Clinical trials have identified factors that predict a successful (i.e. long-lasting) TFR, such as response to first-line TKI, duration of TKI treatment and duration of deep molecular remission. Further analyses have suggested several other factors.
Early molecular response (i.e. low BCR–ABL1IS) is associated with a better prognosis. Ratios over 10% at 3 months were associated with shorter progression-free and overall survival in trials of dasatinib.
Type of TKI. Most studies suggest that the molecular response rate is higher with the second-generation TKIs, so more patients become eligible for attempting TFR. However, results from the trials of imatinib and the second-generation TKIs discussed above indicate that a longer TFR achieved by the use of second-generation TKIs does not always translate into longer overall survival. It is therefore important to consider whether any adverse effects of the TKIs may compromise survival compared with that expected based on their molecular response.
Risk stratification. Several scoring systems can be used to stratify the risk of chronic myeloid leukaemia (CML), including Sokal, EUTOS and EURO. Sokal is perhaps the best known and takes into account the patient’s age, spleen size, blast count and platelet count. While the STIM trial seemed to show some correlation between duration of TFR and Sokal score, most trials since, including the large EURO-SKI trial, have not shown an association between TFR success and Sokal score.
