Frequently asked questions | Treating patients with multiple myeloma during the COVID-19 pandemic

The Multiple Myeloma (MM) Hub are proud to have produced a variety of resources on the management of coronavirus disease (COVID-19) during the SARS-CoV-2 pandemic, specifically for hematology patients such as those with MM. This article is based on a webinar arranged by the International Academy for Clinical Hematology (IACH), whereby MM Hub Co-Chair, Maria-Victoria Mateos, and MM Hub Steering Committee Member, Mohamad Mohty, discussed practical advice for treating patients with MM during the COVID-19 pandemic.

Why are patients with MM more susceptible to infection?

There are three main reasons; the first is that MM is, by nature, an immunosuppressive disease. Secondly, patients with MM tend to be older, which is a risk factor for more severe infection. Lastly, many of the treatment regimens in MM lead to immunosuppression.

Should we postpone frontline autologous stem cell transplant (auto-SCT)?

It is important to assess patients individually, with an aim of managing their disease. The situation is dynamic and also varies between countries. The main advice for patients planned for auto-SCT is

• Delay auto-SCT where possible to avoid exposure to melphalan and myeloablative conditioning regimens which lead to weeks of cytopenias and therefore significantly increase the risk of COVID-19 infection
  • Increase the number of induction cycles until maximum response or plateau is reached and then move directly to maintenance
• If there is no alternative and there is no institutional block, it is recommended to test for COVID-19 prior to the start of conditioning

In clinical trials, the main difference in outcomes between patients receiving auto-SCT versus further cycles of induction is in progression-free survival, and not overall survival. Therefore, there is no anticipated impact of delaying auto-SCT on patient outcome.

Should we continue with stem cell mobilization and collection? What are the effects of increasing the number of induction cycles?

• Many apheresis units are closed in order to reduce the circulation of patients within units and reduce hospital visits
• If apheresis goes ahead:
  • Test patients for SARS-CoV-2
  • Use G-CSF instead of cyclophosphamide for stem cell mobilization
• If auto-SCT is delayed, future mobilization with the use of plerixafor or other mobilizers should still be possible

What is the advice for patients receiving maintenance with agents like lenalidomide and bortezomib?

• Consider the pandemic as a bridging period with an aim of maintaining disease control and the level of response that was previously achieved
• For a patient with a complete response or very good partial response post-auto-SCT:
  • Continue maintenance with lenalidomide monotherapy (no dexamethasone)
    • The effects of lenalidomide are immunomodulatory rather than anti-tumor. Therefore, lenalidomide can act well in this bridging scenario
    • Deliver the therapy at home to avoid hospital visits
  • For patients where lenalidomide is not well tolerated, especially hematologically, or in patients who have previously reported infections, consider stopping maintenance during this period
• Outside the transplant setting e.g. elderly patients on long-term continuous therapy:
  • For elderly patients on continuous lenalidomide plus dexamethasone therapy:
    • Stop dexamethasone
    • Reduce the dose of lenalidomide where possible
  • In patients who have finished (for example), nine cycles of lenalidomide with low-dose dexamethasone, discontinuation can lead to disease evolution so it is important to maintain lenalidomide treatment, except in patients at high-risk of infection  

Is there an optimal frontline therapy for patients with newly diagnosed MM at this time?  

• Standard of care (SOC) regimens like bortezomib, lenalidomide and dexamethasone (VRd); bortezomib, cyclophosphamide and dexamethasone (VCd); and bortezomib, thalidomide and dexamethasone (VTd) remain the recommended frontline therapies
  • It is important to evaluate each new patient on a case-by-case basis
• Since bortezomib is be involved in all these SOC triplets, optimizing the administration of bortezomib is important
  • Subcutaneous administration
  • Switch to weekly administration
  • Where possible, deliver bortezomib at home
  • Where not possible, ensure the patient is in hospital for as little time as possible; for example, calling staff when patients arrive at the hospital so they can be brought to the unit only when the drug is ready to be delivered
• Many pharmacies are also now permitted to prescribe immunomodulatory drugs (IMiDs®) like lenalidomide for two months at a time

Should the dose of dexamethasone be adapted?

The use of steroids may be associated with a high-risk of severe COVID-19 infection. Therefore, dexamethasone should only be continued in patients where absolutely necessary. Additionally, the lowest dose possible should be used – ideally 20 mg or 10 mg, with 40 mg per week being the maximum.

How should we handle the use of bisphosphonates?

Since bisphosphonates form part of supportive therapy, it is recommended their use is stopped temporarily during this time. This should not impact patient outcomes. The exception to this is in the case of hypercalcemia whereby a patient would likely be admitted to hospital and receive bisphosphonates in this setting.

Should dosing of anti-CD38 monoclonal antibodies (mAbs) be changed?

It is possible to change the duration of cycles to 5 weeks instead of the conventional 4-week cycles to reduce the number of visits and administrations.

Are any changes to combination therapies in the relapse setting recommended?

In some cases, triplet regimens being used in the relapse setting may be reduced to only two agents. Often a mAb or carfilzomib may be discontinued, with patients continuing only on lenalidomide plus dexamethasone or lenalidomide monotherapy. This is with an aim of reducing hospital visits.

Is there a role for agents such as ixazomib or cyclophosphamide?

Ixazomib is an orally available proteasome inhibitor that represents a good alternative option for many patients. It was noted that ixazomib is not approved in some countries; for example, in Spain there is compassionate use program only. It was also noted that cyclophosphamide (50 mg/m² every other day) has an immunomodulatory effect and can accompany lenalidomide or pomalidomide combinations.

How should we handle MM therapy in patients suffering from COVID-19?

• Hold all therapy in patients with MM who are infected with SARS-CoV-2
• Carefully monitor these patients
• Ensure multidisciplinary team management

What is happening to clinical trials during the pandemic?

Most clinical trials have stopped enrolment. This is predominantly because institutions and companies cannot ensure the safety of patients since clinical trials often require multiple visits to hospitals and the screening process requires visits to multiple departments. In future, these patients can be recruited onto clinical trials, but now is not the optimal time and involves unnecessary risk.

Key messages

• Consider each patient individually
• Maintain disease control
• Analyze the risk–benefit ratio of any treatment decisions

Additional resources

Expert opinions

• The impact of COVID-19 on the management of patients with multiple myeloma: The Italian experience. This article was written by Elena Zamagni, Paola Tecchetti and Michele Cavo, Bologna University School of Medicine, Bologna, IT
• Recommendations for the management of patients with multiple myeloma in the United States during the COVID-19 pandemic. This article was written by Deepu Madduri, Mount Sinai Hospital, New York, US
• Mohamad Mohty: COVID-19 and multiple myeloma. This article is a transcript from an interview held between the MM Hub and Mohamad Mohty

Recommendations and guidelines

• COVID-19 and EBMT recommendations for patients with hematological malignancies
• Caring for patients with hematological malignancies during the COVID-19 pandemic. Recommendations from IACH, EHA, and EBMT

Other hematological malignancies

The effect of COVID-19 on the management of patients with lymphoma. This article was written by Stefano Luminari and summarizes guidance for the treatment of patients with lymphoma