I came across the term hormesis which is, in summary, a conceptual depiction of the duality between low dose stimulation versus high dose inhibition. Interestingly, at the conceptual level, hormesis is a fit to some of the questions regarding TKI, and dose-response.
The following link nicely describes what hormesis is:
https://www.psychologytoday.com/intl/blog/the-gravity-weight/201903/the-...
The analogy I thought of is that of a gym-goer trying to lift heavy-weights. If the spotter (A person that helps you with a particular exercise) helps too much the lifter will have a weak stimulus to build strength but if the spotter helps just enough the lifter will have a bigger stimulus and will build more strength over time. No help = no lifting.
Lifter = Immune system
Spotter = Imatinib, Dasatinib, etc.
With this analogy in mind here are some of the things that I thought of concerning CML and TKIs. These are no claims, they are more on the question side of things:
- Starting at a lower than recommended dose might be a good balance between disease inhibition and immune system stimulation as opposed to inhibition with a toxic effect on the immune system. Is this the case of Dasatinib starting dose of 100mg vs 50mg?
- Intermittent dose; intermittence between inhibition and stimulation doses; every other day doses.
- Gradual dose reduction seems more appropriate than big jumps in a reduction. Destiny Trial?
- High doses seem necessary even at the cost of toxic side effects to bring back balance (cytogenetic response or molecular response).
- High doses have their purpose. Imatinib 600mg?
This is not a cherry-picked concept to justify an increase or reduction of TKI dose, I like to see it as a way to interpret, at a high level, some of the CML posts I read on CML forums because the low level mechanics of the disease is beyond my knowledge.