Clinical Case Discussion Forum

This is a not uncommon case. In fact, Jane Apperley and I discussed this scenario very recently as experts on a South Asian video conference and we have slightly different opinions. This patient has achieved CCyR or 2-log/1% state after more than 2 years of imatinib. Ideally, you would want a 3-log/0.1% response or MMR by 1-1 and 1/2 years but not everyone achieves this. Jane considers this a suboptimal even failure response (anything less than 3-log). MD Anderson data published almost 10 years ago suggest that the 10-year survival with this response is nearly the same as someone with a 4-5 log reduction. I consider this a stable response, and I did not note that the patient was having any therapy-related issues.

The options therefore are to stay the course, which I favor, or a TKI switch. If the patient was having side effects, that would be an additional reason to consider a switch. A switch does not necessarily guarantee a deeper response, studies have shown that there may be new adverse events with a different drug, drug costs may be considerably higher even with a generic.

So long as the patient is molecularly stable with indefinite and consistent monitoring and has no QOL issues with imatinib, I would stay the course. Any worsening, then consider a switch to a properly remunerated second choice that is compatible with co-morbidities, if any.

What should not be done is any dose reduction, no TFR attempt at this level of response and no fishing expeditions. By the latter I mean, no mutation testing as with this response and stability, there is no likelihood of finding one.

This patient had several worrying features at diagnosis, including extramedullary disease (mainly mature neutrophilic deposits in the skin) plus a high Sokal score. We know that patients with a high Sokal receiving imatinib have a high risk of blast crisis - somewhere around 15% and I suspect her risk was even higher. On the other hand she has remained in chronic phase for over 2 years since therapy begun so her risk now is much lower - particularly because she has achieved CCyR and has on the whole a downwards tend in her BCR::ABL values. 

If this patient was under my care I would probably switch to a more potent TKI on the basis that her prospects of achieving TFR are quite poor if she remains on imatinib. I would probably switch to dasatinib 100 mg/day, lowering the dose to 50 mg/day once she has achieved MR4. If TFR was not a relevant goal for this patient then the argument for switching is less compelling. We have no evidence that a patient in CCyR on imatinib would have a lower risk of transformation if they switched to a more potent drug.

Access to TKIs beyond imatinib may be restricted in your region, but if she were to lose CCyR I would make every effort to get access to a second generation TKI or asciminib - after checking for a kinase domain mutation.

Tim Hughes has responded comprehensively and I agree with his advice. The presentation is very worrying so one question for you is whether you know that the patient had a typical transcript (e13a2, e14a2) at diagnosis, just to make sure you are monitoring accurately

I agree with Tim Hughes and Jane Apperley. At diagnosis, the risk of progression was very high due to this patient's high-risk ELTS and the extramedullary location of the disease. This could also be considered a prelude to an impending BC. After two years in CCyR with imatinib, the risk is lower but still present. In this case, it is advisable to try to reduce the residual disease as much as possible. If possible, I would switch to dasatinib.