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When to switch to asciminib

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I am wondering if others here feel that a switch to asciminib is warranted for my situation.

After my most recent appointment, my doctor put the wheels in motion to switch me to asciminib while we waited for my test results. This was based on my previous test which had a jump from 0.06 to 0.2%.

Fast forward to today. My prescription for asciminib showed up at my door, I have only a few days of bosutinib left, and I receive the results from my last test which technically puts me back into MMR.

My doctor feels that my results to date are "wishy washy" and wants to make the switch regardless of MMR. I suppose he prefers that I be at a DMR after 2+ years, or at a minimum stable in MMR.

He did consult a specialist after my results at 23 months (0.2%), and the specialist agreed that ponatinib or asciminib should be prescribed.

My only fear in all of this is exhausting another treatment option if it is not warranted now.

3 -1.62 2.40% -> Dasatinib
5 -2.39 0.41%
8 -2.15 0.71%
9 -2.00 1.00%
11 -2.33 0.47%
13 -2.19 0.65% -> Switch to Bosutinib
15 -2.40 0.40%
17 -2.30 0.50%
20 -3.20 0.06%
23 -2.68 0.21%
26 -3.02 0.10% -> ?????????????

Granted I've had a slow response, but your values don't look that bad to me. You are pretty much MMR with one blip. Getting to MMR at roughly 20 months is faster than I got there and I remained on Sprycel the whole time. Unless you have had issues with side effects from Bosutinib I'd recommend waiting at least another test before trying a new medication. I'm somewhat surprised the specialist recommended changing medications at 23 months. I've had a similar situation and the specialist recommended waiting longer unless the medication was adversely effecting me. That said, if you want to change medications to see how you respond and the doctor gives you the option to go back to Bosutinib if ascimib doesn't work well for you then that may not be a bad approach either. Good luck!

Ian

You have a nice downwards trend, into MMR. That's your primary treatment goal which has been achieved. Congratulations!

I see no good reason to change medication from an efficacy point of view. Stick with it - it looks like it's working for you. We can't all be super-fast responders (I sure wasn't) but there's no long-term benefit from being a fast vs a slow responder. The response is all that matters.

David.

Thanks for the kind insight Ian and David. To be honest I was ready to make the switch after the jump I had at 23 months.

I was holding out some hope that my results at 26 months would be back earlier and in MMR, possibly changing my doctor's opinion. That didn't work out as I didn't have a reserve of bosutinib, so I've had to make the switch.

My next appointment is in a month. I'm doubtful that he would advise switching back to bosutinib by that point.

I guess there's really not much to be worried about. If bosutinib was going to continue to give me decent results, changes are asciminib will be the same or better.

Hi. I’m curious about side effects of bosutinib as I recently made the switch to Asciminib myself (after failing bosutinib and dasatinib).

I will tell you that the change is like night and day. It seems that I am earlier in my treatment course (diagnosed in April 2023), but the side effects from bosutinib and dasatinib were dramatic. I feel so much better on Asciminib. For what it’s worth.

Wishing you lots of luck and good health.

Olivia

Glad to hear that you are tolerating this one well! I didn't have any side effects with dasatinib or bosutinib, and the trend has continued for me with asciminib.

Hi Olivia, how much asciminib you’ve been taking and is it working?

Hi, I’ve been taking 2 40mg tabs once a day when I first wake up. It’s been so above and beyond with side effects compared to the other TKIs! A little nausea, a little myalgia, but nothing I can’t tolerate. Keep us posted!

Hi again! Just wanted to let all who are curious know that, after 14 months on TKIs, including bosutinib and dasatinib with suboptimal results, as of today my PCR is 0.000%!!! If asciminib is available to you and your doctor is recommending it, I strongly encourage you to try. I had not reached MMR until switching to asciminib at 10 months out from diagnosis, and my PCR shot down from 3% to 2% to 0.075% to now 0% in just 4 short months. I also have a mutation in ASXL1, for reference. Keep fighting the good fight!!!

That’s fantastic! You must celebrate.

David.

Thank you! Doing a little jig!

Hi and thanks for sharing the dose info and good news. I’m seeing my doc in June and will ask him to switch as I don’t tolerate Nilotinib well, started experiencing heart racing and thumping after meals, while on Dasatinib I started getting respiratory infections once a month throughout 2023.

I was on 400 mg Nilotinib from January to March and then tried 600 mg in April, but heart racing got more severe. On top of that, I also gained additional 6 kilos in just 4 months.

While on 400 mg Nilotinib and 50 mg Dasatinib, 15 April to 15 May, I got another infection, this time a tooth one, so had to stop Dasatinib.

I did a bit of research on how Nilotinib leads to cardiovascular disease (insulin resistance -> glucose disorders -> lipids disorders) and it seems it happens to 80% of patients who take 600 mg or more pd and/or take it for 5+ years, so figured out it’s probably not the best long term option.

https://www.frontiersin.org/articles/10.3389/fcvm.2022.966182/full
https://onlinelibrary.wiley.com/doi/pdf/10.1002/ajh.25232
https://www.nature.com/articles/s41375-018-0337-0
https://academic.oup.com/oncolo/article/29/1/e81/7240615

This research also led me to an insight into metabolic syndrome and inflammatory cytokines (IL-1, IL-6 and TFN-a) as a possible cause of CML and persistent LSCs.

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10071114/#:~:text=CML%20dev....
https://www.researchgate.net/publication/377781949_Cytokine_profile_in_p...
https://www.frontierspartnerships.org/articles/10.3389/or.2023.10573/full

This highlights the importance of low GI diet, periodic fasting and regular exercise.

I think it’s important to monitor for metabolic syndrome and insulin resistance by regularly checking blood glucose, insulin and lipids, especially for those on Nilotinib.

It seems that more serious side effects of Asciminib are expected at 200-400 mg pd which is used for T315I mutation, while the standard dose for cp is 80 mg pd.

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7724923/

Major side effects were asymptomatic elevations in the lipase or amylase level, rash, and constitutional symptoms (e.g., fatigue, nausea, headache, and arthralgia), most of which were of grade 1 or 2 and appeared to be equivalent in patients receiving asciminib twice daily and in those receiving the drug once daily. A maximum tolerated dose was not reached. Clinical pancreatitis was noted in 3% of patients overall, only at asciminib doses of more than 40 mg twice daily, and was manageable with dose modifications. Myelosuppression was uncommon and mostly of grade 1 and 2.

It is now recommended over Bosutinib for both efficacy and safety.

https://youtu.be/AU6F1GZYzp4?si=wl1KHWMVKNUHJWlp

https://www.scemblix-hcp.com/ph-cml/safety-profile

Safety and efficacy of combinations.

https://youtu.be/M2QCvpGAdGw?si=LkHbFMUb7acRvzZa

Potential for higer sucess rate of TFR

https://youtu.be/60n1qkajKxQ?si=aPE0cWFOrio399uu

https://youtu.be/BBcCCo2aw_o?si=KrxuDWJW7U4ptBqc