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https://www.readbyqxmd.com/read/29032022/outcomes-of-newly-diagnosed-chronic-phase-chronic-myeloid-leukemia-following-an-elective-switch-from-second-generation-tyrosine-kinase-inhibitor-to-imatinib
#1
Vamsi K Kota, Jee Hyun Kong, Martha Arellano, Fuad El Rassi, Manila Gaddh, Leonard T Heffner, Elliott F Winton, Anand P Jillella, Morgan L McLemore, H Jean Khoury
The second-generation tyrosine kinase inhibitors (TKIs) (2G-TKIs) dasatinib (DAS) and nilotinib (NIL) yield faster responses in newly diagnosed chronic phase (CP) chronic myeloid leukemia (CML) as compared with imatinib (IM); however, long-term safety of these agents is a growing concern. We identified 20 patients with CP-CML diagnosed between August 2013 and October 2016 who initiated 2G-TKIs and were then switched after optimal response at 3 months to IM. Second-generation TKIs initiated were DAS (n = 15), NIL (n = 3), or both sequentially due to intolerance (n = 1)...
September 19, 2017: Clinical Lymphoma, Myeloma & Leukemia
https://www.readbyqxmd.com/read/29027261/prognostic-significance-of-additional-chromosomal-abnormalities-at-the-time-of-diagnosis-in-patients-with-chronic-myeloid-leukemia-treated-with-frontline-tyrosine-kinase-inhibitors
#2
Ahmad Alhuraiji, Hagop Kantarjian, Prajwal Boddu, Farhad Ravandi, Gautam Borthakur, Courtney DiNardo, Naval Daver, Tapan Kadia, Naveen Pemmaraju, Sherry Pierce, Guillermo Garcia-Manero, William Wierda, Srdan Verstovsek, Elias Jabbour, Jorge Cortes
Additional cytogenetic abnormalities (ACA) are considered a high risk feature in chronic myeloid leukemia (CML). However, its prognostic significance at the time of diagnosis in the setting of new tyrosine kinase inhibitors (TKIs) is less well understood. Patients with CML in CP with or without ACA at diagnosis treated with frontline TKIs in prospective clinical trials were analyzed for outcomes. Among 603 patients treated, 29 (5%) had ACA. Patients with ACA included 2 of 72 (2.8%) treated with imatinib 400 mg, 9 of 207 (4...
October 13, 2017: American Journal of Hematology
https://www.readbyqxmd.com/read/28990873/third-line-treatment-with-second-generation-tyrosine-kinase-inhibitors-dasatinib-or-nilotinib-in-patients-with-chronic-myeloid-leukemia-after-two-prior-tkis-real-life-data-on-a-single-center-experience-along-with-the-review-of-the-literature
#3
Seniz Ongoren, Ahmet Emre Eskazan, Veysel Suzan, Sercan Savci, Isil Erdogan Ozunal, Selin Berk, Fevzi Fırat Yalniz, Tugrul Elverdi, Ayse Salihoglu, Yucel Erbilgin, Sibel Aylin Iseri, Muhlis Cem Ar, Zafer Baslar, Yildiz Aydin, Nukhet Tuzuner, Ugur Ozbek, Teoman Soysal
OBJECTIVES: Newer tyrosine kinase inhibitors (TKIs) (bosutinib, ponatinib) and allogeneic hematopoietic stem cell transplantation (allo-HSCT) can be utilized as a salvage therapy in patients with chronic myeloid leukemia (CML) who failed two lines (imatinib → nilotinib or imatinib → dasatinib) of TKI therapy. However, these TKIs are not available in many countries and not all patients can undergo allo-HSCT. METHODS: In this study, CML patients who received dasatinib or nilotinib as a third-line treatment were retrospectively evaluated...
October 9, 2017: Hematology (Amsterdam, Netherlands)
https://www.readbyqxmd.com/read/28983061/bcr-abl1-compound-mutants-display-differential-and-dose-dependent-responses-to-ponatinib
#4
Konstantin Byrgazov, Chantal Blanche Lucini, Peter Valent, Oliver Hantschel, Thomas Lion
No abstract text is available yet for this article.
October 5, 2017: Haematologica
https://www.readbyqxmd.com/read/28978841/treatment-of-relapsed-or-refractory-acute-lymphoblastic-leukemia
#5
Kiyotoshi Imai
Most patients with adult acute lymphoblastic leukemia (ALL) undergo relapse, despite the achievement of complete remission with chemotherapy. Among patients with relapsed or refractory ALL, remission rates are 18-44% with the use of standard salvage chemotherapy, but the duration of remission is short. A major goal in this population is to induce remission with a sufficient duration to prepare for stem cell transplantation. The poor outcomes and lack of durable responses seen with conventional chemotherapy have led to the development of several novel agents, including clofarabine and nelarabine...
