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

Iurlo, Alessandra; Cattaneo, Daniele; Consonni, Dario; Castagnetti, Fausto; Miggiano, Maria Cristina; Binotto, Gianni; Bonifacio, Massimiliano; Rege‐Cambrin, Giovanna; Tiribelli, Mario; Lunghi, Francesca; Gozzini, Antonella; Pregno, Patrizia; Abruzzese, Elisabetta; Capodanno, Isabella; Bucelli, Cristina; Pizzuti, Michele; Artuso, Simona; Iezza, Miriam; Scalzulli, Emilia; Barba, Gianluca; Maggi, Alessandro; Russo, Salvatore; Elena, Chiara; Scortechini, Anna Rita; Tafuri, Agostino; Latagliata, Roberto; Caocci, Giovanni; Bocchia, Monica; Galimberti, Sara; Luciano, Luigiana; Fava, Carmen; Foà, Robin; Saglio, Giuseppe; Rosti, Gianantonio; Breccia, Massimo

doi:10.3389/fphar.2023.1154377

Cited by 7 publications

(3 citation statements)

References 24 publications

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“…Furthermore, it is imperative to ensure the administration of an adequate TKI dose to mitigate the emergence of resistant clones and achieve TFR. However, long-term TKI therapy may lead to chronic adverse events (AEs) that can significantly impact patients' quality of life and contribute to morbidity and mortality ( 11 ). Consequently, dose reductions due to AEs are a routine aspect of TKI management ( 12 ).…”

Section: Discussionmentioning

confidence: 99%

“…Consequently, dose reductions due to AEs are a routine aspect of TKI management ( 12 ). Recent studies indicate that low-dose TKI therapy does not compromise the likelihood of attaining a DMR ( 11 , 13 ). However, the efficacy of low-dose TKI therapy is not extensively validated, and this approach is generally not recommended unless unavoidable, such as in cases of AEs.…”

Section: Discussionmentioning

confidence: 99%

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High Efficacy and Safety of Asciminib in a Chronic Myeloid Leukemia Patient with Chronic Kidney Disease Following Renal Transplantation

et al. 2024

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Chronic myeloid leukemia (CML) is a myeloproliferative neoplasm driven by the BCR::ABL1 tyrosine kinase. Tyrosine kinase inhibitors (TKIs) have been established as standard therapies for CML. However, some CML patients experience TKI intolerance. Asciminib was approved for CML patients either intolerant or refractory to TKI therapy. We herein report a 63-year-old CML patient who underwent renal transplantation and exhibited TKI intolerance. He was switched to asciminib, which achieved a deep molecular response without exacerbation of the renal function. Our experience revealed that asciminib is effective and safe for CML patients complicated with chronic kidney disease.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

High Efficacy and Safety of Asciminib in a Chronic Myeloid Leukemia Patient with Chronic Kidney Disease Following Renal Transplantation

et al. 2024

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“…The authors concluded that a low dose of TKI before treatment discontinuation does not seem to hamper the probability of achieving a DMR and, thus, the probability of maintaining the TFR. 33 …”

Section: Alternative Strategies With Respect To Tki Discontinuationmentioning

confidence: 99%

Twenty years of evolution of CML therapy: how the treatment goal is moving from disease to patient

Russo,

Malagola,

Polverelli

et al. 2023

Therapeutic Advances in Hematology

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The introduction of imatinib in 2000 opened the era of tyrosine kinase inhibitors (TKIs) for CML therapy and has revolutionized the life expectancy of CML patients, which is now quite like the one of the healthy aged population. Over the last 20 years, both the TKI therapy itself and the objectives have undergone evolutions highlighted and discussed in this review. The main objective of the CML therapy in the first 10 years after TKI introduction was to abolish the disease progression from the chronic to the blastic phase and guarantee the long-term survival of the great majority of patients. In the second 10 years (from 2010 to the present), the main objective of CML therapy moved from survival, considered achieved as a goal, to treatment-free remission (TFR). Two phenomena emerged: no more than 50–60% of CML patients could be candidates for discontinuation and over 50% of them molecularly relapse. The increased cumulative incidence of specific TKI off-target side effects was such relevant to compel to discontinue or reduce the TKI administration in a significant proportion of patients and to avoid a specific TKI in particular settings of patients. Therefore, the treatment strategy must be adapted to each category of patients. What about the patients who do not get or fail the TFR? Should they be compelled to continue the TKIs at the maximum tolerated dose? Alternative strategies based on the principle of minimal effective dose have been tested with success and they are now re-evaluated with more attention, since they guarantee survival and probably a better quality of life, too. Moving from treating the disease to treating the patient is an important change of paradigm. We can say that we are entering a personalized CML therapy, which considers the patients’ age, their comorbidities, tolerability, and specific objectives. In this scenario, the new techniques supporting the monitoring of the patients, such as the digital PCR, must be considered. In the present review, we present in deep this evolution and comment on the future perspectives of CML therapy.

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Treatment‐free remission as a new goal in the management of chronic myeloid leukemia: Clinical and biological aspects

Cattaneo,

Bucelli,

Bellani

et al. 2024

Hematological Oncology

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The therapeutic armamentarium of chronic myeloid leukemia (CML) has dramatically improved after small molecule tyrosine kinase inhibitors (TKIs) targeting BCR::ABL1 became available, with a life expectancy now close to that of the general population. Although highly effective, these drugs also have a toxicity profile that is often mild to moderate, but sometimes severe. Indeed, long‐term treatment with TKIs can lead to chronic adverse events that can negatively affect patients' quality of life and can promote significant morbidity and mortality, particularly in the case of second‐ or third‐generation TKIs. Treatment discontinuation has therefore become an emerging goal for CML patients and numerous studies have evaluated in off‐TKI subjects what requirements are appropriate for an attempt at treatment‐free remission (TFR). TFR eligibility is currently limited to a small population of subjects with both deep and sustained molecular responses to TKIs. For those attempting TFR, average success rates are promising, with 25%–30% of patients experiencing prolonged TFR. In case of failure to maintain sustained TFR, safety results to date are reassuring, with almost all patients responding successfully to resumption of TKIs, and advanced‐phase disease progression representing a very rare event. The purpose of this review is to discuss guidelines for TKI discontinuation, clinical advances from clinical trials and real‐life experiences, and describe areas of research, particularly regarding the biological factors capable of predicting the success of TFR.

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

Cited by 7 publications

References 24 publications

High Efficacy and Safety of Asciminib in a Chronic Myeloid Leukemia Patient with Chronic Kidney Disease Following Renal Transplantation

High Efficacy and Safety of Asciminib in a Chronic Myeloid Leukemia Patient with Chronic Kidney Disease Following Renal Transplantation

Twenty years of evolution of CML therapy: how the treatment goal is moving from disease to patient

Treatment‐free remission as a new goal in the management of chronic myeloid leukemia: Clinical and biological aspects

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