You are here

Dasatinib resistance, or suboptimal response?

Categories:

Hi CML community. My name is Chris (34) and I was diagnosed with CML chronic phase in September 2023.

BCR-Abl results to date:

12-Oct-23: 33%. Blasts at 4%. 100 mg Dasatinib started.
17-Nov-23: 17%
20-Dec-23: 9.7%
06-Feb-24: 3.4%
18-Apr-24: 1.5%
04-Jun-24: 1.7%
18-Jul-24: telephone call saying side ways movement. Expected to start the new TKI (likely, Asciminib on 19-Aug-24).

My consultant and I have agreed to change TKI. My preference is to opt for Asciminib over the other available TKIs.

Regarding my blood results, they are excellent, all parameters are in the normal range since April 24 and are stable. I also have zero side effects.

Given my blood results described by my consultant as excellent. My consultant and I are keen to keep the same trend going with the obvious exception to drive my Bcr-Abl into MMR.

Has anyone experienced their Bcr-Abl plateau above 1% and what happened next? I currently can't sleep at night due to worry and due to my background in science with a PhD in Immunology having actively worked with patients with haematological malignancies, namely, CLL and Multiple Myeloma, my experience with CML is pretty much non-existent. I hope your responses can help calm my mind.

NB. No mutations detected,

PS. I am finding it very difficult to be a patient.

Thank you in advance if you read this and respond to my post.

Hi Chris,

Welcome to the Forum.

Your Consultant has made the correct decision to switch TKI since you are still above 1% after nearly 12 months.

The good news is that you have no mutations, which means you could potentially try any of the other 5 TKI's. However, you haven't said which TKI you have tried so far, I assume it is Imatinib, which is the usual first line choice.

To be eligible for Asciminib, you would need to have tried 2 other TKI's first.

The second generation TKI's tend to achieve a quicker and deeper response.

The next TKI choice will depend on any other comorbitities you may have, for example if you have lung problems, then avoid Dasatinib or if you have cardiac or vascular issues, then avoid Nilotinib.

The CML journey can be difficult at times, especially when you have to decide to change treatment. I have tried 3 TKI's so far (Imatinib, Bosutinib and Dasatinib). I also never reached MMR (0.1%) on my first TKI (Imatinib). in fact it took me over 2 years to reach MMR and nearly 4 years to find the right TKI for me (Dasatinib). I am currently at 0.012% and have managed to reduce my dose to 50mg.

Don't despair at having to change TKI. On this forum you will see there are many slow responders like myself who have had to change TKI's. It's just a case of finding the right TKI for you.

Please keep in touch and let us know how you get on.

Take care.

James

Hi James, thank you for your kind reply. Oh you're right, I didn't put my TKI. I am on only 1 TKI and this is Dasatinib. I have not tried any other TKIs. Thank you for sharing your journey and experience. With all the various TKIs available it's really difficult to know what to do next on this journey.

Hi Chris,

It is interesting that your Consultant didn't try Imatinib first. Was there a reason for this? If not, it may be worth considering it since it has the most favourable side effect profile of all the TKI's. Although, I suspect your Consultant may want to try one of the other newer second generation TKI's to try and obtain a quicker and deeper response. The most likely candidates would be Nilotinib or Bosutinib. I wouldn't expect them to recommend Ponatinib as a 2nd line TKI choice unless you had the T315i mutation.

Your Consultant should discuss the pros and cons of each potential choice and advise which would be the most clinically appropriate for you.

Please get back in touch if you need any more help and let us know how you are getting on.

James

I had very similar results with dasatinib. I fluctuated from 0.5% to 1.0% over my first year or so.

Bosutinib got me to MMR twice but my case seems pesky and I switched to asciminib, where I still sit pretty consistently around 0.3 to 0.5.

My mental health has struggled alot due to CML. In my opinion, use your knowledge to see through your worry. Many studies show no difference in survival between CCyR (you're pretty much here) and MMR.

I've met with a specialist twice and it has very much eased my mind. I'd recommend you do the same, they deal with cases like ours all the time. Our consultants do not.

At the end of the day you still have 4 more drugs to try. One will stick. There are also three drugs that I know of in trial (olevermatinib, Tern-701, Elvn 001).

