- |||||||||| Iclusig (ponatinib) / Takeda, Otsuka
Trial completion date, Trial initiation date, Trial primary completion date, Minimal residual disease: Ponatinib in Adult Ph+ ALL Patients With MRD Positivity or Hematological Relapse (clinicaltrials.gov) - Jan 4, 2021 P2, N=67, Not yet recruiting, Study demographics and patient destinations Trial completion date: Jul 2024 --> Nov 2024 | Initiation date: Oct 2020 --> Feb 2021 | Trial primary completion date: Jul 2022 --> Nov 2022
- |||||||||| Iclusig (ponatinib) / Takeda, Otsuka, Incyte
Journal, PARP Biomarker, IO biomarker: Involvement of MCL1, c-myc, and cyclin D2 protein degradation in ponatinib-induced cytotoxicity against T315I(+) Ph+leukemia cells. (Pubmed Central) - Dec 30, 2020 T315I mutation found in chronic myelogenous leukemia (CML) and Ph + ALL patients is the most serious one among resistance against BCR/ABL kinase inhibitors including imatinib and is only responsive to ponatinib (PNT)...PNT induced apoptosis (increased sub G1 cells, and cleaved caspase3 and PARP), and suppressed protein expression of MCL1, cyclin D2 and c-myc, which were reversed by a proteasome inhibitor, MG132, suggesting enhanced proteasomal degradation by PNT...Moreover, GSK3 inhibitor (SB216763) reduced PNT-induced cytotoxicity and degradation of c-myc and MCL1. AZD5991 exhibited the synergistic action with PNT, anti-cancer drugs and venetoclax (BCL2 inhibitor), suggesting the utility of MCL1 inhibitor alone or in combination as a future clinical option for Ph + leukemia patients.
- |||||||||| Iclusig (ponatinib) / Takeda, Otsuka, Blincyto (blinatumomab) / Astellas, Amgen
New P2 trial, Combination therapy: EWALL-Ph-03: Study in Adult Ph-positive ALL (clinicaltrials.gov) - Dec 29, 2020 P2, N=180, Not yet recruiting,
- |||||||||| Iclusig (ponatinib) / Takeda, Otsuka, Incyte
Clinical, Journal: Experience with ponatinib in paediatric patients with leukaemia. (Pubmed Central) - Dec 18, 2020 Toxicities were similar to those reported in adults, with the exception of arterial thrombotic events, which were not observed. Ponatinib has a favourable safety profile in this paediatric cohort, but dose-finding studies are needed.
- |||||||||| asciminib (ABL001) / Novartis, Iclusig (ponatinib) / Takeda, Otsuka, Incyte
Clinical, Journal, Adverse events: A Global PROTAC Toolbox for Degrading BCR-ABL Overcomes Drug-Resistant Mutants and Adverse Effects. (Pubmed Central) - Dec 16, 2020 We provided a global PROTAC toolbox for degrading both wild type and T315I mutated BCR-ABL from each binding site. More importantly, these PROTACs showed better selectivity and less adverse effects than inhibitors, indicating that PROTACs had a great potential for overcoming clinical drug resistance and safety issues.
- |||||||||| asciminib (ABL001) / Novartis, Iclusig (ponatinib) / Takeda, Otsuka, Incyte, Tasigna (nilotinib) / Novartis, Inhibikase
[VIRTUAL] COVID-19 IN CHRONIC MYELOID LEUKEMIA PATIENTS - BRAZILIAN EXPERIENCE () - Nov 26, 2020 - Abstract #HEMO2020HEMO_887; Although the sample size is still small to make conclusions regarding COVID-19 behavior in CML patients, the most severe cases occurred in patients not in MMR. The continued register of the cases will increase our knowledge about this disease and how to manage these patients.
- |||||||||| Iclusig (ponatinib) / Takeda, Otsuka, Incyte
[VIRTUAL] LLA-B, PHILADELPHIA + RECURRENT AFTER BONE MARROW TRANSPLANTATION, WITH RESPONSE TO PONATINIBE: CASE REPORT () - Nov 26, 2020 - Abstract #HEMO2020HEMO_279; At the end of the first blinatumomab cycle, she presented negative DRM...He switched desatinib to ponatinib 30 mg / day, with prednisone and weekly doses of vincristine on 06/13/2020, without complications...The prognosis of patients with recurrent Ph + ALL after allogeneic BMT is reserved, and few therapeutic options are viable, including: donor lymphocyte infusion, conventional chemotherapy, immunotherapy (blinatomumab, inotuzumab ozogamycin), therapy with CAR-T cells, according to TMO allogeneic and exclusive supportive care, but the overall survival rates for this population at 3 years are less than 25%... Patient with ALL-B, Ph +, relapsed after allogeneic bone marrow BMT compatible, refractory to blinatomumab and conventional chemotherapy, which achieved a rapid response with the use of ponatinib associated with corticosteroids and vincristine, allowing for a second haploidentic BMT.