2017: [Rinshō Ketsueki] the Japanese Journal of Clinical Hematology
https://www.readbyqxmd.com/read/28978814/erratum-pharmacological-characteristics-and-clinical-outcomes-of-ponatinib-iclusig-%C3%A2-a-third-generation-tyrosine-kinase-inhibitor
#6
(no author information available yet)
No abstract text is available yet for this article.
2017: Nihon Yakurigaku Zasshi. Folia Pharmacologica Japonica
https://www.readbyqxmd.com/read/28972430/life-after-ponatinib-failure-outcomes-of-chronic-and-accelerated-phase-cml-patients-who-discontinued-ponatinib-in-the-salvage-setting
#7
Prajwal Boddu, Abdul Rashid Shah, Gautam Borthakur, Srdan Verstovsek, Guillermo Garcia-Manero, Naval Daver, Tapan Kadia, Farhad Ravandi, Nitin Jain, Ahmad Alhuraiji, Jan Burger, Steven Kornblau, Sherry Pierce, Sara Dellasala, Elias Jabbour, Hagop Kantarjian, Jorge Cortes
Ponatinib is a pan-tyrosine kinase inhibitor (TKI) with efficacy in multirefractory CML patients who have failed other TKIs. Despite excellent response rates, resistance or intolerance may develop. We conducted a retrospective review of the outcome of patients with chronic (CP) and accelerated (AP) phase CML refractory to prior TKI who discontinued ponatinib for resistance or intolerance. Nineteen CP patients, discontinued due to resistance (n = 13), toxicity (n = 5) and to pursue stem cell transplantation (n = 1)...
October 3, 2017: Leukemia & Lymphoma
https://www.readbyqxmd.com/read/28969556/ponatinib-a-review-of-efficacy-and-safety
#8
Fulvio Massaro, Matteo Molica, Massimo Breccia
Ponatinib is a third generation kinase inhibitor designed to overcome the gatekeeper T315I mutation. In different trials this drug showed inhibitory activity against native BCR-ABL1 kinase and several ABL1 mutations. For this reason, ponatinib is currently indicated for the treatment of chronic myeloid leukaemia (CML) in every phase of disease resistant and/or intolerant to dasatinib and nilotinib and for whom imatinib is not indicated anymore or for patients with T315I mutation. The drug is also indicated for Ph+ acute lymphoblastic leukaemia (ALL)...
October 2, 2017: Current Cancer Drug Targets
https://www.readbyqxmd.com/read/28942039/comparative-effect-of-imatinib-and-ponatinib-on-autophagy-and-mirnome-in-chronic-myeloid-leukemia
#9
Cagla Kayabasi, Tugce Balci Okcanoglu, Besra Ozmen Yelken, Aycan Asik, Sunde Yilmaz Susluer, Cigir Biray Avci, Guray Saydam, Cumhur Gunduz
BCR-ABL tyrosine kinase inhibitors (TKIs) are selective therapies for the patients with Chronic Myeloid Leukemia (CML). Imatinib and ponatinib have remarkable long-term efficacy on a major molecular response. Although TKI related induction of cytotoxicity and apoptosis have been clearly investigated in molecular levels, their comparative effect on autophagy and miRNome are largely unknown. This study aimed to investigate the involvement of alterations of miRNA expressions in CML progression, and how imatinib and ponatinib affect this process, by comparing CML, imatinib-resistant CML and leukemia stem cells (LSC)...
December 30, 2017: Gene
https://www.readbyqxmd.com/read/28927784/safety-and-efficacy-of-blinatumomab-in-combination-with-a-tyrosine-kinase-inhibitor-for-the-treatment-of-relapsed-philadelphia-chromosome-positive-leukemia
#10
Rita Assi, Hagop Kantarjian, Nicholas J Short, Naval Daver, Koichi Takahashi, Guillermo Garcia-Manero, Courtney DiNardo, Jan Burger, Jorge Cortes, Nitin Jain, William Wierda, Salim Chamoun, Marina Konopleva, Elias Jabbour
OBJECTIVE: The treatment of Philadelphia chromosome-positive (Ph+) acute lymphoblastic leukemia has been revolutionized with the introduction of tyrosine kinase inhibitors (TKIs) and the combination of these agents with chemotherapy. Blinatumomab is a bispecific anti-CD3/CD19 monoclonal antibody with clinical activity as single-agent in the relapsed setting and independent of BCR-ABL1 mutational status, including T315I. The combination of blinatumomab with a TKI may further improve outcomes for this high-risk population, including higher eradication of minimal residual disease and minimize the use of chemotherapy...
