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Expert Opinion from the NCRI CML Subgroup, updated 23rd March 2020

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The latest UK government updates are listed here:

https://www.nhs.uk/conditions/coronavirus-covid-19/  and https://www.gov.uk/government/publications/covid-19/guidance

According to the above links, you will be contacted (via letter) by the NHS by Sunday 29 March 2020. Please wait to be contacted.

Expert Opinion from the NCRI CML Subgroup 17th Mar 2020, updated 23rd March 2020

  • Please Note. Patients with CML will have received letters from their GP practice, stating that they are in the high-risk category. This will allow full access to government support services and patients are entitled to follow these recommendations. If patients have not received this notification by 29/03/20, they should contact their GP surgery and not their hospital.

For specific questions regarding your condition and treatment (outside of the NHS general guidance for high risk conditions) please contact your CNS or your CML specialist.

Are CML patients at higher risk for a more severe COVID-19 infection?

  • Patients with CML do not appear to be at a higher risk of getting COVID-19, although data are limited.
  • Having a diagnosis of CML or being treated with TKI therapy does not convincingly cause clinically significant immune suppression.
  • CML patients can be at a higher risk of COVID-19 infection if they are older (age over 70 years), have other medical conditions or are receiving other treatment which will suppress the immune system.
  • There are no published data on the course of the COVID-19 infection in CML patients treated with tyrosine kinase inhibitors (TKI) and reports are rare. Reassuringly, very few CML patients on TKI therapy were infected in the Hubei province in China, and the outcome was similar to the general population.
  • Self-isolation (self-quarantine) for 12 weeks is recommended for at-risk individuals, but in our specialist opinion, the diagnosis of CML or treatment for CML alone does not clearly fall in this category.
  • The life expectancy of CML patients is currently approaching that of the general population. The decision to place CML patients on TKI therapy in the high-risk category for COVID-19 infection must not have a negative impact on triage or other in-patient treatment related decisions, due to their excellent outcomes

Patients should not interrupt or reduce their TKI medication without the advice of their CML specialist team

NCRI CML Sub-group:

Dr Dragana Milojkovic (Chair); Prof Jane Apperley; Dr Jenny Byrne; Prof Richard Clark; Prof Mhairi Copland; Sandy Craine consumer representative; Prof Nick Cross; Dr Joanne Ewing; Prof Letizia Foroni; Dr Paolo Gallipoli; Dr Andrew Goringe; Prof Brian Huntly; Dr Hugues de Lavallade; Dr Andrew McGregor; Prof Adam Mead; Dr  Kate Rothwell; Prof Stephen O'Brien; Prof Oliver Ottman; Dr Seonaid Pye; Dr Anuparna Rao paediatric representative; Dr Graeme Smith; Richard Szydlo MSc,PhD; Dr Andres Virchis. Trainee members Dr Simone Claudiani; Dr Gillian Horne.

EHA: Recommendations for specific hematologic malignancies

https://ehaweb.org/covid-19/covid-19-recommendations/recommendations-for-specific-hematologic-malignancies/

CML, TKI treatment and COVID-19 disease
Dr Delphine Rea, Saint-Louis University Hospital, Paris, France and Prof Rudiger Hehlmann on behalf of 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.  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.