Our patient is a case 37 year old male with CML-CP who was initially on Nilotinib for 6 months and progressed to Myeloid Blast crisis. He was then induced with Ponatinib and Azacytidine following which he underwent Matched sibling donor transplant on 01/07/2020 from his brother as the donor.

Post transplant he had full donor chimerism (100%) and his BCR-ABL1 was 0.0895% at Day +28. He was started on Ponatinib maintenance 15mg/day and his BCR-ABL1 at Day 100 was 0%. By Day +60 his BCR-ABL1 copies rose to 8.5% for which a Kinase domain mutation analysis showed Y253H mutation. Ponatinib was continued after increasing the dose to 45mg/day. He was also started on Azacytidine maintenance for 12 cycles. As the BCR-ABL1 was persistent ast 0.0730% ponatinib was swtitched to dasatinib 140mg as per the kinase domain mutation and underwent 4 sessions of DLI from donor following which his BCR-ABL1 has be 0% at each analysis till 15/11/22.

  From 27/2/23 BCR-ABL1 copies have been fluctuating and the readings are
   7/2/23- 11.43%
   07/3/23-0.53%
  21/03/23-1.17%
   11/4/23-6.76%
    02/5/23-0.0258%
During the above period dasatinib was stopped and ponatinib was restarted and kinase domain mutation showed Y253H mutation sensitive to dasatinib and bosutinib. Azacytidine too was restarted at this time.
We shifted the patient to bosutinib 500mg now from 02/5/23 and we have continued the azacytidine and his BCR-ABL1 reports have been
11/7/23-0.0347%
31/7/23-0.0667%
4/9/23-0.1169%
28/9/23-0.0979%
9/11/23-0.0081%
9/1/24-0.0779%
8/2/23-0.2633% At this point the bosutinib was stopped and he was shifted to ponatinib 45mg and asciminib, also we treated the patient with decitabine and venetoclax
Kinase domain mutation shows Y253H and E255K/V mutation

Now his BCR-ABL1 reports are

16/3/24-0.0646%
16/4/24-0.0519%
11/6/24-2.1113%


Now that he is losing his response, how do we proceed from this point?

 

This is a very difficult case. The patient looks to have exhausted all available TKI options.

I would wish to ensure the patient has good compliance with therapy at all times.

Is there the option of one of the newer TKIs (e.g. olverembatinib, vodobatinib, TERN-701) via a clinical trial or compassionate use programme?

Is there an option for further DLI or potentially a second alloSCT from a different donor?

Thank you for your email. The patient has unfortunately progressed to myeloid blast crisis again. We are reinducing him with dasatinib and FLAGida as his Kinase domain mutation shows the Y253H mutation.

How can we get access to other TKIs?

I will propose asciminib definitely which is really well tolerated