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. 2023 Mar 23:14:1154377.
doi: 10.3389/fphar.2023.1154377. eCollection 2023.

Treatment discontinuation following low-dose TKIs in 248 chronic myeloid leukemia patients: Updated results from a campus CML real-life study

A Iurlo  1 , D Cattaneo  1   2 , D Consonni  3 , F Castagnetti  4 , M C Miggiano  5 , G Binotto  6 , M Bonifacio  7 , G Rege-Cambrin  8 , M Tiribelli  9 , F Lunghi  10 , A Gozzini  11 , P Pregno  12 , E Abruzzese  13 , I Capodanno  14 , C Bucelli  1 , M Pizzuti  15 , S Artuso  1 , M Iezza  4 , E Scalzulli  16 , G La Barba  17 , A Maggi  18 , S Russo  19 , C Elena  20 , A R Scortechini  21 , A Tafuri  22 , R Latagliata  23 , G Caocci  24 , M Bocchia  25 , S Galimberti  26 , L Luciano  27 , C Fava  28 , R Foà  16 , G Saglio  28 , G Rosti  29 , M Breccia  16
Affiliations

Treatment discontinuation following low-dose TKIs in 248 chronic myeloid leukemia patients: Updated results from a campus CML real-life study

A Iurlo et al. Front Pharmacol. .

Abstract

TKIs long-term treatment in CML may lead to persistent adverse events (AEs) that can promote relevant morbidity and mortality. Consequently, TKIs dose reduction is often used to prevent AEs. However, data on its impact on successful treatment-free remission (TFR) are quite scarce. We conducted a retrospective study on the outcome of CML subjects who discontinued low-dose TKIs from 54 Italian hematology centers participating in the Campus CML network. Overall, 1.785 of 5.108 (35.0%) regularly followed CML patients were treated with low-dose TKIs, more frequently due to relevant comorbidities or AEs (1.288, 72.2%). TFR was attempted in 248 (13.9%) subjects, all but three while in deep molecular response (DMR). After a median follow-up of 24.9 months, 172 (69.4%) patients were still in TFR. TFR outcome was not influenced by gender, Sokal/ELTS risk scores, prior interferon, number and last type of TKI used prior to treatment cessation, DMR degree, reason for dose reduction or median TKIs duration. Conversely, TFR probability was significantly better in the absence of resistance to any prior TKI. In addition, patients with a longer DMR duration before TKI discontinuation (i.e., >6.8 years) and those with an e14a2 BCR::ABL1 transcript type showed a trend towards prolonged TFR. It should also be emphasized that only 30.6% of our cases suffered from molecular relapse, less than reported during full-dose TKI treatment. The use of low-dose TKIs does not appear to affect the likelihood of achieving a DMR and thus trying a treatment withdrawal, but might even promote the TFR rate.

Keywords: chronic myeloid leukemia; low dose; outcome; resistance; treatment-free remission; tyrosine kinase inhibitors.

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Conflict of interest statement

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Figures

FIGURE 1
FIGURE 1
Treatment-free remission (TFR) after tyrosine kinase inhibitor (TKI) therapy (Kaplan-Meier survivor function).
FIGURE 2
FIGURE 2
Treatment-free remission (TFR) after tyrosine kinase inhibitor (TKI) therapy (Kaplan-Meier survivor function) according to resistance to previous TKIs.
See this image and copyright information in PMC

References

    1. Bower H., Björkholm M., Dickman P. W., Höglund M., Lambert P. C., Andersson T. M. (2016). Life expectancy of patients with chronic myeloid leukemia approaches the life expectancy of the general population. J. Clin. Oncol. 34, 2851–2857. 10.1200/JCO.2015.66.2866 - DOI - PubMed
    1. Breccia M., Abruzzese E., Stagno F., Iurlo A., Pane F., Attolica I., et al. (2021). First interim analysis of the Italian dante study: De-escalation before treatment-free remission in patients with chronic myeloid leukemia treated with first-line nilotinib. Blood 138, 1474. 10.1182/blood-2021-145411 - DOI
    1. Campbell V. E., Copland M. (2013). Dasatinib for the treatment of chronic phase chronic myeloid leukemia. Clin. Pract. 10, 415–425. 10.2217/cpr.13.43 - DOI
    1. Cayssials E., Torregrosa-Diaz J., Gallego-Hernanz P., Tartarin F., Systchenko T., Maillard N., et al. (2020). Low-dose tyrosine kinase inhibitors before treatment discontinuation do not impair treatment-free remission in chronic myeloid leukemia patients: Results of a retrospective study. Cancer 126, 3438–3447. 10.1002/cncr.32940 - DOI - PubMed
    1. Clark R. E., Polydoros F., Apperley J. F., Milojkovic D., Pocock C., Smith G., et al. (2017). De-escalation of tyrosine kinase inhibitor dose in patients with chronic myeloid leukaemia with stable major molecular response (DESTINY): An interim analysis of a non-randomised, phase 2 trial. Lancet Haematol. 4, e310–e316. 10.1016/S2352-3026(17)30066-2 - DOI - PubMed

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