Various strategies might improve the odds of drug-free remission of CML, and some of these have already been used in clinical trials. Given the excellent safety and tolerability of TKI therapy, the safety of any novel treatment for this patient group is of paramount importance. Any augmentation of TKI therapy must carry a risk of new, additional, or unexpected toxicity, and this risk must be balanced against the potential benefit. The same consideration of patient safety applies to a therapeutic test of TKI withdrawal. It is essential that careful monitoring is undertaken to detect relapse as early as possible so that effective TKI therapy may be reinstituted. It is therefore recommended that, at present, such approaches are only considered in the context of carefully designed, controlled clinical trials.
Sustained CMR after withdrawal of TKIs is a therapeutic success that many clinicians and scientists would not have anticipated when IM treatment was first introduced. By analogy with the treatment of HIV with antiretroviral drugs, it seemed likely that even a highly effective targeted treatment would need to be continued indefinitely to suppress the CML clone. Perhaps contrary to expectation, this is not always the case in chronic-phase CML. Early and deep response translates to long-term disease control with the potential for safe withdrawal of treatment in carefully selected patients. The challenges now are to identify those patients in whom treatment can safely be withdrawn, and to increase the number of patients eligible for withdrawal of therapy.