COVID-19 and CML: Frequently Asked Questions
(Version 2.0; last updated January 4, 2021)
Input from Drs. Michael Mauro, Brian Druker, Jerald Radich, Jorge Cortes, Tim H. Brümmendorf, Guiseppe Saglio, Timothy Hughes, and Delphine Rea
Note: Please review ASH's disclaimer regarding the use of the following information.
Are you changing your treatment recommendations for newly diagnosed CML?
No; newly diagnosed CML treatment, including diagnostic evaluation and choice of therapy, does not need to change. Myelosuppression may occur during the initial weeks of therapy, and regular bloodwork (typically every 1-2 weeks) is recommended as prior standard. The general principle to avoid severe neutropenia whenever possible to minimize the risk of infection continues to be best practice and dose interruptions (and if absolutely necessary, dose reductions) may thus be required in some patients.
There is no evidence that any of the tyrosine kinase inhibitors (TKI) currently approved for first line therapy pose a greater or lower risk of acquisition of SARS-CoV-2 or worse outcome.
Should therapy be changed for CML patients already on treatment?
Treatment should not be changed for patients who are asymptomatic and do not have documented infection with SARS-CoV-2. Our experience with TKIs used to treat CML to date has not revealed substantive evidence of immune suppression, increased risk of viral infection, or other effects which would increase risk from SARS-CoV-2. There are pulmonary side effects associated with some TKIs, such as pleural effusion and pulmonary arterial hypertension, most commonly with dasatinib, which in theory might complicate or add to morbidity from severe SARS-CoV-2 infection. These adverse events should be managed as per standard practice. Patients with such adverse events who develop symptoms consistent with SARS-CoV-2 and/or test positive for the infection should consider stopping therapy to decrease additional lung stress during infection and recovery. Monitoring and surveillance for SARS-CoV-2 for CML patients should follow standard local/regional/national guidelines put forth by proper health authorities.
How are you treating accelerated phase and blast crisis CML?
Patients with accelerated phase CML responding well to TKI therapy can continue with proper monitoring. Transformation to accelerated phase while on therapy can be managed with an appropriate TKI and proper monitoring. Blast phase CML can be treated with TKI alone or in combination with other agents; local conditions may warrant more caution for those with higher risk of SARS-CoV-2 infection and complications (older age and/or significant co-morbidities) making it more advisable to use a TKI as a single agent to avoid risk of severe immunosuppression. Advanced phase disease management needs to account for feasibility of safe monitoring and support (transfusion, management of possible infections, etc.) based on local/regional conditions. Allogeneic stem cell transplant, where indicated, should proceed with appropriate surveillance for SARS-CoV-2. Continued thorough evaluation of risk/benefit and assessment of the patient’s goals remains crucial for decision-making, planning and implementing the most appropriate therapy for each patient, including transplantation.
How should patients be monitored? Any modifications reasonable?
CML patients in remission on regular (typically every 3 month) PCR monitoring should continue this schedule. If local conditions warrant, remote testing (sample kit sent to patient or local provider, drawn, and returned by courier) should remain an option where possible to minimize patient travel and exposure. As a general principle, guideline-based monitoring, including specific timing for cases of ‘treatment free remission’ (TKI stopped) where more frequent monitoring is required, should continue normally. If conditions change, local/regional health care system capacity is limited or concern remains over higher risk for SARS-CoV-2 exposure or complications, less frequent monitoring can be considered on a case-by-case basis. Initiation of treatment free remission attempts may be pursued as long as regular required monitoring is easily and safely assured by both practitioner and patient.
In patients who have developed the SARS-CoV-2 infection, should their CML therapy be adjusted or stopped?
CML patients in treatment free remission (stable deep molecular response while off TKIs) who become infected should be managed the same way as the general population. At present, we have no evidence to suggest chronic phase CML patients on TKI are at higher risk of contracting SARS-CoV-2 or having a more severe form of the viral infection compared to the general population.
In the presence of non-severe confirmed SARS-CoV-2 or symptoms compatible with non-severe SARS-CoV-2, interruption of TKI treatment is not necessary. In case of severe COVID-19, TKI interruption should be discussed on a case-to case basis. Patients with cardiopulmonary toxicity due to TKI who develop SARS-CoV-2 infection should stop TKI until both the infection and the adverse events are resolved.
Is there any interaction between CML treatments and therapies being tried for SARS-CoV-2?
Available treatments for SARS-CoV-2 including convalescent plasma, corticosteroids, and the antiviral agent remdesivir may be used in patients with CML. Other options under investigation ideally should only be administered as part of a proper clinical trial. Given that a variety of supportive care as well as potential SARS-CoV-2 infection directed therapies may be given in conjunction with ongoing TKI treatment, review and discussion of known or possible drug-drug interactions with oncology pharmacy staff is recommended whenever possible. Attention should be paid to impact on concomitant medication or TKI metabolism with co-administration, as well as potential need for increased EKG monitoring and normalization of electrolyte imbalances (particularly K+ and Mg+), especially with ongoing TKI therapy associated with QT interval effects (e.g. nilotinib). There are no known drug interactions or metabolism/drug transport effects if remdesivir is co-administered with TKIs.
Am I eligible to and should I receive vaccination against COVID-19?
At this time, based on best available information, patients with chronic myeloid leukemia (CML) are considered appropriate to receive vaccines against COVID-19. While rare special circumstances may exist, most patients, whether early in treatment, in ongoing response, in deep remission, or off therapy having pursued ‘treatment free remission’ are likely appropriate and should pursue vaccination when available to them. In general, neither excess risk of adverse effects or concern over effectiveness are expected for CML patients. Different vaccine strategies, including the novel mRNA vaccines from Pfizer-BioNTech and Moderna, along with the Oxford/AstraZeneca vaccine, appear safe and effective and no preference is noted at this time. Since other health conditions and individual medical histories (including reactions to prior vaccinations) may affect advice, suitability, and timing, discussion with a patient's entire health care team is recommended prior to vaccination.