Thursday, November 30, 2023
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Although imatinib is an excellent drug based on the IRIS data, the Hammersmith data and the study by Lucas et al.[7] suggest that long-term results are not as favorable. Based on the Hammersmith data, roughly one-third of patients will not have the response that one would hope for. The data reported by Lucas et al.[7] suggest that only approximately half of the patients treated with imatinib in a community setting would be expected to have a sustained positive outcome. Imatinib is generally well tolerated. Certainly, if it is compared with IFN-α, then its side-effect profile is very favorable. However, although most of its nonhematologic side effects are grade 1 or 2, they could significantly affect quality of life in the long run. For instance, if given the choice, most patients would certainly want to avoid a lifetime of grade 1/2 diarrhea.
The most important argument in favor of using dasatinib or nilotinib in first-line therapy is the fact that with both agents, the response milestones (CCyR and MMR) are achieved earlier and in more patients than with imatinib. Long-term follow-up data clearly show that patients who achieve these milestones earlier have the best outcomes. The IRIS data suggest that once a TKI is started, there is a window of 2 to 3 years during which the risk of disease progression or transformation is highest. The ENESTnd and DASISION studies strongly suggest that nilotinib and dasatinib decrease the risk of disease progression, certainly up to the point of analysis. This outcome is not unexpected, because they have a broader spectrum of activity as far as resistance- imparting mutations are concerned. Although a blast transformation has become a relatively rare event in the TKI era, this outcome is devastating for patients. Casting a wider net with dasatinib or nilotinib to diminish the risk of disease progression early on is certainly a sound strategy. These agents do not have the track record of sustained response that imatinib has. Technically, one cannot extrapolate to dasatinib and nilotinib the observations on the 2- to 3-year “window of opportunity” that have been made with imatinib. However, currently no data suggest that they would not be similar in that respect. Finally, based on available data, one could predict that fewer patients started on dasatinib or nilotinib will require salvage therapy than those started on imatinib.
