CML, TKI treatment and COVID-19 disease

Dr Delphine Rea, Saint-Louis University Hospital, Paris, France and Professor Rudiger Hehlmann, ELN/EHA-SWG for CML

Neither chronic phase CML nor BCR-ABL tyrosine kinase inhibitors (TKI) induce a state of clinically significant immune suppression and there are no data suggesting that chronic phase CML patients may be at higher risk of infection by the novel Coronavirus than the general population.

What to do in newly diagnosed CML?

In newly diagnosed CML, delayed introduction of TKI therapy is not recommended, as:

1. Uncontrolled leukocytosis might worsen lung damage / gas exchanges in case of severe COVID-19 disease
2. Delayed introduction of TKI may increase the risk of CML progression to advanced-phases

However, extreme caution is advised during the first 3 months of TKI treatment as severe cytopenia may occur, thus increasing the risk of severe COVID-19 disease. Systematic test for infection at the time of CML diagnosis in the absence of symptoms may be ideal but should be discussed on a case-to case basis, depending on test availabilities, center/country policy.

What to do in TKI-treated CML patients?

Prophylactic interruption of TKI is not recommended as it may lead to loss of response and CML relapse/progression, especially if access to regular monitoring of CBC counts and BCR-ABL transcripts is altered by the epidemic context. In patients facing resistance or intolerance to current TKI, it is not recommended to delay a change in therapy as outcome may be jeopardized.

What to do in CML patients in TFR?

CML patients who discontinued TKI therapy for less than 6 to 12 months and who do not have access to regular monitoring of CBC counts and BCR-ABL transcripts in an altered epidemic context are advised to rapidly discuss with their oncologist/hematologist the possibility to restart TKI treatment and postpone TKI discontinuation at the end of the novel Coronavirus epidemy. For the same reasons, TFR attempts during the epidemic phase should be postponed.

What to do in case of CML and symptoms compatible with COVID-19 disease?

Patients in TFR should be managed the same way as the general population. At present, we cannot assume that chronic phase CML patients on TKI are at higher risk of severe forms of the viral disease than the general population. Exceptions to this last statement may reside in:

1. Onset of severe cytopenia on TKI therapy during the early stages of treatment (see above)
2. Active TKI-induced hypersensitivity pneumonitis or other forms of iatrogenic lung damage

In the presence of non-severe confirmed COVID-19 or symptoms compatible with non-severe COVID-19, systematic interruption of TKI treatment is not recommended. In case of severe COVID-19, TKI interruption should be discussed on a case-to case basis. Of note, we do not know whether duration of viral shedding in TKI-treated CML patients differs from that seen in the general population.

Warning box: All TKI have the capacity to prolong the QTc interval and strongly interact with drugs such as chloroquine and azithromycin, 2 drugs that are currently evaluated against COVID-19. Combining these medications with TKI in the absence of medical prescription and supervision may lead to fatal torsade de pointe.