Apr 24, 2024 - Abstract #ASCO2024ASCO_5663;
While 2-yr OS and EFS are similar in our cohort to published data, a surprisingly large number of patients experienced molecular relapse, which was not reported in the original trial. While our sample size was small, there was no significant difference in CR or transplant status for patients treated with Hyper CVAD + ponatinib versus alternate TKI.
- |||||||||| Scemblix (asciminib) / Novartis
Cardiovascular complications associated with asciminib use: A retrospective analysis. (Hall A; Poster Bd #: 122) - Apr 24, 2024 - Abstract #ASCO2024ASCO_1200;
This study emphasizes the importance of using patient records and medical research to obtain complete information. Patients with underlying risk factors for the development of cardiovascular diseases should be thoroughly evaluated before drug initiation.
- |||||||||| Iclusig (ponatinib) / Takeda, Otsuka
In-depth analysis of responders in the phase 3 PhALLCON trial of ponatinib vs imatinib in newly diagnosed Ph+ ALL. (Hall A; Poster Bd #: 92) - Apr 24, 2024 - Abstract #ASCO2024ASCO_1170;
P3
Patients with underlying risk factors for the development of cardiovascular diseases should be thoroughly evaluated before drug initiation. Ponatinib was superior to imatinib in combination with reduced-intensity chemotherapy for frontline treatment of Ph+ ALL, with higher rates of MRD-neg at any time, substantially longer PFS across age and BCR::ABL1 variant subgroups, and a safety profile comparable to imatinib.
- |||||||||| Scemblix (asciminib) / Novartis
Journal: Asciminib Maintains Antibody-Dependent Cellular Cytotoxicity against Leukemic Blasts. (Pubmed Central) - Apr 13, 2024
P1/2, P2
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.
- |||||||||| Taltorvic (ridaforolimus) / Takeda, Merck (MSD)
Review, Journal: Clinical research progress of ridaforolimus (AP23573, MK8668) over the past decade: a systemic review. (Pubmed Central) - Apr 8, 2024
Rapamycin, an established mTOR inhibitor in clinical practice, is widely recognized for its therapeutic efficacy...These trials employed diverse drug combinations, incorporating agents such as ponatinib, bicalutamide, dalotuzumab, MK-2206, MK-0752, and taxanes...Our review encompassed analyses of signaling pathways, ridaforolimus as a single therapeutic agent, its compatibility in combination with other drugs, and an assessment of adverse events (AEs). We conclude by recommending further research to advance our understanding of ridaforolimus's clinical applications.
- |||||||||| Iclusig (ponatinib) / Takeda, Otsuka, Incyte
Journal: Potential protein kinase inhibitors that target G-quadruplex DNA structures in the human telomeric regions. (Pubmed Central) - Mar 21, 2024
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.
- |||||||||| Bosulif (bosutinib) / Pfizer, Iclusig (ponatinib) / Takeda, Otsuka, Incyte, Tasigna (nilotinib) / Novartis, Inhibikase
Retrospective data, Journal, Real-world evidence, Real-world: Comorbidities and outcomes of patients with chronic myeloid leukemia treated with tyrosine kinase inhibitors: a real-world, nationwide, retrospective study from Hungary. (Pubmed Central) - Mar 10, 2024
We found slightly lower OS rates compared to other European countries, however, there was a statistically significant improvement in 4-year OS during the study period. The management of CML was in line with international guidelines and recommendations.
- |||||||||| Ba/F3-BCR-ABL engineering cell line panel, a useful platform for novel drug discovery (Section 10) - Mar 5, 2024 - Abstract #AACR2024AACR_9764;
Each cell was validated by cell sequencing and cell efficacy verification using approved BCR-ABL inhibitors. The Ba/F3-BCR-ABL engineering cell line panel can be useful for developing and evaluating next-generation BCR-ABL inhibitors and exploring newly acquired resistance mutations in BCR-ABL.
- |||||||||| Genomic mechanisms of RET inhibitor resistance in RET-fusion positive NSCLC (Section 23) - Mar 5, 2024 - Abstract #AACR2024AACR_8077;
Collectively, we show that individual RET fusion variants have distinct drug sensitivity profiles and that secondary resistance mutations are non-overlapping between RETi. The comprehensive characterization of RET-dependent mechanisms of resistance to RETi may provide therapeutic guidance for treating RET-fusion driven NSCLC and provide structural insights that can guide the development of new therapeutic regimens.
