Current Treatment Options for Chronic Myeloid Leukemia Patients Failing Second-Generation Tyrosine Kinase Inhibitors

García‐Gutiérrez, Valentín; Hernández-Boluda, Juan

doi:10.3390/jcm9072251

Cited by 15 publications

(16 citation statements)

References 54 publications

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“…In theory, the translocation mutation is an excellent target using tyrosine kinase inhibitors (TKIs); however, many patients fail to fully respond, with a decreased rate of recovery after each subsequent treatment [34]. Even though the majority of CML patients present with resistance and in some cases intolerance to TKIs such as nilotinib, dasatinib and bosutinib, this form of therapy remains mainstay for high-risk patients [35]. TKI treatment has been shown to have a direct effect on NK cell activity.…”

Section: Myeloid Leukemiamentioning

confidence: 99%

Natural Killer Cell-Mediated Immunotherapy for Leukemia

Allison

Mathews

Gilliland

et al. 2022

Cancers

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Leukemia is a malignancy of the bone marrow and blood resulting from the abnormal differentiation of hematopoietic stem cells (HSCs). There are four main types of leukemia including acute myeloid leukemia (AML), acute lymphoblastic leukemia (ALL), chronic myeloid leukemia (CML), and chronic lymphocytic leukemia (CLL). While chemotherapy and radiation have been conventional forms of treatment for leukemia, these therapies increase infection susceptibility, adverse side effects and immune cell inactivation. Immunotherapies are becoming promising treatment options for leukemia, with natural killer (NK) cell-mediated therapy providing a specific direction of interest. The role of NK cells is critical for cancer cell elimination as these immune cells are the first line of defense against cancer proliferation and are involved in both recognition and cytolysis of rapidly dividing and abnormal cell populations. NK cells possess various activating and inhibitory receptors, which regulate NK cell function, signaling either inhibition and continued surveillance, or activation and subsequent cytotoxic activity. In this review, we describe NK cells and NK cell receptors, functional impairment of NK cells in leukemia, NK cell immunotherapies currently under investigation, including monoclonal antibodies (mAbs), adoptive transfer, chimeric antigen receptor-NKs (CAR-NKs), bi-specific/tri-specific killer engagers (BiKEs/TriKEs) and future potential targets of NK cell-based immunotherapy for leukemia.

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Section: Myeloid Leukemiamentioning

confidence: 99%

Natural Killer Cell-Mediated Immunotherapy for Leukemia

Allison

Mathews

Gilliland

et al. 2022

Cancers

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“…Patients progressing to 3L treatment cannot be treated with the same TKI as was used in the 2L setting. Only bosutinib, nilotinib, dasatinib, and ponatinib are included as possible 3L therapies (other therapies were not included because of their low frequency of use in the 3L setting) [9][10][11]. The model cycle length is 1 month, and a half-cycle correction was used.…”

Section: Model Structurementioning

confidence: 99%

Cost-Effectiveness of Bosutinib for the Treatment of Adult Patients with Chronic Phase Chronic Myeloid Leukemia in the Second-Line Setting

Muresan¹,

Mamolo

Cappelleri

et al. 2021

Appl Health Econ Health Policy

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Background A recently conducted matching-adjusted indirect comparison demonstrated that bosutinib improved progressionfree survival, and delayed progression to advanced disease compared with dasatinib and nilotinib in patients with second line (2L) chronic-phase chronic myeloid leukemia (CP-CML). However, the long-term clinical and economic impact of using bosutinib versus dasatinib and nilotinib has not been evaluated. The objective was to determine the cost-effectiveness of bosutinib compared with dasatinib and bosutinib compared with nilotinib from a US payer perspective. Methods A cost-effectiveness model was developed using partition survival methods and three health states: progressionfree, progression, and death. Trial data (individual patient-level and aggregate-level data) informed the progression-free and overall survival estimates. Costs included drugs and medical resource use. Utility values were obtained from literature. Sensitivity analyses (SAs) included one-way and probabilistic sensitivity analyses (PSAs). Results Comparing bosutinib versus dasatinib resulted in a gain of 0.4 discounted life years, 1.5 quality-adjusted life years (QALYs), and incremental costs of $28,459 (values in 2020 US dollars), for an incremental cost-effectiveness ratio (ICER) of $19,811/QALY gained. Comparing bosutinib versus nilotinib resulted in a gain of 0.8 discounted life-years, 1.8 QALYs, and incremental costs of $76,563, for an ICER of $41,932/QALY gained. Drug costs and extrapolation distribution type were the main drivers of the model in the one-way SAs. In the PSAs, bosutinib had >90% and >80% probabilities of being cost-effective at a willingness-to-pay threshold of $100,000/QALY versus dasatinib and nilotinib, respectively. Conclusions Our results suggest that compared with dasatinib and nilotinib, bosutinib may represent good value for money for treating 2L CP-CML patients.

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“… 17 However, approximately 40% of patients do not respond to first‐line TKI treatment due to toxicity or lack of efficacy. 18 For patients failing the TKI first‐line treatment, a treatment change is mandatory to limit the risk of progression and death. CML is a paradigmatic model for analysis since a single chromosome aberration produces the leukemic phenotype, and its etiology is associated with the organization of the genome.…”

Section: Introductionmentioning

confidence: 99%

Large‐scale topological disruption of chromosome territories 9 and 22 is associated with nonresponse to treatment in CML

Fabián-Morales

Vallejo‐Escamilla

Gudiño

et al. 2021

Intl Journal of Cancer

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Chronic myeloid leukemia (CML) is a myeloproliferative neoplasm defined by the presence of t(9;22) translocation whose origin has been associated with the tridimensional genome organization. This rearrangement leads to the fusion of BCR and ABL1 genes giving rise to a chimeric protein with constitutive kinase activity. Imatinib, a tyrosine kinase inhibitor (TKI), is used as a first-line treatment for CML, though ~40% of CML patients do not respond. Here, using structured illumination microscopy (SIM) and 3D reconstruction, we studied the 3D organization patterns of the ABL1 and BCR genes, and their chromosome territories (CTs) CT9 and CT22, in CD34+ cells from CML patients that responded or not to TKI. We found that TKI resistance in CML is associated with high levels of structural disruption of CT9 and CT22 in CD34+ cells, increased CT volumes (especially for CT22), intermingling between CT9

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Current Treatment Options for Chronic Myeloid Leukemia Patients Failing Second-Generation Tyrosine Kinase Inhibitors

Cited by 15 publications

References 54 publications

Natural Killer Cell-Mediated Immunotherapy for Leukemia

Natural Killer Cell-Mediated Immunotherapy for Leukemia

Cost-Effectiveness of Bosutinib for the Treatment of Adult Patients with Chronic Phase Chronic Myeloid Leukemia in the Second-Line Setting

Large‐scale topological disruption of chromosome territories 9 and 22 is associated with nonresponse to treatment in CML

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