COVID-19 (coronavirus) and myeloma and AL amyloidosis treatment

Myeloma Patients Europe (MPE) has received a range of queries from members, myeloma patients and AL amyloidosis patients about the impact that the COVID-19 (coronavirus) situation will have on treatment and care.

To answer these questions and to understand the impact in different European countries, MPE has been speaking to experts and reviewing national treatment guidance. Below is a Question and Answer (Q&A) on how treatment, hospital appointments and clinical trials may be affected for patients.

If you have any further questions or comments, please email info@mpeurope.org.

Note: it is very important that patients speak to their doctor, nurse or healthcare team to discuss specific questions relevant to their treatment and care. Patients should continue attending hospital appointments and taking their treatment as normal, unless instructed otherwise by their doctor, nurse or healthcare team.

TREATMENT

Will the treatment of myeloma and AL amyloidosis patients be affected during the COVID-19 outbreak?

Myeloma and AL amyloidosis patients should be prepared for changes to their treatment during the COVID-19 outbreak.

Patients are at a higher risk from COVID-19 because myeloma and AL amyloidosis, and their treatments, weaken the ability of the immune system to fight infection. For this reason, the advice is for myeloma and AL amyloidosis patients to stay at home to reduce the likelihood of catching COVID-19.

Doctors will balance the risks and benefits of patients attending hospital appointments to receive their treatment. In collaboration with patients, they will assess whether any treatment changes can be made to reduce the number of hospital visits.

Patients should speak to their doctor, nurse or healthcare team about whether their treatment will be affected during this time.

How will the treatment of myeloma and AL amyloidosis patients be affected?

Advice that patients receive about treatment changes will vary and depend on individual circumstances. Advice may also depend on the circumstances within a specific country, such as the number of COVID-19 patients, capacity of intensive care units, the availability of alternative treatments and national guidance.

For some patients their treatment will continue as normal. However, other patients may be recommended treatment changes such as:

• Reducing the frequency of administration, where the evidence supports this (i.e. receiving a treatment less often).
• Switching to an oral based treatment regimen (e.g. tablets to be taken at home).
• Receiving subcutaneous injections of treatment at home, where facilitated by the health system.
• Deferring procedures such as autologous stem cell transplantation to a future date, where clinically appropriate to do so.
• Amending or deferring participation in a clinical trial.
• Reducing the dose of certain treatments (e.g. reducing the dose of steroids to prevent a further weakening of the immune system).
• Stopping treatment altogether, where clinically appropriate to do so (e.g. where a patient is in good remission).

Any treatment changes should be made in discussion between a patient, their doctor and healthcare team. Decisions will be based on clinical evidence and on clinical judgement.

Patients should speak directly to their doctor, nurse or healthcare team if they have any questions or concerns about treatment changes during this time.

How will autologous stem cell transplantation be affected during the COVID-19 outbreak?

During the COVID-19 outbreak, planned autologous stem cell transplant (ASCT) for patients may be postponed to a more suitable time.

High-dose therapy (usually high-dose melphalan), and the ASCT procedure itself, weaken the immune system and potentially make myeloma and AL amyloidosis patients more susceptible and less able to fight infections like COVID-19. Patients who undergo ASCT also need to regularly attend hospital appointments for monitoring, increasing the risk of COVID-19 transmission through social interactions.

The decision about whether an ASCT will proceed during this time can only be made between a patient and their doctor. This decision is likely to be based on specific factors, including:

• The risk of myeloma progressing if they do not have an ASCT.
• The ability of a hospital to effectively isolate patients undergoing ASCT.
• The capacity of the intensive care unit within the hospital.
• The burden of COVID-19 in the region and country where the hospital is based.

As with all treatment decisions during the COVID-19 outbreak, the benefits and risks of a patient undergoing ASCT must be balanced. In most European countries, ASCT is taking place only where it is considered the best and most appropriate course of action for a patient.

If patients have any specific questions or concerns about their ASCT, they should talk directly to their doctor, nurse or healthcare team.

If autologous stem cell transplantation is delayed, what treatment will patients receive instead?

If a myeloma or AL amyloidosis patient has their autologous stem cell transplant (ASCT) postponed, the doctor will discuss an alternative treatment approach with them. In most cases, the doctor will extend the number of cycles of induction therapy that patients receive prior to ASCT.

Induction therapy consists of a combination of treatments, usually including a chemotherapy, a novel agent and a steroid. It is designed to induce a patient’s myeloma into a deep remission prior to undergoing ASCT.

In normal transplantation, patients undergo a defined number of cycles of induction therapy and then move onto ASCT. However, due to the situation with COVID-19, doctors may decide to extend the number of cycles. The aim here is to maintain the patient’s response to induction therapy, enabling them to defer ASCT to a later date. Alternatively, in some hospitals, doctors may keep the same number of induction cycles as usual but then drop down to a lower maintenance dose of the treatment – either with the same two-three drug combination or with lenalidomide maintenance.

