The case is certainly a challenging one.
In response to your questions:

1. I would be quite suspicious that nilotinib is exacerbating her MS. Certainly enough suspicion to suggest that you shouldn’t use nilotinib any more.

2. I think it would be perfectly reasonable to attempt TFR now since you are forced to stop nilotinib and want to avoid a TKI if at all possible in case it is a class effect. Her chances of successful TFR are not high because she developed resistance to imatinib and has only had MR4 for about 2 years on nilotinib. So chances may only be 20% but you don’t lose a lot by trying. At least she gets a break for a few months which may be informative regarding symptoms.

3. With IM and NIL out of the picture I agree it is between dasatinib and ponatinib if you have to restart. You would hate to add vascular problems to her current neurological deficit so I would choose dasatinib. Have you searched for MS in the dasatinib setting? I haven’t heard of it. The alternative would be ABL001 which would be fine as long as the MS progression isn’t due to ABL inhibition which seems unlikely. Is that a practical option? Is the Phase III third line study of ABL001 versus bosutinib coming to Melbourne?

I have a 56yo patient who was diagnosed CML-CP in 2010.
Conventional Ph chr and bcr-abl p210

Commenced Imatinib (IM)
Achieved >4 log reduction in bcr-abl…but then late r lost this response and converted to nilotinib (NIL) by early 2014

The interesting part is that the patient has multiple sclerosis (MS).

From neurologist – he has high clinical suspicion that her MS has been exacerbated, both in terms of frequency and severity since starting NIL

There is no doubt conceptually, MOA via TK-dep pathways - particularly PDGFR, c-kit, SRC – this is certainly feasible
Interesting there are mouse models looking at IM in MS and other autoimmune diseases

It has also been a particular cold winter in Melbourne!

It terms response to NIL.
Commenced late 2013/early 2014 – has achieved >4-log reduction (pretty quickly) and sustained since

So our questions

1. What is the likelihood of this association with nilotinib and exacerbation of MS?

2. Safety of considering trial cessation NIL

3. Alternative TKI…lesser of evils given her comorbidity 9Das and PON are also potent inhibitor PDGFR, c-Kit, SRC)