Advice regarding COVID -19 for Australian WM patients is provided below by three WM specialists at three major WM Cancer Centres in conjunction with world-wide WM resources. Issues addressed in the advice are:
- What is COVID-19?
- I have been diagnosed with WM; am I in the high risk or vulnerable group?
- I have WM but have never been treated: am I still in the vulnerable group?
- I have WM and have been treated previously: what is my risk?
- I have WM and am receiving treatment now: what should I do?
- I have been informed that I need to start treatment for the first time: will that change?
- Is my treatment likely to be changed?
- I have already started treatment: will anything change?
- I have early signs of relapse: how is that likely to be managed?
- I am enrolled in a clinical trial: what should I do?
- Will there be an impact on supportive treatments for WM?
- Immunoglobulin infusions (IVIG)
- Is testing to establish if I have COVID-19 (serological testing) likely to be affected by clonal IgM in patients with WM?
- How can I minimise my visits to the hospital?
- What else do I need to know?
- I am worried that I have COVID-19: what should I do?
The WhiMSICAL Registry has been enhanced to include specific questions regarding the impact of COVID-19 on WM patients as detailed at http://www.wmozzies.com.au/index.php/news-and-events/news/
What is COVID-19?
Coronaviruses are a group of viruses that can affect humans and animals. Some members of the coronavirus family cause mild illnesses, such as the common cold and gastrointestinal infections, whereas other members of the same family can cause severe illness, such as SARS (Severe Acute Respiratory Syndrome) and MERS (Middle East Respiratory Syndrome).
There is currently an outbreak of a disease caused by a new strain of coronavirus that is called the SARS-CoV-2-associated coronavirus disease 2019 (COVID-19). COVID-19 causes a spectrum of illness, from mild to very severe, similar to SARS and MERS. The outbreak started in a province of China and has spread to many other countries outside of China. The virus can be spread from person to person, so good hygiene is very important in slowing the spread of infection.
Resources provided by the ACT Government are provided here:
. These are regularly updated.
Answers to frequently asked questions can be found here: https://www.covid19.act.gov.au/faqs
There are currently no treatments or vaccines for COVID-19.
I have been diagnosed with WM; am I in the high risk or vulnerable group?
At present, the following patients are classified as vulnerable:
- at least 70 years of age or
- already under treatment for chronic health conditions or are immune compromised are classified as vulnerable, or
- have been diagnosed with COVID-19 virus or
- have been required to isolate themselves in quarantine; or
- the person meets the current national triage protocol criteria for suspected COVID-19 infection
People at any age with significant immunosuppression are defined as those with:
- Haematologic neoplasms: leukemias, lymphomas, myelodysplastic syndromes
- Post-transplant: solid organ (on immunosuppressive therapy), haematopoietic stem cell transplant (within 24 months or on treatment for GVHD)
- Immunocompromised due to primary or acquired immunodeficiency (including HIV infection)
- Current chemotherapy or radiotherapy
- High-dose corticosteroids (≥20 mg of prednisone per day, or equivalent) for ≥14 days
- All biologics and most disease-modifying anti-rheumatic drugs (DMARDs) as defined as follows:
- Azathioprine >3.0 mg/kg/day
- 6-Mercaptopurine >1.5 mg/kg/day
- Methotrexate >0.4 mg/kg/week
- Prednisone >20 mg/day. If <14 days treatment, can resume work when treatment ceased
- Tacrolimus (any dose)
- Cyclosporine (any dose)
- Cyclophosphamide (any dose)
- Mycophenolate (any dose)
- Combination (multiple) DMARDs irrespective of dose
All patients with WM are therefore classified as vulnerable.
I have WM but have never been treated: am I still in the vulnerable group?
WM is an indolent (slow or chronic) lymphoma with distinct features and treatment options.
Just having the disease may
increase the risk of lowering immunity, because people with WM often produce fewer antibodies than normal. This may not be significant under normal circumstances but in this time of COVID-19, we are assuming that everyone in the so-called ‘Watch and Wait’ category is potentially at risk.
This is why people at any stage of their disease are included in the vulnerable category.
I have WM and have been treated previously: what is my risk?
Many treatments used in WM do lower the immune system but it is not known how long this effect persists or how they may affect the body's response to COVID-19.
- This is because testing of the immune system in routine practice is not feasible and not required in most cases
- During chemotherapy treatment, the white blood count (the neutrophils) are closely monitored; this usually recovers well once chemotherapy is finished and is no longer a significant factor
- Newer agents / targeted therapies like ibrutinib may affect the immune system in a different way to chemotherapy (for example bendamustine or DRC) and monoclonal antibodies such as rituximab. How ibrutinib and similar treatments affect the body’s response to COVID-19 is not yet fully known.
