Molecular Resistance: An Early Indicator for Treatment Change?

Fava, Carmen; Kantarjian, Hagop M.; Cortés, Jorge E.

doi:10.1016/j.clml.2011.12.004

Cited by 7 publications

(6 citation statements)

References 88 publications

(111 reference statements)

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“…The half-life of nilotinib is 15 h. 16 Since food may affect nilotinib absorbtion, it is approved at a schedule of 400 mg twice daily without food for 2 hours before and 1 hour after administration. 24,29 Therapy with nilotinib is very well tolerated. The most commonly observed treatment-related nonhematologic AEs are rash, pruritus, and nausea.…”

Section: Nilotinibmentioning

confidence: 99%

Nilotinib as the First Line Therapy in Managing Chronic Myelogenous Leukemia

Setyawan

2021

eCL

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Abstrak: Leukemia mieloid kronis (chronic myeloid leukemia/CML) adalah penyakit klonal dari sel induk hematopoietik, secara sitogenetik ditandai dengan adanya kromosom Philadelphia (t[9,22][q34;q11]), yang merupakan fusi BCR-ABL1 onkogen. Nilotinib, generasi kedua inhibitor kinase tirosin, merupakan turunan aminopirimidin yang menghambat aktivitas kinase tirosin protein BCR-ABL. Dengan aktivitas penghambatan yang 10-60 kali lebih besar daripada imatinib, pada terapi lini pertama standar untuk CML, nilotinib efektif untuk CML fase kronik dan akselerasi yang resisten terhadap imatinib, namun terapi kombinasi nilotinib dengan agen lainnya masih diperlukan untuk pasien dengan CML krisis blas. Nilotinib aktif terhadap beberapa mutan BCR-ABL yang resisten terhadap imatinib, kecuali mutan T315I. Mutasi spesifik E255K/V, Y253H/F, F359C/V, dan L248V umumnya kurang sensitif terhadap nilotinib. Sebagai terapi lini pertama pada pasien CML fase kronik dengan Ph+ yang baru terdiagnosis, nilotinib menunjukkan CCyR dan MMR yang lebih tinggi serta pengembangan menjadi fase akselerasi/krisis blas serta resiko kematian yang lebih rendah, bila dibandingkan dengan imatinib. Simpulan penelitian ini ialah nilotinib lebih unggul dibandingkan dengan imatinib sebagai terapi lini pertama pada pasien CML fase kronik dengan Ph+ yang baru terdiagnosis,Kata kunci: chronic myeloid leukemia (CML), nilotinib, imatinib, terapi lini pertama Abstract: Chronic myeloid leukemia (CML) is a clonal disease of the hematopoietic stem cells, cytogenetically characterized by Philadelphia chromosome (t[9,22][q34;q11]) leading to the fusion of BCR-ABL1 oncogene. Nilotinib, the second-generation tyrosine kinase inhibitor (TKI), is an aminopyrimidine derivative that inhibits the tyrosine kinase activity of the chimeric protein BCR-ABL. Its inhibitory activity is 10-60 times that of imatinib, therefore, as the standard first-line therapy for CML, nilotinib is effective in the case of CML-CP and CML-AP with imatinib resistant or intolerant. Albeit, novel approaches with nilotinib-based combinations are required for patients in CML-BP. Nilotinib is active against several imatinib-resistant BCR-ABL mutants with the exception of T315I. Specific mutations that are less sensitive to nilotinib include E255K/V, Y253H/F, F359C/V, and L248V. As the first-line therapy of patients with newly diagnosed Ph+ CML-CP, nilotinib has higher rates of CCyR and MMR, lower rates of progression to AP or BC, and lower risk of CML related death when compared with imatinib. In conclusion, nilotinib is superior to imatinib as the the first-line therapeutic option in newly diagnosed Ph+ CML-CP patients.Keywords: chronic myeloid leukemia (CML), nilotinib, imatinib, first line therapy

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Section: Nilotinibmentioning

confidence: 99%

Nilotinib as the First Line Therapy in Managing Chronic Myelogenous Leukemia

Setyawan

2021

eCL

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“…He was induced with hyper-CVAD and ponatinib (30 mg, qd). After 5 courses of hyper-CVAD plus ponatinib, the patient achieved a partial cytogenetic remission with a bone marrow karyotype of 46,XY,t(9;22)(q34;q11.2) [12]/46,XY [8] and a percentage of b2a2 BCR-ABL1 to ABL1 transcripts of 97.29 in peripheral blood. He is currently waiting for allogeneic hematopoietic stem cell transplantation.…”

Section: Casementioning

confidence: 99%

“…There is no previous report of T315I mutation in CML cases arising in a background of previous MPNs. T315I is relatively rare but is highly TKI resistant [12,13].…”

Section: Casementioning

confidence: 99%

Chronic myelogenous leukemia in patients with MPL or JAK2 mutation‐positive myeloproliferative neoplasm

Chen

Wang

Verstovšek

et al. 2015

Int J Lab Hematology

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“…Nilotinib (Novartis) is a second-generation TKI targeting c-KIT, PDGFR-A and PDGFR-B and is indicated for patients with CML who are resistant or intolerant to imatinib [11]. Recent studies have reported that dasatinib and nilotinib show efficacy as first-line therapies, and both have been approved in the US-FDA for newly diagnosed, chronic-phase CML [24].…”

Section: Imatinibmentioning

confidence: 99%

Molecularly Targeted Therapy: Past, Present and Future

Dobashi

Goto²,

Kimura³

et al. 2012

Chemotherapy

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Cancer is a heterogeneous disease with diverse underlying molecular causes and equally diverse clinical profiles. It has long been a goal to develop cancer therapies that would be distinct and appropriate for each patient. The recent concept of "oncogene addiction" has been very helpful in guiding this path "from the bench to the bed". The most significant advance in the treatment of cancer in the past few decades has been the introduction of molecularly targeted therapies, such as imatinib for chronic myelogenous leukemia and gefitinib for lung cancer. In addition, many new promising agents have been developed in the laboratory and are now entering clinical testing. Thus, our current challenge is to better understand how to utilize these agents in clinical practice and to better understand the mechanisms of drug resistance that may be encountered. Advances in these areas would allow for more targeted and effective treatment options for cancer patients. This review describes the development of molecularly targeted therapies from the past achievements to current efforts, the insights learned by this effort, the problems encountered in the clinic, and the potential for novel development of next-generation kinase inhibitors.

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Molecular Resistance: An Early Indicator for Treatment Change?

Cited by 7 publications

References 88 publications

Nilotinib as the First Line Therapy in Managing Chronic Myelogenous Leukemia

Nilotinib as the First Line Therapy in Managing Chronic Myelogenous Leukemia

Chronic myelogenous leukemia in patients with MPL or JAK2 mutation‐positive myeloproliferative neoplasm

Molecularly Targeted Therapy: Past, Present and Future

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