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Reply: Should I stop or change TKI therapy given the current Coronavirus outbreak?

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  • Carolina Pavlovsky
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8 months 5 days ago
Should I stop or change TKI therapy given the current Coronavirus outbreak?

In this young patient under dasatinib treatment and in MMR after 2 years, I would not consider dose reduction . We dont have scientific support to conclude that by reducing the dose , we will lower infections inmediately .
On the other hand, dose reduction on this patient could lead to a loss of molecular response adding another problem , not ideal at this time.
I would not recommend to reduce dasatinib dose nor TKI change.


ORIGINAL CASE:
One of my CML patients is a 30 year old health worker who was diagnosed 2 years ago in chronic phase, with a low ELTS score. 3 monthly BCR-ABL so far: 68% (diagnosis), 0.6%, 0.07%, 0.045%, 0.028%, 0.018%, 0.024%, 0.021%. Normal FBC otherwise – no cytopenia. No other medical diagnoses.

Give his workplace, he is very concerned about his risk of getting a COVID-19 infection and his risk of getting very sick with it. He has asked me if it would be worthwhile switching from Dasatinib 100mg to Imatinib 400mg in light of some suggestion that dasatinib is more immunosuppressive than imatinib. Alternatively, he asked if he should reduce his dasatinib dose to 70 or 50mg in light of the MDACC study with lower dose.

What would you advise him to do? Would your advice be different if he was 75 years old in the same clinical setting?

  • Andreas Hochhaus
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8 months 1 week ago
Should I stop or change TKI therapy given the current Coronavirus outbreak?

I am rather reluctant to advice CML specific measures based on CORONA, since data is rare.
A young man with perfect response to Sprycel should definitely continue full dose dasatinib until the trigger for discontinuation is reached.
There is no data the theoretical T cell inhibition will enhance the severeness of the CORONA infection.
In case of a 70 year old without a strong wish towards TFR and high risk of severe CORONA infection, I would switch do full dose imatinib.

  • David Ross
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8 months 1 week ago
Should I stop or change TKI therapy given the current Coronavirus outbreak?

I wouldn't change. Although the risk of infection is increased it is uncommon to see opportunistic infection with dasatinib. If he is young and otherwise fit the excess risk is likely small. On the other hand, his CML response is good, but not outstanding, so this also argues against de-escalation of therapy. Of course, nilotinib is probably less immunosuppressive than dasatinib, but retains potency. I would feel more positive about a switch to nilotinib, but I still wouldn't recommend it.

  • Michael Mauro
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8 months 1 week ago
Should I stop or change TKI therapy given the current Coronavirus outbreak?

My thoughts so far have been along the lines that we do not see significant incidence of opportunistic/viral/other infections with dasatinib (or any TKI for that matter) and consider a patient in remission to not be immune compromised per se. This would align imatinib and dasatinib and dissuade us from such a thought or change in therapy.

On the other hand, in trying to learn about prior pandemics and viral infections to manage the current issue of COVID, I understand that in some instances exaggerated immune/inflammatory response to such a virus can be more dangerous than older age/comorbid situations. I believe this was the case with the ‘spanish influenza’ later in the pandemic, where either a second wave/altered virus/re-exposure led to more effect on younger healthy people (essentially succumbing to severe inflammatory reaction/syndrome). I have a subtle concern that dasatinib could contribute to such a reaction- given its lymphocyte activation, NK effect, and the rare patient we see with inflammatory side effects (colitis, fevers, lymphadenopathy).

On the whole I would stay put and not change given the first thoughts; we have similar pathogens all around us, such as influenza, and we don’t see issues in CML patients differentially with different agents, etc. The second point is speculative and may not be likely for the same reason, we don’t see exaggerated response to other pathogens that I know of….

  • Jeff Lipton
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8 months 1 week ago
Should I stop or change TKI therapy given the current Coronavirus outbreak?

Definitely would not switch at this time. The dasatinib/infection controversy is probably related to the MD Anderson original data and DASISION which had more infections, the most identified of which were actually bacterial. Increased risk to the recent viral infection is theoretical at best. I think though, that given his degree of response, the French OPTIM data as well as the MDA data, would suggest that he does not need more than 50-70mg at this time and I think his dose could be reduced. Not sure that this reduces the risk, but definitely reduces the other risks such as pleural effusions.

  • Jane Apperley
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8 months 1 week ago
Should I stop or change TKI therapy given the current Coronavirus outbreak?

I think he will be at the same level of risk as anyone else of that age. In general with that response I might be inclined to reduce his dasatinib to 50mg