Thank you for your kind reply to my post. Thank you for sharing as this is reassuring to know our numbers are a little more challenging. I'll write back here when I know the TKI I'll switch too.

I'm sure too one will stick, but like you have said it's the mental health that needs some TLC. I try not to speculate on why my numbers have stalled, but it's tricky. Give it another 10 years and there will be another set of drugs available I am sure. The trial drugs you shared are a reminder that there is active pursuit to increase efficacy and safety of CML treatment.

Update: I'll be starting on Nilotinib 500 mg tomorrow with the last Dasatinib tonight.

Hi Chris,

Thanks for getting back to us.

Fingers crossed that Nilotinib gets your numbers lower soon and the frequency of Hospital appointments will reduce accordingly after the initial increase to check your bloods more often when changing TKI.

I haven't tried Nilotinib, so can't offer my personal experience, but I am sure you will get used to the fasting regime soon.

Take care,

James

DrFord how are you getting to 500 mg of Nilotinib? Is it two 150s and one 200? I started out with 800, it smacked me down for sure.
500 should be manageable.

Ah sorry my mistake I'm on 600 mg.

x2 150 mg in the morning
x2 150 mg in the evening.

I was on 600mg for a few months.
It was still a bit much for me.
I’m at 400 now and it’s better but I seemed to have developed hyperlipidemia and severe dry eye.
Keep an eye out for things as you adjust.
The hyperlipedemia caught me by surprise especially since I was doing a lot of fasting.

Good luck DrFord.

Thank you and take care. I hope everything moves in the right direction for you very soon!

Hi Chris

Sorry, I don't come on the forum that often so I only saw your post today. I just wanted to offer some thoughts / words of encouragement:

1) Since you're an academic, I'm sure you have access to lots of articles about CML, which can be both helpful and terrifying at the same timeL. I was studying at the time of my diagnosis in 2015 so I had access to almost every medical journal available and I spent hours and hours reading about this condition. It almost drove me crazy since there was so much to take in, and for every article I discovered that gave me hope, there were 5 others that discouraged me (especially those written before 2001, which I should never even have looked at). I remember consulting an ancient medical book called "The Modern Medical Counsellor" published in 1952 when I was first diagnosed, and its "treatment" guide was simply one sentence: "Curative treatment is impossible, so only palliative care can be advised until the inevitable outcome" - so much has changed since then, and it is an extremely treatable condition for the vast majority. So my advice is - don't worry too much (I know it's hard) and trust the medication and the science. There are a lot of options and asciminib has been extremely successful for those who are on it. I'm sure the nilotinib will work well for you as it works differently to the dasatinib.

2) It's not that uncommon to miss the milestones. Personally, it took me 24 months to get under 0.1% on dasatinib 100mg and there were many moments of worry. I have several friends with CML who were diagnosed around the same time as me, and those who were around my age (37 when diagnosed, 46 today) also seem to have responded slowly. In fact, I have a good friend who took 18 months to get below 1% and now, after FOUR years, has had his first result below 0.1%. He has not switched medication but stuck with the dasatinib 100mg all this time. I'm not a medical professional and I know that everyone is different, but I just wanted to share some hope that others have been through similar slow responses.

Best of luck and please keep us updated!

Best wishes

Martin

Hi Martin, thank you for your kind words of support and encouragement. It is reassuring to know my experience so far is not to dissimilar to yourself and your friends. Thank you for sharing and any new people who come across our thread may it also reassure them to read this.

My BCR-ABL result on 04.10.24 came back at 0.5% after switching from 100mg Dasatinib.

To re-cap:
23.04: 1.5%
04.06: 1.7%
26.07: 1.2%
22.08: 1.2% switched to Nilotinib.
04.10: 0.5%
next PCR on 11.11.

Hi Chris,

That's great news! I'm pleased that Nilotinib appears to be working and that your numbers are moving in the right direction. Fingers crossed that you reach MMR soon.

Take care

James

You’re making some big moves with Nilotinib. I had similar drops but not as wide on Nilotinib. Definitely let us know what happens on 11/11. If you keep it up you could pass MMR on this next test.