(Version 3.0; last updated September 28, 2021)
Input from Michael Mauro, MD; Brian Druker, MD; Jerald Radich, MD; Jorge Cortes, MD; Tim H. Brümmendorf, MD; Guiseppe Saglio, MD, PhD; Timothy Hughes, MD, MBBS; and Delphine Rea, MD.
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Note: Please review ASH’s disclaimer regarding the use of the following information.
Are you changing your treatment recommendations for CML (newly diagnosed or otherwise)?
No; fortunately, the approach to chronic myeloid leukemia (CML) treatment does not need to change as a result of the COVID-19 pandemic. There is still no evidence that any of the currently available tyrosine kinase inhibitors (TKIs) pose a greater or lower risk of acquiring SARS-CoV-2 or a worse outcome. Continued research efforts to understand the impact of COVID-19 infection in those with CML have suggested that mainly non-CML factors such as age, socioeconomic status, and vaccination status affect outcome of COVID-19 illness, rather than CML or TKI therapy.
Monitoring for myelosuppression (most common during the initial weeks of therapy) with regular bloodwork should continue, to avoid severe neutropenia. 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. Comorbid health conditions could affect the severity of COVID-19 infection; managing these, along with identifying and treating any significant adverse events possible with TKI therapy, remain essential. Pulmonary adverse effects associated with some TKIs, such as pleural effusion and pulmonary arterial hypertension, most commonly observed with dasatinib, may complicate or add to morbidity from severe SARS-CoV-2 infection. 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 patients with CML should follow standard local, regional, and/or national guidelines put forth by proper health authorities.
How are you treating accelerated-phase and blast crisis CML? Can allogeneic transplant proceed?
Patients with accelerated-phase CML responding well to TKI therapy can continue with proper monitoring. Transformation to accelerated-phase disease while on therapy can be managed with an appropriate TKI and proper monitoring. Blast-phase CML can be treated with a TKI alone or in combination with other agents; older age and/or significant comorbidities need to be considered given the cumulative risk of these factors when combined with severe immunosuppression. TKIs alone or in combination with lower intensity strategies may be preferable in such instances. Allogeneic stem cell transplantation (SCT), where indicated, may proceed with appropriate surveillance for SARS-CoV-2 if conditions at the site where SCT is to be performed are conducive to a safe transplant (e.g., adequate isolation from COVID-19 wards, adequate staffing). 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.
Should patients with CML be monitored any differently?
The monitoring of response and treatment adverse effects for patients with CML should proceed as prior to the pandemic, according to local, national, or international guidelines. While health care resources have and may continue to be stressed, in order to preserve good outcomes, standards of care should continue. Patients with CML in remission on regular (typically every 3 months) PCR monitoring should continue this schedule. Occasional delays in monitoring when conditions are not appropriate for traveling or visiting a monitoring site can be considered. 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. For access and continuity, remote encounters, including telephone and telehealth platforms, may be integrated into the care of patients with CML. Initiation of treatment-free remission attempts may be pursued as long as regular required monitoring is easily and safely assured by both provider and patient.
In patients who have developed the SARS-CoV-2 infection, should their CML therapy be adjusted or stopped?
Patients with CML who are 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 that those with chronic phase CML on a TKI are at higher risk of contracting SARS-CoV-2 or of having a more severe form of the viral infection compared to the general population.
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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 cases of severe COVID-19, TKI interruption should be discussed on a case-by-case basis. Patients with cardiopulmonary toxicity due to TKI who develop SARS-CoV-2 infection should stop the 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 coadministration, 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 or dasatinib). There are no known drug interactions or metabolism/drug transport effects if remdesivir is co-administered with TKIs.
Are there concerns or special considerations for patients with CML regarding SARS-CoV-2 vaccinations? What about a “booster dose” for those with CML?
Patients with CML continue to be considered appropriate to receive vaccines against COVID-19. While rare special circumstances may exist, all groups of CML patients — those early in treatment, in ongoing response, in deep remission, or off therapy having pursued treatment free remission — are appropriate and should pursue vaccination when available to them if not done already. Emerging data have demonstrated no excess adverse effects from the various vaccine strategies, including the novel mRNA vaccines from Pfizer-BioNTech and Moderna, the adenovirus-based vaccine from John & Johnson/Janssen, or the Oxford/AstraZeneca vaccine. 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.
To date, available data indicate good response to vaccination (generation of anti-SARS-CoV-2 spike antibodies in the case of two doses of mRNA vaccination) in patients with CML. In light of active potential integration of “booster” vaccine doses (e.g., a third dose of mRNA vaccine), patients with CML should proceed if and when available according to general population or age-based recommendations from health authorities and access for additional vaccination. Given the consensus and data that CML and TKI-based treatment present little impact on the immune system, despite being blood cancer patients on therapy, immediate or earlier additional vaccine doses after initial series or dose may not be as urgently needed. Rare circumstances and comorbidities, evidence of low or absent vaccine-derived antibody levels, and patient preference may drive early additional vaccination and discussion with the health care team is essential to guide next steps.
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