This 52 year old woman has had basically never achieved a sustained BCR-ABL <1% in the last 4.5 years, regardless of the treatment she’s been given, even at the high dasatinib dose of 140mg daily for over 1 year. No kinase domain mutation had been found, and I assume additional cytogenetic abnormalities had been sought and discounted. Compliance should be ensured and pharmacological interactions excluded (140mg dasatinib for 1yr+ in a 52 year old woman without side effects at full compliance…? Only 50-60% chance of that happening I would have thought…) Can you measure drug levels? Low level mutants may be present, of course, but if they are still at levels below that detectable by Sanger, they are probably not responsible for the intrinsic TKI resistance.
Options:
1. Bosutinib – very little chance of improving response
2. Ponatinib – PACE data showed CCyR of 48% at 2 years for patients resistant or intolerant to 2 other TKIs. It may be that the majority of responders in this study were intolerant patients Cost and long term toxicity are both prohibitive
3. add in interferon – worth a try if can be sourced
4. Enrol to the Phase I combination trial of dasatinib plus the Anti-PD-1 antibody – if it is available locally.
5. Wait for the trial of ABL001 combination with nilotinib to be available (Or ABL001 alone – not sure how active it would be in this case…)
6. Transplant – should be considered, but difficult to commit to in 2015. Would be less reluctant if she was younger and a sib donor was available.
7. Do nothing. Probably not as horrible as it sounds if the IRIS data is applicable, compared to TRM. The IRIS landmark data would suggest that even though this is a high risk situation, patients with BCR-ABL between 1-10% at 18 months could still be expected to have a transformation free survival of ~80%. This data may be not applicable to this case in entirety: Landmark analyses are not available for later time-points. Nor do we know the number of patients potentially rescued from AP/BC by a therapy other than imatinib, though this is likely to be small.
In the absence of Anti-PD-1, I would edge towards a transplant, followed a close second by do nothing and waiting for the ABL001 phase II.