August 18, 2017: Clinical Lymphoma, Myeloma & Leukemia
https://www.readbyqxmd.com/read/28918995/cutaneous-adverse-events-of-targeted-therapies-for-hematolymphoid-malignancies
#11
REVIEW
Julia D Ransohoff, Bernice Y Kwong
The identification of oncogenic drivers of liquid tumors has led to the rapid development of targeted agents with distinct cutaneous adverse event (AE) profiles. The diagnosis and management of these skin toxicities has motivated a novel partnership between dermatologists and oncologists in developing supportive oncodermatology clinics. In this article we review the current state of knowledge of clinical presentation, mechanisms, and management of the most common and significant cutaneous AEs observed during treatment with targeted therapies for hematologic and lymphoid malignancies...
July 14, 2017: Clinical Lymphoma, Myeloma & Leukemia
https://www.readbyqxmd.com/read/28890835/ponatinib-as-a-valid-alternative-strategy-in-patients-with-blast-crisis-chronic-myeloid-leukemia-not-eligible-for-allogeneic-stem-cells-transplantation-and-or-conventional-chemotherapy-report-of-a-case
#12
Cristina Bucelli, Daniele Cattaneo, Valeria Ferla, Manuela Zappa, Caterina de Benedittis, Simona Soverini, Alessandra Iurlo
Currently, imatinib and dasatinib are the only tyrosine-kinase inhibitors approved in the US and Europe for the treatment of blast crisis of chronic myeloid leukemia (BC-CML) at diagnosis, while ponatinib is the only inhibitor used in patients bearing T315I mutation. Here we report the case of a 61-year-old man diagnosed with B-cell lymphoid BC-CML, initially treated with imatinib 800 mg day and then with dasatinib 140 mg day because of intolerance. A complete cytogenetic response (CCyR) was achieved at three months; however, three months later a relapse was observed, and the T315I mutation was detected...
2017: Case Reports in Hematology
https://www.readbyqxmd.com/read/28882992/novel-pathways-of-ponatinib-disposition-catalyzed-by-cyp1a1-involving-generation-of-potentially-toxic-metabolites
#13
De Lin, Rumen Kostov, Jeffrey T-J Huang, Colin J Henderson, C Roland Wolf
Ponatinib, a pan-BCR-ABL tyrosine kinase inhibitor for the treatment of chronic myeloid leukemia (CML), causes severe side effects including vascular occlusions, pancreatitis, and liver toxicity, although the underlying mechanisms remain unclear. Modifications of critical proteins through reactive metabolites are thought to be responsible for a number of adverse drug reactions. In vitro metabolite screening of ponatinib with human liver microsomes and glutathione revealed unambiguous signals of ponatinib-glutathione (P-GSH) adducts...
October 2017: Journal of Pharmacology and Experimental Therapeutics
https://www.readbyqxmd.com/read/28881484/primary-cells-in-bcr-fgfr1-positive-8p11-myeloproliferative-syndrome-are-sensitive-to-dovitinib-ponatinib-and-dasatinib
#14
Niklas Landberg, Arta Dreimane, Marianne Rissler, Rolf Billström, Helena Ågerstam
OBJECTIVES: Translocations involving the fibroblast growth factor receptor 1 (FGFR1) gene are associated with the 8p11 myeloproliferative syndrome (EMS), a rare neoplasm that following a usually short chronic phase progresses into acute myeloid or lymphoid leukemia. The treatment commonly involves chemotherapy and, if possible, allogeneic stem cell transplantation which is the only therapeutic option for long-term survival. Given the aggressive course of EMS, we here evaluated tyrosine kinase inhibitors as treatment options to delay disease progression...
September 7, 2017: European Journal of Haematology
https://www.readbyqxmd.com/read/28880088/brain-accumulation-of-ponatinib-and-its-active-metabolite-n-desmethyl-ponatinib-is-limited-by-p-glycoprotein-p-gp-abcb1-and-breast-cancer-resistance-protein-bcrp-abcg2
#15
Anita Kort, Stéphanie van Hoppe, Rolf W Sparidans, Els Wagenaar, Jos H Beijnen, Alfred H Schinkel
Ponatinib is an oral BCR-ABL1 inhibitor for treatment of advanced leukemic diseases that carry the Philadelphia chromosome, specifically containing the T315I mutation yielding resistance to previously approved BCR-ABL1 inhibitors. Using in vitro transport assays and knockout mouse models, we investigated whether the multidrug efflux transporters ABCB1 and ABCG2 transport ponatinib and whether they, or the drug-metabolizing enzyme CYP3A, affect the oral availability and brain accumulation of ponatinib and its active N-desmethyl metabolite (DMP)...
