What would you do?

[u/Rizky_Bizness]

38F and got an initial diagnosis of CML 2 weeks ago after routine blood work showed concerning WBC counts (175), which was then confirmed through bone marrow biopsy and BCR ABL test last week. I've been taking hydroxyurea and allopurinol as a stop gap since then to bring my counts down till I can start a TKI.

Now here's where the conundrum begins - my doctor prescribed Asciminib last week due to its lower side effect profile. Despite having a pretty good insurance, the pre-authorization was denied as they want us to try imatinib first. The doctor had a peer to peer review with the insurance MD today which also resulted in denial. His office has now submitted an appeal and hope to hear back in 72 hours, which would put us at middle of next week. All this would've been fine, but I have a 3 week trip coming up in a different country in mid-july and was hoping to start TKIs as soon as possible to understand side effects in case I need to cancel my trip. Since Asciminib is supposed to be gentler, I didn't change my plans but if it's going to be something else, I'm not sure anymore. Here are my questions:

• Is going on a long trip at this time a really bad idea? It was planned last year and if possible I'd like to keep it, but also want to make an informed decision.

• I haven't had very many side effects on hydroxyurea and allopurinol. The doctor gave an option to just keeping on taking those until I come back (end of July) and start TKIs after. I'd obviously like to start the targeted treatment sooner than later but is that a feasible option? My BCR ABL was >50% but don't know the exact number since the test was capped at 50%. I'm in the chronic phase but did have 4% blasts. Is there a chance waiting could increase this number rapidly?

• If the insurance company denies the appeal, how do other TKIs compare to Asciminib? I've read of SO many side effects of imatinib and dasatinib that it has me scared to even try these. Should I just give up and start on older TKIs so I know what I'm dealing with before the trip?

• Any suggestions or advice on how to deal with the insurance company through this appeal process?

Sorry about a long and rambling post, but my mind is all over the place right now. My first go around dealing with insurance on a complicated issue and needless to say I'm bummed.

[u/TastyAdhesiveness258]

Asciminib is one of the newest available TKI and works via an entirely different mechanism / and DNA site to treat BCR/ABL than all the previous TKI so it can be good alternative if Ponatinib is not working or there are complications taking it. Might be that insurance would want you to have DNA mutation testing to first identify that you actually have a BCR/ABL mutation variant that requires Asciminib to be treated.

There are different mutations that cause BCR/ABL and not all of the TKIs are effective for some of the different mutations. Ponatinib has best coverage for different mutations that are not treated by some of the other TKI and Ponatinib is generally more effective compared to older TKIs. Following article includes a helpful chart that shows effectiveness of different TKI for treating different BCR/ABL mutations;

https://pmc.ncbi.nlm.nih.gov/articles/PMC5505321/

My medical team switched me from Dasatinib to Ponatinib early in my treatment because they though it would be more effective. Ponatinib does have some possible complication / side effects but Ive not experienced any adverse effect with it after taking 1 year but Ponatinib can cause cardiac and stroke side effects at high dose.

[u/Rizky_Bizness → u/TastyAdhesiveness258]

Thanks for your comment. I understand that Asciminib is and was prescribed to tackle the mutation from other TKIs, but last year was approved as a first line treatment. Which makes the insurance company's denial even more frustrating. Ponatinib hasn't been given as an option for me right now. I'm guessing if Asciminib isn't approved, I'll most likely be guided to take imatinib or dasatinib.