With current myeloma treatment, patients can achieve very deep and durable responses to induction therapy, so it is possible to delay transplantation safely. Scientific evidence also shows that patient outcomes are not negatively affected if they have their transplant postponed.

What if a patient does not achieve a good response to their induction therapy?

As with all other myeloma treatment, doctors will continuously review a patient’s response to induction therapy and will amend the treatment approach if a patient is not responding well. This might include switching to an alternative treatment regimen or adding further cycles of treatment.

How will treatment with intravenous and subcutaneous drugs be affected during the COVID-19 outbreak?

During the current COVID-19 outbreak, doctors will be reviewing patients’ treatment on a case-by-case basis. This review should be done in consultation with the patient and will include an assessment of whether it is necessary for them to continue attending hospital to receive subcutaneous (i.e. an injection through the skin) or IV (i.e. infusion through the vein) treatment, where relevant.

If a patient is currently receiving IV or subcutaneous treatment and it is working well for them, or it is the only available option, they will continue to receive it and will be asked to attend hospital appointments as normal.

In some circumstances, amending the dose or administration of a treatment may be considered an appropriate course of action. This will be based on clinical evidence and should be fully explained to a patient.

Examples that MPE is aware of in European hospitals include:

• Reducing treatment with carfilzomib to once-weekly instead of twice-weekly, based on evidence from clinical trials.
• Implementing programmes of home administration of bortezomib (Velcade®), where safe, feasible and appropriate.
• Reducing the frequency of daratumumab infusions, given the long half-life of treatment.
• Replacing subcutaneous and IV proteasome inhibitors (such as bortezomib and carfilzomib) with the oral proteasome inhibitor ixazomib (Ninlaro®).

Depending on how a patient is responding, it might also be an appropriate point to stop treatment if a deep and durable response has been achieved.

Importantly, any changes made to treatment should be made in consultation with patients. If patients have any worries or concerns, they should speak directly to their doctor, nurse or healthcare team. It is important for patients to continue attending hospital appointments and to take their myeloma treatments as normal, unless instructed otherwise by their doctor, nurse or healthcare team.

What if a patient is about to start on a new treatment involving IV or subcutaneous administration?

If a patient is about to start a new IV or subcutaneous treatment, a myeloma and/or AL amyloidosis doctor is likely to assess whether this is the appropriate treatment for a patient during the COVID-19 outbreak.

Many patients will continue with their treatment as planned, if this is considered the best option.

However, some patients may be put onto an alternative oral treatment regimen, which they can take at home. There are a number of safe, effective and routinely used oral regimens in myeloma and AL amyloidosis such as pomalidomide (Imnovid®), lenalidomide (Revlimid®) and ixazomib (Ninlaro®).

What if oral treatment alternatives are not available in my country?

The availability of some medicines and how they are used will depend on funding from national healthcare systems.

In some countries, such as Spain, the oral proteasome inhibitor ixazomib, is not currently funded by the healthcare system for patients. These restrictions may make it more difficult for patients and their doctors to access certain oral treatment regimens during this time.

Many national healthcare systems, reimbursement bodies and doctors are working to address medicines access challenges in these exceptional times. Keep an eye out for published guidance and speak to your doctor if you have any specific questions or concerns.

MPE is also working with pharmaceutical companies, doctors and our members in individual countries to understand the situation across Europe and to identify and discuss solutions to address these challenges.

How will my treatment with steroids be affected during this time?

The steroids dexamethasone and prednisolone have immunosuppressive effects, reducing the ability of the immune system to fight infections. For myeloma and AL amyloidosis patients, who are already more susceptible to infection, this could further reduce their ability to fight COVID-19.

Many myeloma and AL amyloidosis patients will currently be taking dexamethasone or prednisolone as part of their treatment, either in combination with other drugs or as a high-dose therapy. Doctors will review the dose of steroids a patient is receiving as part of their treatment and decide whether it is appropriate to reduce the dose or even stop the steroids entirely.

Amending the dose of steroids is something that is done frequently in European clinical practice, given the effects that they can have on the quality of life of a patient (e.g. mood swings, insomnia). The experience that doctors have with this treatment will guide them in their decision-making with patients.

How will my bisphosphonate treatment be affected during the COVID-19 outbreak?

Many myeloma patients receive treatment with bisphosphonates (e.g. bone-strengthening drugs) for myeloma bone disease. The intravenous bisphosphonate, zoledronic acid, is a standard of care bisphosphonate treatment in many European countries – particularly for newly diagnosed patients. In some hospitals the IV bisphosphonate pamidronate might be used.

