Adverse events of tyrosine kinase inhibitors and their impact on quality of life in patients with chronic myeloid leukemia

Introduction: Patients reported outcome (PRO) are still under-used in patients with chronic myeloid leukemia (CML) treated with tyrosine kinase inhibitors (TKIs), though data on the correlation between quality of life (QoL) and therapeutic efficacy are increasingly known. Chronic low-grade toxicities can reduce patient's QoL and negatively impact on adherence. Areas covered: This review will focus on the role of QoL questionnaires in patients with CML, receiving imatinib or newer TKIs (dasatinib, nilotinib, bosutinib, ponatinib). Physicians tend to underestimate the impact of TKI-related symptoms, in particular fatigue, that negatively affect QoL and can be a reason of poor adherence to therapy, with detrimental effect on long-term response. Few studies pointed out the role of PRO in CML, and there is paucity of questionnaires specifically designed for CML patients. Expert commentary: We recommend a wider use of PRO to join the pursuit of a rapid and deep responses with an optimization of QoL.ARTICLE HISTORY

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“…As a matter of fact, with such effective therapies the QoL of CML patients is impacted more by side effects of TKIs than by disease itself [64].…”

Section: Five-year Viewmentioning

confidence: 99%

How could patient reported outcomes improve patient management in chronic myeloid leukemia?

Marchi

Medeot

Fanin

et al. 2016

Expert Review of Hematology

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“…), whereas some appear as a class-effect. Also the potentially serious AEs of these newer TKIs might even be more hazardous than beneficial in a proportion of patients leading to both treatment interruption and/or discontinuation and these AEs might have negative impacts on adherence and health-related quality of life (HRQoL) [7].…”

Section: Introductionmentioning

confidence: 99%

Tyrosine kinase inhibitor (TKI) therapy for newly-diagnosed patients with chronic myeloid leukemia: focusing on TKI discontinuation due to adverse events – is better always good?

Eşkazan

Özmen

2017

Expert Review of Hematology

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“…53 These haematological complications can lead to other AEs such as fatigue in patients with anaemia, opportunistic infections in those with leucopenia or neutropenia, and risk of bleeding associated with thrombocytopenia. 54 Typically, myelosuppression occurs during the initiation of treatment, when a hypocellular marrow frame is observed; however, this phenomenon is rapidly reversed. All treatments are listed in alphabetical order.…”

Section: Discussionmentioning

confidence: 99%

Haematological adverse events associated with tyrosine kinase inhibitors in chronic myeloid leukaemia: A network meta‐analysis

Fachi

Tonin

Leonart

et al. 2019

Brit J Clinical Pharma

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Despite their overall favourable safety profile, tyrosine kinase inhibitors (TKIs) are related to severe adverse events including haematological toxicities such as anaemia, leucopenia, neutropenia and thrombocytopenia. We designed a systematic review and network meta-analysis of randomised controlled trials to compare safety among TKIs (bosutinib, dasatinib, imatinib, nilotinib, ponatinib and radotinib) used by patients diagnosed with chronic myeloid leukaemia. Methods: We obtained data from the PubMed, Scopus, Web of Science, and SciELO databases. The Bayesian approach was used for direct and indirect comparisons, and the treatments were ranked by the surface under the cumulative ranking curve (SUCRA). Results: Seventeen studies were included in the network meta-analysis. Our data show that dasatinib was generally considered worse than the other TKIs, with SUCRA values for 140 mg dasatinib of 90.3% for anaemia, 87.4% for leucopenia, 90.6% for neutropenia and 97.2% for thrombocytopenia. In addition, nilotinib was shown to be safer, with SUCRA values for 600 and 800 mg doses of 21.9 and 35.8% for anaemia, 23.8 and 14.6% for leucopenia, 33.0 and 17.7% for neutropenia, and 28.7 and 32.6% for thrombocytopenia, respectively. Conclusion: Dasatinib appeared as the least safe drug for chronic myeloid leukaemia, probably because it binds to multiple key kinase targets, being more prone to cause serious haematological adverse events. Nilotinib demonstrated a safer profile, mostly due to its selective binding capacity. KEYWORDS chronic myeloid leukaemia, drug-related side effects and adverse reactions, network meta-analysis, tyrosine kinase inhibitors 1 | INTRODUCTION Tyrosine kinase inhibitors (TKIs) represent a milestone in chronic myeloid leukaemia (CML) treatment. Although these drugs are effective and have an overall favourable safety profile with mild to moderate adverse events (AEs), they can also cause severe events including haematological AEs, such as anaemia, leucopenia, neutropenia and thrombocytopenia, which occur due to myelosuppression. Moreover, The authors confirm that the PI for this paper is Roberto Pontarolo and that he had responsibility for this review.

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Adverse events of tyrosine kinase inhibitors and their impact on quality of life in patients with chronic myeloid leukemia

Cited by 16 publications

References 61 publications

How could patient reported outcomes improve patient management in chronic myeloid leukemia?

How could patient reported outcomes improve patient management in chronic myeloid leukemia?

Tyrosine kinase inhibitor (TKI) therapy for newly-diagnosed patients with chronic myeloid leukemia: focusing on TKI discontinuation due to adverse events – is better always good?

Haematological adverse events associated with tyrosine kinase inhibitors in chronic myeloid leukaemia: A network meta‐analysis

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