Comment on: “Switching TKIs during CML therapy is frequent, mostly driven by intolerance, and does not affect survival: a prospective Quebec registry study” by Busque et al.

OpenAlex İngilizce

I have read with great interest the study by Busque et al. [ 1 ], in which the authors evaluated the real-world data on switching patterns of tyrosine kinase inhibitors (TKIs) among a large population of chronic myeloid leukemia (CML) patients in Quebec, Canada. This study is very valuable since data on this topic is still limited in the literature, however, there still some points that need to be further underlined. The study reports that nearly half of the patients were switched to second-line TKI therapy with a median follow-up of approximately 6 years. The most common reason for switching was TKI-associated toxicities [ 1 ]. In the observational SIMPLICITY study, the proportion of patients with a TKI switch was lower than that observed in the study of Busque and colleagues, with the percentages of patients who were switched of an alternative TKI for the first and second years of therapy of 17.8 and 9.5%, respectively [ 2 ]. The update of the same study among European patients showed that, with a median follow-up of 5 years, 25% of patients were switched to second-line TKI therapy [ 3 ]. Similarly, intolerance was the most common reason for switching in the SIMPLICITY study. In the UK TARGET CML study, with a median follow-up of nearly 3 years, 44% of the patients were switched from first-line TKI [ 4 ], which was comparable to that of the Quebec registry [ 1 ]. In this study, resistance was the most common reason for switching, observed in 65% of the patients [ 4 ]. In patients with CML experiencing grade 4 or persisting grade 3 adverse events (AEs) under TKIs, the recommendation is to switch to an alternative treatment [ 5 , 6 ]. As the distribution of toxicity grades were not shared in the study of Busque et al. [ 1 ], maybe not all patients with a TKI switch due to intolerance had grade ≥3 AE. Generic TKIs are now globally available [ 7 , 8 ], and the rates of toxicities may differ between generics and the original molecule as well as between different generics [ 7 , 9 ]. In a previously published study also coming from Quebec, Canada, it was shown that switching to another TKI was higher in patients receiving generic imatinib when compared to those with branded imatinib and intolerance was the main reason for this higher non-persistence [ 10 ]. There was no data on the use of generics in the study of Busque et al. [ 1 ], and it would be interesting to see this information, together with the comparative data between generics and branded TKIs regarding rates of switching and other outcomes.