Patients who require bisphosphonate treatment may be offered the oral bisphosphonate sodium clodronate, as an alternative to IV bisphosphonates during this time. A doctor may also reduce the dose frequency of the IV bisphosphonate, for example, zoledronic acid can be given once every three months.

Where patients are currently receiving zoledronic acid and have been for a long time, bisphosphonate treatment may be stopped during the COVID-19 outbreak as their bone disease is under control.

HOSPITAL APPOINTMENTS

How will hospital outpatient appointments be affected during the COVID-19 outbreak?

Many myeloma and AL amyloidosis treatment centres in Europe are reviewing their patients on a case-by-case basis and assessing whether planned hospital outpatient visits (e.g. for disease monitoring, blood tests and treatment) are necessary.

In most hospitals, patients will be called by a doctor, nurse or member of the healthcare team to develop a plan for their treatment and care during the current period.

For patients with low-risk smouldering myeloma and monoclonal gammopathy of undetermined significance (MGUS), it is likely that any upcoming appointments will be rescheduled to a later date when social distancing measures have been relaxed. This may also apply where a patient has been in remission (e.g. stable disease) for a long period and is not experiencing any symptoms.

Some hospital appointments may be unavoidable for patients, but healthcare teams are working hard to reduce the need to come to hospital where possible. Many hospitals are moving towards telemedicine, where appointments and the discussion of blood test results take place via telephone or online video-call, where appropriate. Prescription medicines for myeloma and AL amyloidosis may also be delivered by mail to patients to save them attending hospital pharmacies to collect them. In some cases carers will be allowed to collect medicines from hospital pharmacies to avoid patients having to attend hospital.

Patients should speak to their healthcare teams to understand exactly how their hospital appointments will be affected.

CLINICAL TRIALS

How will clinical trials be affected during this time?

Clinical trials require patients to attend frequent hospital appointments for treatment, care and monitoring. Some clinical trials may also include quite intensive procedures such as CAR-T, requiring support from intensive care units given the neurotoxic side-effects (e.g. cytokine release syndrome). For these reasons, patient participation and recruitment to clinical trials may be affected in the coming months.

MPE is working to get a picture of how both industry-led and academic-led clinical trials are affected during the COVID-19 outbreak for myeloma and AL amyloidosis. Whilst it may vary from hospital to hospital, we are currently aware of the following impact:

• In many hospitals there is a blanket policy to stop recruiting new patients to myeloma and AL amyloidosis clinical trials. Ongoing participation in clinical trials, where patients are already enrolled, is being reviewed by doctors on a case-by-case basis and discussed with patients.
• Some clinical trials are being postponed and are no longer recruiting patients to participate during this time. These will reopen for participation later. Many trials in CAR-T and Phase I clinical trials (for example where the treatment is experimental, requiring extensive monitoring have been suspended in some hospitals.
• Other clinical trials may have revised protocols to adapt the number of patient hospital appointments. This is particularly possible where a trial involves a frequently used treatment in myeloma or AL amyloidosis, as doctors do not have to monitor safety in the same way as more experimental treatments.
• Conversations are being held by doctors and trial co-ordinators on how to better provide some of the monitoring and appointments associated with trials in a more remote setting (e.g. by telephone).

If a patient is already enrolled in a clinical trial and their treatment is affected, they will be informed by their doctor and an appropriate treatment discussed. Conversations will then be held around alternative treatment options which will enable them to reduce visits to hospital or receive their treatment at home.

Where a clinical trial is the only available option for a patient, doctors and researchers are working to ensure that patients continue to receive treatment and to participate in the clinical trial. MPE is also aware of compassionate use programmes of new medicines in myeloma being used in some countries to help patients access treatments outside of a clinical trial setting.

ACKNOWLEDGEMENT

Myeloma Patients Europe would like to acknowledge the doctors who provided input about the COVID-19 situation and it impacts on myeloma and AL amyloidosis treatment.

Thank you for their valuable input to:

• Prof Dr Heinz Ludwig, Professor of Internal Medicine and Haemato-Oncology and chair of the Wilhelminen Cancer Research Institute at the Department of Medicine I, Centre for Oncology and Haematology, Wilhelminenspital, Vienna, Austria.
• Dr Anna Sureda, Head of Haematology at the Catalan Institute of Oncology, Barcelona, Spain.
• Prof Dr Mohamad Mohty, Professor of Hematology and head of the Hematology and Cellular Therapy Department at the Saint-Antoine Hospital at University Pierre and Marie Curie, Paris, France.
• Dr Michel Delforge, Professor of Medicine in the Department of Hematology at the Catholic University of Leuven, Belgium.
• Dr Charlotte Pawlyn, Institute of Cancer Research, London, UK.
• Prof Dr Hermann Einsele, Professor of Internal Medicine, Director of the Department of Internal Medicine II of the University Hospital Würzburg, Germany.