Dasatinib, nilotinib and standard-dose imatinib for the first-line treatment of chronic myeloid leukaemia: systematic reviews and economic analyses.

Pavey, Toby; Hoyle, Martin; Ciani, Oriana; Crathorne, Louise; Jones-Hughes, Tracey; Cooper, Chris; Osipenko, Leeza; Venkatachalam, M.; Rudin, C.; Ukoumunne, Obioha C; Garside, Ruth; Anderson, Rob

doi:10.3310/hta16420

Cited by 39 publications

(31 citation statements)

References 133 publications

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“…In our cases, more than half had molecular remission, major or profound, with one or more of the inhibitors employed. These figures coincide with those of other reports [25,26]. However, the OS is not affected by the existence of cytogenetic or molecular remission.…”

Section: Discussionsupporting

confidence: 92%

Long-Term Outcomes of Tyrosine Kinase Inhibitors Treatment for Chronic Myeloid Leukemia

M¹,

Zepeda²,

J³

et al. 2017

J Leuk

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Introduction:Chronic myeloid leukemia Ph+ (CML) is a myeloproliferative neoplasm that originates in a pluripotent and abnormal bone marrow cell, consistently associated with the BCR-ABL fusion gene, 1 located on the Ph chromosome, represents 15% of all leukemias. Treatment has evolved along with the disease using alkylators, antimetabolites, immunomodulators, and tyrosine kinase inhibitors (TKI), that have significantly improved patient survival, including ponatinib, effective for the T315I mutation.

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Section: Discussionsupporting

confidence: 92%

Long-Term Outcomes of Tyrosine Kinase Inhibitors Treatment for Chronic Myeloid Leukemia

M¹,

Zepeda²,

J³

et al. 2017

J Leuk

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“…In a similar analysis from the United Kingdom, imatinib followed by nilotinib was found to be the most cost-effective strategy with an incremental cost:utility ratio of £192 000/QALY. 25 A US-based analysis compared the use of generic imatinib at approximately 58% that of the brand name to physician's choice. For this purpose, physician's choice assumed an approximately equal distribution of patients among the three options (one-third of the patients each), and the use of 1 second-line TKI in all cases of resistance.…”

Section: Cost-effectivenessmentioning

confidence: 99%

Chronic myeloid leukemia: sequencing of TKI therapies

Cortes

Kantarjian

2016

Hematology

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Multiple tyrosine kinase inhibitors (TKIs) are available for managing patients with chronic myeloid leukemia. Although most patients have a favorable outcome with their initial therapy, whether imatinib or a second-generation TKI was used, some will require subsequent use of one or more different TKIs. Such sequencing might be indicated in a reactive way (ie, for patients who have experienced resistance or intolerance to their initial therapy) or in a proactive way (ie, for patients with a somewhat favorable outcome who have not reached an "optimal" outcome). Sequencing of TKIs has become standard practice, and the proper use of sequenced TKIs is likely to optimize outcomes and resource utilization. Learning Objectives• Assess the different scenarios in which TKI sequencing can be used in patients with chronic myeloid leukemia • Critically review the outcomes associated with sequencing of TKI in patients with chronic myeloid leukemia Tyrosine kinase inhibitors (TKIs) became standard therapy for patients with chronic myeloid leukemia (CML) not long after the first patient received STI571 (later known as imatinib mesylate) on a phase I clinical trial. 1 The initial approved indication was for patients with resistance to or intolerance of interferon alpha-based therapy, the standard at the time. By 2003, imatinib was approved as frontline therapy for CML, 2 and since then, nearly all patients with access to TKIs have received them as initial therapy. Shortly thereafter, secondgeneration agents, including dasatinib, nilotinib, and bosutinib, with increased potency, different structures that allowed them to overcome most mutations leading to resistance to TKIs, and different toxicity profiles, were introduced and eventually received regulatory approval. Later, ponatinib, a drug with activity against T315I and all mutations tested, proved effective in overcoming resistance in most patients, even those who had received 3 or more prior TKIs. All TKIs were eventually compared with imatinib in the first-line setting, and they generally demonstrated higher response rates, with deeper and faster responses which, in the case of dasatinib and nilotinib, were sufficient to lead to their approval as initial therapy for patients with chronic phase CML (CML-CP). This rapid development has resulted in the availability of multiple TKIs, and along with this, the sequential use of various TKIs in patients with CML-CP (Figure 1).The use of sequential TKI therapy, regardless of the choice of initial therapy, is perhaps more common than is usually appreciated. Despite the professed efficacy of initial therapy with TKIs, at least onethird of all patients initially treated in clinical trials with any TKI for newly diagnosed CML, whether imatinib or a second-generation TKI, have received at least one additional TKI. After 5 years of follow-up in the DASISION trial (in the final report), 39% of patients initially treated with dasatinib and 37% of those treated with imatinib are no longer receiving their initial therapy.3 Similarly, the 5-ye...

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“…Recent advances have led to the development of new tyrosine kinase inhibitors (TKIs) like dasatinib, nilotinib which give much better response than imatinib [6].…”

Section: Introductionmentioning

confidence: 99%

Performance of Sokal and Eutos Scores for Predicting Cytogenetic and Molecular Response in Newly Diagnosed Chronic Myeloid Leukemia-Chronic Phase Patients on Imatinib

Ganguly

Lakshmaiah

Jacob

et al. 2016

Indian J Hematol Blood Transfus

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Sokal index was developed in the pre-imatinib era to predict and prognosticate the outcome of Chronic myeloid leukemia (CML) patients. In the Imatinib era, a new scoring system called EUTOS scoring system has been validated as a predictive marker in CML. The scores have shown variable correlation with complete cytogenetic response (CCyR) and major molecular response (MMR). To assess the performance of Sokal score and EUTOS score as a predictive marker for CCyR and MMR for newly diagnosed CML-CP patients treated with TKIs. 273 patients with newly diagnosed CML were included in the study. They were treated with upfront imatinib. They were followed up for a median period of 3 years. Cytogenetic and Molecular response to the treatment were monitored regularly. Out of 273 patients, 174 patients (63 %) were having low EUTOS score and 99 (37 %) were having high EUTOS score. Patients with low, intermediate and high sokal scores were 237 (86.8 %), 28 (10.3 %) and 8 (2.9 %) respectively. 122 patients with low EUTOS score achieved CCyR within 18 months compared to 42 patients with high EUTOS score (p = 0.000).113 patients with low EUTOS score achieved MMR in 18 months compared to 33 patients with high EUTOS score (p = 0.000). 148, 14, 2 patients with low, intermediate and high Sokal score respectively have achieved CCyR in 18 months (p = 0.054). 133, 11, 2 patients with low intermediate and high sokal score respectively have achieved MMR in 18 months.(p = 0.06). EUTOS is better than Sokal score in predicting the outcome of patients of CML treated with imatinib.

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Dasatinib, nilotinib and standard-dose imatinib for the first-line treatment of chronic myeloid leukaemia: systematic reviews and economic analyses.

Cited by 39 publications

References 133 publications

Long-Term Outcomes of Tyrosine Kinase Inhibitors Treatment for Chronic Myeloid Leukemia

Long-Term Outcomes of Tyrosine Kinase Inhibitors Treatment for Chronic Myeloid Leukemia

Chronic myeloid leukemia: sequencing of TKI therapies

Performance of Sokal and Eutos Scores for Predicting Cytogenetic and Molecular Response in Newly Diagnosed Chronic Myeloid Leukemia-Chronic Phase Patients on Imatinib

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