Doctors make certain assumptions based on how patients in this group are affected by other more familiar viral infections.
- Illnesses such as influenza (for which vulnerable persons are offered the annual flu vaccine)
- Herpes viruses that cause illnesses such as chicken pox and shingles (varicella zoster) or cold sores (herpes simplex) for which tablets like acyclovir and valaciclovir can be used for prevention and treatment
- Under normal circumstances, a pragmatic approach is made regarding the use of preventative measures such as anti-viral meds (valacyclovir). Patients are thought to be at highest risk in the first three months after completion of therapy. This risk diminishes in the following six to twelve months
- Note that acyclovir and valaciclovir does not have activity against COVID-19
I have WM and am receiving treatment now: what should I do?
- None of this is an exact science and varies from person to person, so in the current crisis, until we know more, people at any stage of their disease are included in the vulnerable category.
Please do not stop any treatment for your WM without discussing this with your doctor, or a member of their team.
People at any stage of their disease are included in the vulnerable category.
Different combinations (such as bendamustine, DRC and fludarabine) and different strengths of treatments (such as chemotherapy given for a stem cell transplant) suppress the immune system to varying extents and for different durations.
Those on active treatment may see a change in their treatment plan so as to minimise their immune suppression, preferably without adversely affecting the outcome that is intended from using the WM treatment in the first place.
I have been informed that I need to start treatment for the first time: will that change?
The point at which treatment is commenced will be delayed if possible; watchful waiting is the preferred strategy whenever possible.
- Treatment will be given in symptomatic patients, but if the symptoms are mild and / or tolerable, treatment is likely to be deferred, alongside close monitoring
- For patients presenting with anaemia (low haemoglobin) as a main problem (resulting in symptomatic fatigue), intravenous iron infusions could be considered. This requires one- or two-day case visits to the hospital but if this results in a rise in the haemoglobin, the need for chemotherapy could be deferred for a number of months until the coronavirus precautions are lifted
Is my treatment likely to be changed?
- If your plasma viscosity is a main concern, plasma exchange may be commenced to remove excessive IgM from the blood and ‘thin’ the blood as a holding measure until chemotherapy starts. This would entail a visit every two to four weeks to a centre that can carry out the procedure. Plasma exchange does not itself suppress the immune system.
- Less immunosuppressive chemotherapy treatments (for example cyclophosphamide instead of bendamustine) may be chosen or the number of intended cycles may be reduced or deferred to limit visits to the hospital
- Oral chemotherapy options may be given instead of intravenous options to facilitate self-isolation
- Rituximab maintenance is not recommended because of lack of evidence of benefit, and to limit the burden of travelling to healthcare centres and the risk of immunosuppression
I have already started treatment: will anything change?
- It is not known whether these changes would affect the eventual outcome of treating the disease. However, there is widespread agreement that it is crucial to keep vulnerable people isolated as far as possible at this stage. Once regulations about this change, treatment choices will be revisited by the treating team.
In the absence of evidence to guide us, treatment decisions should be based on your general health, any other illnesses, and the response already achieved so far, and balancing this against the risk of developing COVID-19 infection.
- It is thought that persons on BTK inhibitors (ibrutinib, acalabrutinib and zanubrutinib) should be continued on treatment. Stopping treatment has a high risk of causing IgM flare, increasing risk of symptoms such as fever and respiratory symptoms (which can be confused as COVID-19 related) and high blood viscosity, which may trigger the need for plasma exchange
- For patients who have already achieved a good response to rituximab-chemotherapy, a reduced number of cycles may be considered. Alternatively, a switch to less immunosuppressive treatment may be considered
- Maintenance rituximab should not be given because of the lack of evidence, increased risk of immunosuppression, and of the requirement for travel to the hospital
I have early signs of relapse: how is that likely to be managed?
- Ultimately, in order to err on the side of safety, we need to balance risks versus benefits.
When possible, commencement of treatment will be delayed if mild, tolerable symptoms are present with continuation of close monitoring.
- For patients presenting with anaemia (low haemoglobin) as a main problem (resulting in fatigue or shortness of breath), alternative ways of boosting haemoglobin such as erythropoietin injections in eligible patients e.g. those with chronic renal failure (can be taken at home) or intravenous or oral iron may be used as a holding measure. Intravenous iron given once or twice would need a visit to a hospital but if this results in a rise in the haemoglobin, further visits for chemotherapy could be put off altogether for a number of months
I am enrolled in a clinical trial: what should I do?
- Stem cell transplants are not taking place at present. If you were planned for one, an alternative holding measure may be considered.
The clinical trials team will seek advice from the sponsors who are running the trial about adapting the care of patients who are on clinical trials.