- |||||||||| Iclusig (ponatinib) / Takeda, Otsuka, Incyte
[VIRTUAL] REFLATORY CHRONIC MYELOID LEUKEMIA - PRESENCE OF MUTATION T315I AND RESPONSE TO PONATINIBE () - Nov 26, 2020 - Abstract #HEMO2020HEMO_211; The patient underwent cytoreductive therapy with Hydroxyurea for nine months, with subsequent initiation of 1st generation tyrosine kinase inhibitor (ITK) with Imatinib 400 mg / day in March 2017...We opted for the 2nd line of treatment with 2nd generation ITK with Nilotinib 800 mg / day in July 2017...Patient intervened in July / 2018 with progression to an accelerated phase, with 15% of myeloid blasts in a peripheral blood smear; cytoreductive therapy with Cytarabine 100 mg / m2...It was decided to conduct a T315I and F359V mutation research at the time, both present; in a new cytogenetic evaluation after four months of using Dasatinib, t (9; 22) was observed in 84% of the cells analyzed... In patients with CML refractory to 1st and 2nd generation ITK it is essential to study mutations in BCR-ABL, since Ponatinib shows excellent results, with hematological, cytogenetic and molecular responses.
- |||||||||| Iclusig (ponatinib) / Takeda, Otsuka, Incyte
Journal: Role of Elevated Thrombospondin-1 in Kainic Acid-Induced Status Epilepticus. (Pubmed Central) - Nov 22, 2020 Moreover, inhibiting Smad2/3 phosphorylation with ponatinib or SIS3 also significantly reduced seizure severity, alongside reducing GFAP/CS56 immunoreactivity. These results suggest that the TSP-1-regulated TGF-β1/pSmad2/3 pathway plays a key role in KA-induced SE and astrogliosis, and that inhibiting this pathway may be a potential anti-seizure strategy.
- |||||||||| Iclusig (ponatinib) / Takeda, Otsuka
Trial primary completion date: OPTIC-2L: A Study Comparing Ponatinib and Nilotinib in Participants With Chronic Myeloid Leukemia (clinicaltrials.gov) - Nov 20, 2020 P3, N=44, Active, not recruiting, These results suggest that the TSP-1-regulated TGF-β1/pSmad2/3 pathway plays a key role in KA-induced SE and astrogliosis, and that inhibiting this pathway may be a potential anti-seizure strategy. Trial primary completion date: Jan 2020 --> Nov 2020
- |||||||||| Bosulif (bosutinib) / Pfizer, Iclusig (ponatinib) / Takeda, Otsuka, Incyte, Tasigna (nilotinib) / Novartis, Inhibikase
Clinical, Journal: Contemporary treatment methods of adult patients with BCR/ABL1 positive chronic myeloid leukemia. (Pubmed Central) - Nov 12, 2020 Although, one third of patients does not respond well to first line imatinib and needs to change the treatment to second line tyrosine kinase inhibitors (TKI: bosutinib, dasatinib and nilotinib)...For patients who are resistant simultaneously to 2nd generation TKI and for patients with mutation T315I ponatinib - TKI of 3rd generation can be used effectively...Patient´s cooperation with medical team is crucial and inevitable in long time treatment process. The chance for TFR has become feasible for approximately 40-60 % CML patients in deep and durable molecular remission and represents a further important milestone in the management of CML patients.
- |||||||||| Iclusig (ponatinib) / Takeda, Otsuka, Incyte
[VIRTUAL] Next-Generation Sequencing in Non-BCR-ABLMechanisms Resistance in Patients with Chronic Myeloid Leukemia: Results of a Pilot Study () - Nov 5, 2020 - Abstract #ASH2020ASH_5192; In 2 patients with the simultaneous presence of mutations in theATRXandTET2genes, resistance to 2 TKIs was registered; CCyR without MMR was achieved only with ponatinib...This allowed us to suggest the prognostic and therapeutic value of mutations in theNF1,ATRXandSTAG2genes in CP CML patients with resistance to TKI therapy. Conclusion.The obtained results of a pilot study of NGS use for predictingBCR-ABL-independent resistance to TKI therapy in patients with CML can serve as a basis for further research aimed at developing prognostic models and choosing a treatment method for resistance to targeted therapy.
- |||||||||| azacitidine / Generic mfg.
[VIRTUAL] Myeloid Blast Crisis of Philadelphia Positive Chronic Myeloid Leukemia and Philadelphia Positive Acute Myeloid Leukemia Treated at the AP-HP in Paris: A Retrospective Analysis () - Nov 5, 2020 - Abstract #ASH2020ASH_5189; 11/64 pts (17%) started Azacytidine (1 pt in combination with Imatinib, 2 pts with Nilotinib, 6 pts with Dasatinib, 1 pt with Ponatinib and 1 pt with Venetoclax)...Already published experiences showed a generical dismal prognosis with median OS which doesn't exceed 1-2 years (16 months, Deau B, Leukemia Research 2011 ; 12 months, Palandri F, Haematologica 2008 ; 6.4 months, Fruehauf S, Cancer 2007) whereas in our real life cohort median OS was longer. For fit and potentially « transplantable » patients, combination with classic chemotherapy plus a TKI seems reasonable and associated with good outcomes in terms of OS and EFS.
