ESH CML/MPN 2025 | Dose reduction of TKIs for TFR in patients with CML
In this video, Daniela Žáčková, MD, PhD, Masaryk University, Brno, Czechia, provides insight into her talk on the dose reduction of tyrosine kinase inhibitors (TKIs) for treatment-free remission (TFR) in patients with chronic myeloid leukemia (CML), highlighting the benefits of a gradual stepwise dose reduction approach over abrupt treatment discontinuation. This approach is also supported by findings from mathematical modeling and by data from patient surveys. This interview took place at the European School of Haematology (ESH) 4th How to Diagnose and Treat: CML/MPN meeting in Vienna, Austria.
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Transcript
Okay, so I presented the topic of dose reduction before attempting TFR, including presenting our own data. And this is actually a topic that is gaining increasing importance and also interest among the community as we know that both TKI dose reduction and discontinuation aim to address the challenges of long-term TKI therapy, I mean the intolerance, toxicity, decreasing adherence, increasing financial burden, etc...
Okay, so I presented the topic of dose reduction before attempting TFR, including presenting our own data. And this is actually a topic that is gaining increasing importance and also interest among the community as we know that both TKI dose reduction and discontinuation aim to address the challenges of long-term TKI therapy, I mean the intolerance, toxicity, decreasing adherence, increasing financial burden, etc. But we also know that abrupt treatment discontinuation is not or is far from being perfect because the TFR success rate is only about 50% after abrupt TKI discontinuation, and there are some adverse events which we didn’t expect at the beginning, called TKI withdrawal syndrome, and that also psychological aspects or issues are not very nice regarding the patient’s perceptions, feelings, etc.
So our idea was to design a trial that is different, with gradual stepwise dose reduction, and during my talk at the conference, I put this topic into the broader context of data that we already have and we know from the UK pivotal DESTINY trial and also from some real-world studies coming from Hammersmith Hospital in the UK and also from the Italian real-world CAMPUS study, that after such dose de-escalation, like preparation or bridge or something like this, the TFR rates appear higher than what I mentioned, about 70%, and that also some adverse events definitely go down.
So yeah, so I presented the overview. What is quite interesting is that this approach was also addressed in the interview or survey published by the Chinese group, and they showed that patients preferred such a gradual approach in comparison to abrupt treatment discontinuation, I mean from the full dose. And there are also quite interesting data on mathematical modeling coming from Dresden from colleagues led by Professor Reiter, showing us that particularly stepwise dose reduction was associated, or the model for it was associated, with the lowest probability of molecular recurrence, so there are data supporting this approach, so yeah, it was great to present and to discuss also with the community.
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Disclosures
Consultantancy: Angelini, Zentiva, Novartis; Speakers’ bureau: Angelini, Novartis, Scientific advisory board: Ascentage, Enliven Therapeutics, Novartis, Zentiva.