- supply of medication for longer durations to reduce patients having to come into the hospital
- postponement of visits to the hospital for trial-related tests such as bone marrow biopsies and scans
Will there be an impact on supportive treatments for WM?
- visits that are necessary on safety grounds, in order to continue receiving the trial medication (for example blood tests or ECGs - heart tracings to ensure it is safe to continue) may need to go ahead as planned but the possibility of more local provision may be possible.
Several supportive measures are being implemented to minimise risk and reduce the chance of hospital admission.
- Growth factor (G-CSF) injections are likely to be used in patients who are receiving chemotherapy to reduce the risk of neutropenia (low white cell count). The clinical team will decide how long and how often these injections may be needed. They are given subcutaneously (under the skin) and this can be done at home
- Some patients may receive preventative antibiotics if they are already experiencing recurrent infections
Immunoglobulin infusions (IVIG)
- Where indicated, routine vaccination against influenza and pneumococcus should be continued despite reports of impaired responses.
Some people are already receiving antibody replacement because they experience repeated infections. This is usually administered intravenously in hospital or subcutaneously.
- A decision is likely to be made on a case-by-case basis considering the balance of risk and benefit. Continuing to provide IVIG as a day case is preferred as it seems contrary to remove a protective measure at a time of pandemic
- If the risks of travelling to a hospital are considered too high, the clinical team may consider alternate measures
- Dependent on patient circumstances and hospital capacity, short-term antibiotics may be given instead (to replace immunoglobulin therapy)
- The dose of immunoglobulin may be changed to reduce interval between attendances
Is testing to establish if I have COVID-19 (serological testing) likely to be affected by clonal IgM in patients with WM?
- For suitable patients the use of subcutaneous immunoglobulin may be used. This will depend on the capacity of the centre to deliver a training package to patients to self-administer the treatment and receive deliveries at home.
Blood tests for COVID-19 are being developed to identify COVID-19 specific IgM antibodies to look for evidence of infection and will not be affected by the total IgM or paraprotein levels.
Such IgM antibodies are the ‘first responders’ to any infection that we encounter - they are produced as part of the early immune response and so can help to confirm whether we have been infected. This IgM is different to the IgM produced by WM cells
, and can still be picked up by the test despite the presence of WM-related IgM. While such testing is already in widespread use to detect a range of infections, a specific test for COVID-19 has needed to be developed in the past weeks.
One concern about this test in WM patients is that previous treatments such as rituximab (which targets B cells whose job it is to produce antibodies) might result in not being able to mount an immune response to COVID-19
, and there is a possibility of a negative serological test even if they were exposed to the virus (having the virus but with a negative test result).
How can I minimise my visits to the hospital?
All hospitals in Australia are working on and have implemented contingency measures so as to minimise the need for all patients, especially the vulnerable, to leave their home. These include:
- home delivery of oral medication where possible (exact arrangements vary between regions due to geographical and infrastructure differences)
- changing intravenous to oral treatments if possible
- dispensing longer periods of oral medications
- reducing the number of cycles to be given, especially if there is already evidence of good response
- considering treatment breaks or pauses while the risk of COVID-19 is particularly high
- using growth factor injections to reduce the chance of low blood counts and reduce admission rates
What else do I need to know?
- these measures are unprecedented and have been put in place specifically for this pandemic. It is not known if these changes will alter the eventual treatment outcome, but it makes sense to take these important safety steps now. Once the pandemic is under control, clinical teams will review the treatment strategy once more.
We currently are in an unusual time where there is little evidence on which to base decisions at a time where things are changing fast.
- Each day, observations around the world being made during this pandemic will be of immense help in the future
- Clinical trials to treat COVID-19 are well underway
- There is an unprecedented amount of collaboration going on between doctors and scientists across the globe to share information to make it safer to care for patients in this difficult time. The picture is changing on a daily basis
- All Australian hospitals and healthcare centres are working hard to put new practices in place in response to guidance that is coming from the Australian government
- WM patients and advocates play an important role in the dissemination of information
- WMozzies will regularly update the WM community with fact-checked information
- We would recommend speaking to your specialist team if you have any questions or worries about coronavirus and WM.
I am worried that I have COVID-19: what should I do?
- Please seek advice from your hospital/healthcare centre and GP or specialist regarding your specific risk as the situation may vary from centre to centre.
If you think you might have been exposed to the virus, or develop symptoms, you should follow the same instructions as those for the general public
. Do this as soon as you get symptoms.
- Please contact the COVID-19 helpline on 1800 020 080
- Please contact your GP and/or your specialist.
- If you are receiving chemotherapy treatment, phone your hospital team so they are aware.
- In an emergency, call Emergency if you are seriously ill.