- |||||||||| Bosulif (bosutinib) / Pfizer, Iclusig (ponatinib) / Takeda, Otsuka, Incyte, Tasigna (nilotinib) / Novartis, Inhibikase
[VIRTUAL] Cardiovascular Toxicities of Tyrosine Kinase Inhibitor in CML () - Nov 5, 2020 - Abstract #ASH2020ASH_5186; Out of the reported cases of AEs to TKIs approved for front line CML, nilotinib appears to have more CV AE compared to imatinib, dasatinib and bolutinib. Imatinib appears to have least CV AE out of the total AEs reported
- |||||||||| asciminib (ABL001) / Novartis
[VIRTUAL] Structural and Biochemical Studies Confirming the Mechanism of Action of Asciminib, an Agent Specifically Targeting the ABL Myristoyl Pocket (STAMP) () - Nov 5, 2020 - Abstract #ASH2020ASH_5179; Secondly, by not inhibiting kinases such as EGFR, KIT, CSF1R, PDGFR or the sSRC-family kinases that are associated with off-target activities of TKIs such as bosutinib, dasatinib, imatinib, nilotinib and ponatinib, asciminib is not expected to be associated with cross-intolerance. Thirdly, asciminib can bind to the ABL1 kinase domain together with ATP-competitive TKIs to form ternary complexes, such that appropriate drug combinations should greatly impede the emergence of drug resistant kinase mutations.
- |||||||||| Iclusig (ponatinib) / Takeda, Otsuka, Incyte, Tasigna (nilotinib) / Novartis, Inhibikase
[VIRTUAL] The Pivotal Role of Nicotinamide Phosphoribosyl Transferase in Chronic Myeloid Leukemia Cells Under Hypoxic Condition () - Nov 5, 2020 - Abstract #ASH2020ASH_5178; Materials and In this study, we established ABL TKI resistantin vitrocell line models (K562 imatinib-R, K562 nilotinib-R, K562 ponatinib-R and Ba/F3 T315I) and used Ph-positive leukemia cell lines. The results of our study indicate that the ABL TKI and CHS828 may be a powerful strategy against Ph-positive cells including ABL TKI resistant cells and provide the promising clinical relevance as a candidate drug for treatment of CML stem cells of the bone marrow microenvironment under hypoxic condition.
- |||||||||| [VIRTUAL] Developing Novel Targeted Therapies Using the High-Risk Vq Myeloma Model (Channel 11 (Virtual Meeting)) - Nov 5, 2020 - Abstract #ASH2020ASH_4459;
Our study demonstrates the utility of the VQ model for identifying new treatments for hrrMM and testing their efficacy in vivo. As part of our ongoing drug repurposing experiments, we have expanded our screening to a panel of 2,580 FDA-approved drugs, including but not limited to anti-cancer and anti-inflammatory drugs.
- |||||||||| Bosulif (bosutinib) / Pfizer, Iclusig (ponatinib) / Takeda, Otsuka, Incyte, Tasigna (nilotinib) / Novartis, Inhibikase
[VIRTUAL] COVID-19 in Patients (pts) with Chronic Myeloid Leukemia (CML): Results from the International CML Foundation (iCMLf) CML and COVID-19 (CANDID) Study (Channel 4 (Virtual Meeting)) - Nov 5, 2020 - Abstract #ASH2020ASH_4439; Five (5%) pts were taking bosutinib, 12 (11%) dasatinib, 39 (36%) imatinib, 17 (16%), nilotinib, 2 (2%) ponatinib, 1 (1%) HQP1315 and 1 pt (1%) was treated with an unknown TKI...Imatinib may represent a confounder as opposed to a true adverse prognostic predictor given the strong link between imatinib treatment and advanced age. Further case reports and longer follow up are needed to better ascertain independent risk factors, the impact of COVID-19, and the possible role that TKI type may play in this population.
- |||||||||| Bosulif (bosutinib) / Pfizer, Iclusig (ponatinib) / Takeda, Otsuka, Incyte, Tasigna (nilotinib) / Novartis, Inhibikase
[VIRTUAL] Contemporary Practice Patterns of Tyrosine Kinase Inhibitor Use Among Older Patients with Chronic Myeloid Leukemia in the United States (Poster Hall (Virtual Meeting)) - Nov 5, 2020 - Abstract #ASH2020ASH_4241; We identified 5 available TKIs (imbatinib, bosutinib, dasatinib, nilotinib, and ponatinib) for the treatment of CML from diagnosis to the end of follow-up...A total of 241 (29.1%) TKI users also received hydroxyurea after diagnosis...One-third of 1L TKI users switched to another TKI LOT with one-quarter of pts switching from 1L imatinib eventually returning to imatinib, suggesting that the toxicity of imatinib is likely tolerable among those older CML pts. This work was supported by the Frederick A. DeLuca Foundation.
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