October 2, 2017: Molecular Pharmaceutics
https://www.readbyqxmd.com/read/28851502/overcoming-abc-transporter-mediated-multidrug-resistance-the-dual-role-of-tyrosine-kinase-inhibitors-as-multitargeting-agents
#16
Giovanni Luca Beretta, Giuliana Cassinelli, Marzia Pennati, Valentina Zuco, Laura Gatti
Resistance to conventional and target specific antitumor drugs still remains one of the major cause of treatment failure and patience death. This condition often involves ATP-binding cassette (ABC) transporters that, by pumping the drugs outside from cancer cells, attenuate the potency of chemotherapeutics and negatively impact on the fate of anticancer therapy. In recent years, several tyrosine kinase inhibitors (TKIs) (e.g., imatinib, nilotinib, dasatinib, ponatinib, gefitinib, erlotinib, lapatinib, vandetanib, sunitinib, sorafenib) have been reported to interact with ABC transporters (e...
August 3, 2017: European Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/28810255/ponatinib-induced-graft-versus-host-disease-graft-versus-leukemia-effect-in-a-patient-with-philadelphia-positive-acute-lymphoblastic-leukemia-without-the-t315i-mutation-relapsing-after-allogeneic-transplant
#17
Annamaria Petrungaro, Massimo Gentile, Carla Mazzone, Rosa Greco, Giuseppina Uccello, Anna Grazia Recchia, Laura De Stefano, Sabrina Bossio, Angela Palummo, Rosellina Morelli, Caterina Musolino, Fortunato Morabito, Ernesto Vigna
We describe the case of a patient with Philadelphia-positive acute lymphoblastic leukemia treated with dasatinib plus steroids as first-line therapy, who achieved a major molecular response (MMR) before undergoing matched, unrelated donor allogeneic stem cell transplant. Eleven months after the transplant, she experienced molecular relapse. Mutational screening showed negativity for the T315I mutation, The patient underwent a salvage chemotherapy regimen with clofarabine + cyclophosphamide + steroids and ponatinib (clofarabine 70 mg i...
August 16, 2017: Chemotherapy
https://www.readbyqxmd.com/read/28796569/cost-effectiveness-of-kinase-inhibitors-for-hematologic-malignancies-a-systematic-and-critical-review
#18
REVIEW
Monia Marchetti
Several genetic disruptions lead to constitutive activation of those kinases leukemic cells depend on for survival and proliferation. Kinase inhibitors (KI) are major therapeutic innovations for chronic myeloid leukemia (CML), chronic lymphoid leukemia (CLL) and myelofibrosis (MF) providing a relevant improvement of quality-adjusted survival in patients with high-risk or refractory disease. CML patients are being treated with first-generation KI imatinib since many years, achieving expected survivals longer than 10 years...
October 2017: Expert Review of Pharmacoeconomics & Outcomes Research
https://www.readbyqxmd.com/read/28781850/t315i-clone-selection-in-a-ph-all-patient-under-low-dose-ponatinib-maintenance
#19
Jasmine Noetzli, Mathilde Gavillet, Stavroula Masouridi-Levrat, Michel Duchosal, Olivier Spertini
We report here the clinical course of a Ph+ ALL patient who was treated with ponatinib 15 mg/day, as maintenance therapy, and developed a BCR-ABL T315I mutation leading to ALL relapse. This clonal evolution was reversed, without adverse effects, by increasing ponatinib to 45 mg/day. To our knowledge, we have been confronted with the first clinical case of a T315I clonal selection of ALL caused by subeffective therapeutic level of the drug. This single patient experience highlights the risk of T315I clone selection in Ph+ ALL treated with reduced dose ponatinib...
August 2017: Clinical Case Reports
https://www.readbyqxmd.com/read/28756527/synergistic-tumor-suppression-by-a-perilla-frutescens-derived-methoxyflavanone-and-anti-cancer-tyrosine-kinase-inhibitors-in-a549-human-lung-adenocarcinoma
#20
Amer Ali Abd El-Hafeez, Takashi Fujimura, Rikiya Kamei, Noriko Hirakawa, Kenji Baba, Kazuhisa Ono, Seiji Kawamoto
Anti-cancer tyrosine kinase inhibitors (TKIs) are effective in many types of cancers including non-small cell lung cancer, while appearance of TKI-resistant tumors suggests a need for the development of their potentiation strategies. We have previously shown that a methoxyflavanone derivative from the Asian medicinal herb Perilla frutescens (Perilla-derived methoxyflavanone; PDMF) shows a prominent anti-tumor activity against A549 human lung adenocarcinoma. Here we show that PDMF and anti-cancer TKIs (nilotinib, bosutinib, dasatinib, and ponatinib) synergistically suppress proliferation of A549 cells...
July 29, 2017: Cytotechnology
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