Discontinuation Of Therapy

An important consideration is whether imatinib therapy can be safely discontinued for patients who have an adequate response (e.g., complete cytogenetic or molecular response) and if so when to do it. There is only limited published information in this regard, including case reports or small series.47-49 Two patients have been reported to have a sustained response after discontinuation of therapy. However, one series of three patients and one patient from another series have all lost their response after discontinuation of therapy following a complete molecular response. Interestingly, the responses were lost rapidly (i.e., within 3-6 months) after discontinuation of therapy, uncovering more rapid kinetics of the disease than are traditionally recognized. In at least two patients where imatinib was reinitiated, patients again rapidly responded, suggesting that resistance to imatinib had not evolved, but rather that continuation of therapy was required. It has been suggested that the earliest, probably quiescent, progenitor cells in CML are insensitive to imatinib in vitro.50 It is conceivable that these progenitors might trigger proliferation of leukemia once the inhibitory pressure of imatinib is eliminated. In view of these observations, even when limited, the current recommendation is to continue therapy with imatinib indefinitely.

Figure 18.1 Proposed treatment algorithm for patients with CML in early chronic phase. TKI, tyrosine kinase inhibitors)
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