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

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Tim Hughes
Topic Author

4 years 1 month ago - 4 years 1 month ago #1751 by Tim Hughes

Should I stop or change TKI therapy given the current Coronavirus outbreak? was created by Tim Hughes

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?

Last edit: 4 years 1 month ago by Nicola.

Delphine Réa
Topic Author

4 years 1 month ago - 4 years 1 month ago #1752 by Delphine Réa

Replied by Delphine Réa on topic Should I stop or change TKI therapy given the current Coronavirus outbreak?

We have to admit that more infections were reported with dasatinib 100mg QD than with imatinib 400mg QD in the DASISION trial. On a daily basis, I indeed see that during fall/winter, some but not all full-dose dasatinib treated patients have more upper respiratory tract infecttions than others, thus I routinely recommend flu vaccine for them, on a yearly basis and in some pneumococcus vaccine. However, I don't see a need for preventively and systematically switching our patients from dasatinib to imatinib because of the coronavirus epidemy, in the absence of infection. What I find reasonable is the following:

1- continue TKI treatment as it is, if no problem.
2- In case of coronavirus infection, inform hematologist immediately. For those patients in optimal molecular response on dasatinib, I recommend dasatinib interruption and reintroduction upon cure of the viral infection. For those not in optimal response or before optimal response induction (at early stages of CML therapy) in which interrupting the TKI due to COVID would jeopardize CML, I would then switch to a different TKI (choice made on patient personal background and CML characteristics).

Delphine Réa

Last edit: 4 years 1 month ago by Nicola.

Jorge Cortes
Topic Author

4 years 1 month ago - 4 years 1 month ago #1753 by Jorge Cortes

Replied by Jorge Cortes on topic Should I stop or change TKI therapy given the current Coronavirus outbreak?

This is a difficult dilemma because we know little about coronavirus in general. However, my impression is that the immunosuppressive effect of dasatinib is modest at most. I am not advising my patients to come off therapy or do anything special other than take the common precautions that we are all being advised to take, namely avoid contact with anyone with symptoms (whether proven coronavirus or not), good hand wash (soap better than sanitizer, but the latter good if not able to use soap and water like when traveling), etc. A dose reduction could be considered, acknowledging that we do not know what effect a modest change in dose could have on the immune competency. I hope this helps.

Regarding the same scenario in a 75 year old CML patient:
I would just be more emphatic about the other precautions, particularly some sort of social isolation.

Last edit: 4 years 1 month ago by Nicola.

Giusseppe Saglio
Topic Author

4 years 1 month ago - 4 years 1 month ago #1754 by Giusseppe Saglio

Replied by Giusseppe Saglio on topic Should I stop or change TKI therapy given the current Coronavirus outbreak?

For this young patient, as he is in MR4, I would simply be very careful during this period to avoid contacts and to reduce at maximum the risk of contamination, but I would continue the same dosage of dasatinib as at the end of the day we do not know if 70 or 50 mg have a different effect with respect to 100mg on the immune response (that is also only supposed and not demonstrated).

Regarding the same scenario in a 75 year old CML patient:
Probably my advice would be different. 50 mg just to maintain this molecular response achieved should be enough and not only for the risk of COVID-19 infection, but also for the other possible toxicities. In general, we do not use dasatinib at this age, but imatinib. However as this hypothetical patient has tolerated well dasatinib so far, I would not see the need to change the therapy, but I would reduce the dose.

Last edit: 4 years 1 month ago by Nicola.

Gianantonio Rosti
Topic Author

4 years 1 month ago - 4 years 1 month ago #1755 by Gianantonio Rosti

Replied by Gianantonio Rosti on topic Should I stop or change TKI therapy given the current Coronavirus outbreak?

I'm answering based on my experience with dasatinib, 2 cases where there was NO reason to expect a severe infection, no reason and both died of a septic shock. Due "to dasatinib"? Unclear but suspected at least. SO, I would say yes, switching to imatinib would be appropriate.

Last edit: 4 years 1 month ago by Nicola.

Jane Apperley
Topic Author

4 years 1 month ago - 4 years 1 month ago #1756 by Jane Apperley

Replied by Jane Apperley on topic 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

Last edit: 4 years 1 month ago by Nicola.

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Registered Address: International CML Foundation - 20 Eversley Road - Bexhill-On-Sea, East Sussex, TN40 1HE - UK