Update on the management of Philadelphia chromosome positive chronic myelogenous leukemia: role of nilotinib

Emole, Josephine; Talabi, Taiwo; Pinilla‐Ibarz, Javier

doi:10.2147/btt.s67844

Cited by 9 publications

(9 citation statements)

References 64 publications

(75 reference statements)

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“…Since its approval in 2007, nilotinib has emerged as a remarkably effective and reasonably safe medication for the treatment of CML and other malignancies. 5,6 Its common and typically manageable side effects include fatigue, diarrhea, anorexia, abdominal discomfort, anemia, cough, and pruritus. Rare side effects include QT interval prolongation, congestive heart failure, and pancreatitis.…”

Section: Discussionmentioning

confidence: 99%

A Case of Severe, Nilotinib-Induced Liver Injury

et al. 2019

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Idiosyncratic hepatotoxicity is a leading reason for the discontinuation or dose modification of Food and Drug Administration (FDA)-approved medications in the United States. We report the case of a 53-year-old woman with chronic myeloid leukemia who developed acute cholestatic hepatitis in response to the tyrosine kinase inhibitor nilotinib. Nilotinib was discontinued, and the patient's liver function tests normalized over the next 3 months. We conclude that nilotinib may cause life-threatening hepatotoxicity and recommend that patients on the medication undergo regular monitoring of their liver tests.

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Section: Discussionmentioning

confidence: 99%

A Case of Severe, Nilotinib-Induced Liver Injury

et al. 2019

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“…Chronic myeloid leukemia (CML) is a myeloproliferative disorder which, if untreated, can lead to bleeding, infections, organ failure, and death [1]. Global CML incidence is 1-1.5 per 100,000 people [1], with Italy having a standardized incidence of 1.16 and 1.40 per 100,000 adult women and men, respectively [2].…”

Section: Introductionmentioning

confidence: 99%

Economic Model to Evaluate the Cost-Effectiveness of Second-Line Nilotinib Versus Dasatinib for the Treatment of Philadelphia Chromosome-Positive Chronic Myeloid Leukemia (CML-CP) in Italy

Bonifacio

Maheshwari

Tran

et al. 2021

PharmacoEconomics Open

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Objective The aim of this study was to evaluate the cost effectiveness of second-line nilotinib versus dasatinib for the treatment of Philadelphia chromosome-positive chronic myeloid leukemia (CML-CP) patients who are intolerant or resistant to imatinib and can transition to treatment-free remission (TFR). Methods A partitioned survival model was developed to compare the cost effectiveness of nilotinib versus dasatinib. The model was developed from the Italian healthcare payer perspective and included the following health states: on second-line tyrosine kinase inhibitor (TKI), off second-line TKI, accelerated phase/blastic crisis, TFR, and death. Progression-free and overall survival curves were derived from patient-level data that compared nilotinib and dasatinib as second-line therapy in CML-CP patients who were resistant or intolerant to imatinib. Drug costs, healthcare costs, and adverse event costs were based on real-world evidence and publicly available databases. Cost effectiveness was estimated over a 40-year time horizon. Scenario analyses were performed by adjusting time horizon, TFR parameters, costs, and utilities. Results Second-line nilotinib resulted in greater time spent in TFR (0.91 life-years), increased quality-adjusted life-years (QALYs) (1.89), increased life-years (2.16), and decreased per-patient costs (− 38,760 €). Therefore, nilotinib was strongly dominant compared with dasatinib in the base-case analysis. Nilotinib remained strongly dominant in most scenario analyses including shorter time horizon, exclusion of TFR, and varying TKI drug costs. Conclusions While the model showed that nilotinib treatment of imatinib-intolerant or resistant CML-CP patients was more effective and less costly than dasatinib treatment, there is considerable uncertainty in the findings.

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“…Despite the occurrence of this disease at any age, its incidence has a correlation with age. Given the high frequency of CML in men, the disease is commonly diagnosed in the sixth decade of life [ 1 , 2 ] . Studies have corroborated that in 95% of CML patients, reciprocal translocation t(9;22)(q34;q11) leads to the generation of the bcr-abl oncogene on truncated chromosome 22, known as Philadelphia chromosome.…”

Section: Introductionmentioning

confidence: 99%

“…Studies have corroborated that in 95% of CML patients, reciprocal translocation t(9;22)(q34;q11) leads to the generation of the bcr-abl oncogene on truncated chromosome 22, known as Philadelphia chromosome. Moreover, it produces a constitutively active tyrosine kinase that in turn promotes the development of CML [ 2 , 3 ] .…”

Section: Introductionmentioning

confidence: 99%

Assessment of Cannabinoids Agonist and Antagonist in Invasion Potential of K562 Cancer Cells

Gholizadeh

Ghahremani

Aliebrahimi

et al. 2019

ibj

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Background:The prominent hallmark of malignancies is the metastatic spread of cancer cells. Recent studies have reported that the nature of invasive cells could be changed after this phenomenon, causing chemotherapy resistance. It has been demonstrated that the up-regulated expression of matrix metalloproteinase (MMP) 2/MMP-9, as a metastasis biomarker, can fortify the metastatic potential of leukemia. Furthermore, investigations have confirmed the inhibitory effect of cannabinoid and endocannabinoid on the proliferation of cancer cells in vitro and in vivo. Methods:In the present study, the inhibitory effect of WIN 55212-2 (a CB1/CB2 receptor agonist) and AM251 (a selective CB1 receptor antagonist) on K562 cells, as a chronic myelogenous leukemia (CML) model, was evaluated using MTT and invasion assay. Expressions of MMP-2 and MMP-9 were then assessed by Western blot analysis.Results:The data obtained from MTT assay showed that WIN 55212-2 could attenuate cell proliferation; however, AM251 was less effective in this regard. Our results showed that WIN 55212-2 considerably reduced cancer cell invasiveness, while AM251 exhibited a converse effect. Moreover, CB1 activation resulted in decreased expression of MMP-2 and MMP-9. Conclusion:Our findings clarifies that CB1 receptors are responsible for anti-invasive effects in the K562 cell line.

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Update on the management of Philadelphia chromosome positive chronic myelogenous leukemia: role of nilotinib

Cited by 9 publications

References 64 publications

A Case of Severe, Nilotinib-Induced Liver Injury

A Case of Severe, Nilotinib-Induced Liver Injury

Economic Model to Evaluate the Cost-Effectiveness of Second-Line Nilotinib Versus Dasatinib for the Treatment of Philadelphia Chromosome-Positive Chronic Myeloid Leukemia (CML-CP) in Italy

Assessment of Cannabinoids Agonist and Antagonist in Invasion Potential of K562 Cancer Cells

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