- |||||||||| Iclusig (ponatinib) / Takeda, Otsuka, Incyte
Role of MAPK11 in the protective mechanisms against toxicity of tyrosine kinase inhibitors (Section 39) - Mar 5, 2024 - Abstract #AACR2024AACR_7864;
The comprehensive characterization of RET-dependent mechanisms of resistance to RETi may provide therapeutic guidance for treating RET-fusion driven NSCLC and provide structural insights that can guide the development of new therapeutic regimens. Our study suggests that the inhibition of MAPK11 is a potential druggable therapeutic target with dual action of anti-cancer effect for the mutant form of CML, as well as a substantial protective effect against the cardiac toxicity associated with the TKI ponatinib that could bring insights in the development of safer oncological drugs.
- |||||||||| Iclusig (ponatinib) / Takeda, Otsuka, Incyte
Macrophage instead of leukemia cell expressed PD-L1 drives T cell exhaustion and immune evasion of BCRABL1 chronic myeloid leukemia (Section 7) - Mar 5, 2024 - Abstract #AACR2024AACR_3256;
For translational purpose, mice transplanted with the primary CML leukemia cells were treated with chemotherapy drugs ponatinib alone or in combination with the anti-PD1 antibody...Most importantly, the disease relapse occurred at a slower rate after treatment discontinuation, suggesting the value of combinational therapy in achieving treatment free remission. In summary, our study not only revealed the dynamic changes of immune microenvironment in the BCRABL1 CML mouse model, but also revealed the different mechanisms underlying immune evasion of BCR-ABL1 CML leukemia cells, which sheds light on a combinational treatment for achieving the treatment free remission of CML.
- |||||||||| Iclusig (ponatinib) / Takeda, Otsuka, Incyte
Journal: Ponatinib-Induced Cardiomyocyte Toxicity: Dark Side of the Integrated Stress Response. (Pubmed Central) - Mar 4, 2024
In summary, our study not only revealed the dynamic changes of immune microenvironment in the BCRABL1 CML mouse model, but also revealed the different mechanisms underlying immune evasion of BCR-ABL1 CML leukemia cells, which sheds light on a combinational treatment for achieving the treatment free remission of CML. No abstract available
- |||||||||| Review, Journal: The VEGFs/VEGFRs system in Alzheimer's and Parkinson's diseases: pathophysiological roles and therapeutic implications. (Pubmed Central) - Mar 4, 2024
Specific VEGFRs targeting, aimed at selective VEGFR-1 inhibition, while preserving VEGFR-2 signal transduction, appears as a promising strategy to hit the molecular mechanisms underlying AD pathology. Moreover, therapeutic VEGF-based approaches can be proposed for PD treatment, with the aim of fine-tuning its brain levels to amplify its neurotrophic/neuroprotective effects while limiting an excessive impact on vascular permeability.
- |||||||||| Iclusig (ponatinib) / Takeda, Otsuka, Incyte
Journal: Integrated Stress Response Potentiates Ponatinib-Induced Cardiotoxicity. (Pubmed Central) - Mar 4, 2024
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.
- |||||||||| Iclusig (ponatinib) / Takeda, Otsuka
Enrollment closed, Trial completion date: A Study of Ponatinib With Chemotherapy in Children, Teenagers, and Adults With Philadelphia Chromosome-Positive Acute Lymphoblastic Leukemia (clinicaltrials.gov) - Mar 3, 2024
P1/2, N=68, Active, not recruiting,
Active, not recruiting --> Terminated; Low accrual Trial completion date: Aug 2027 --> Jan 2027 | Recruiting --> Active, not recruiting
- |||||||||| Iclusig (ponatinib) / Takeda, Otsuka, Blincyto (blinatumomab) / Astellas, Amgen
Trial completion date, Trial primary completion date: 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) - Mar 2, 2024
P2, N=90, Recruiting,
Trial completion date: Aug 2027 --> Jan 2027 | Recruiting --> Active, not recruiting Trial completion date: Nov 2024 --> Nov 2025 | Trial primary completion date: Nov 2024 --> Nov 2025
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