August 13, 2020

This past week, the IMF hosted a Global Roundtable of myeloma experts to develop International Myeloma Working Group (IMWG) recommendations for the COVID-19 pandemic. Myeloma researchers from the Asia Pacific region, Europe, and the United States participated. (Input from Latin America is forthcoming.) 

While all IMWG participants in the upcoming 2020 IMWG Summit, August 25-27, will be involved in determining IMWG Guidelines for myeloma patient treatment during the current, as well as any future pandemic, this initial work group reviewed currently available information and discussed tentative guidelines. 

Our discussion focused on these four key areas: 

1. The remarkable differences in the pattern of covid-19 infections in myeloma patients around the globe. 

The origin of the COVID-19 pandemic and the timeline of its spread throughout the Asia Pacific region, then to Europe, the U.S. and other global regions were mapped out. Each group then summarized its experiences with myeloma patients during COVID-19. Findings on this topic have already been published by research teams based in the UK, Spain, and in the U.S. (Mount Sinai, Memorial Sloan Kettering). A table summarized the results.

There is a striking absence of cases of COVID-19 infections in myeloma patients in Asia. This is wonderful and truly remarkable. After repeated follow-up questions from the Roundtable participants, there is no doubt that throughout Asia there have been no COVID-19 infections in myeloma patients and no COVID-19-related deaths. Minor exceptions are China and Australia, where rare cases have been noted and probably one or two deaths have occurred.

What explains the absence of cases of COVID-19 infections in myeloma patients in Asia? The Roundtable discussion pointed to several factors:

• Traditional cautions in Asia regarding infectious diseases and the frequent use of masks in public.
• Very rapid implementation of excellent public health measures based upon prior experiences with SARS and other infections. In Taiwan, for example, excellent public health measures were immediately introduced.
• The frequent involvement of specialized referral centers in the care of myeloma patients. The IMF has a Clinical Trials network throughout Asia called the Asian Myeloma Network (AMN). Within that group, the experienced investigators implement Asia-specific Myeloma Guidelines published by the group. This undoubtedly helped.
• Early exposure to the initial COVID-19 “Wuhan strain” in Asia. Evidence now indicates that a new strain emerged in Europe, primarily in the Lombardy region of Italy, which is more infectious and has a different pattern of diseases. This more infectious strain subsequently became the dominant strain in New York, the rest of the U.S. (spreading from East to West, then South), as well as globally where travel was not blocked. By the time this strain emerged, travel to Asia was blocked. Thus, Asian patients largely avoided exposure to a more dangerous strain of COVID-19. Conversely, in the U.S. and Europe, more COVID-19 infections emerged, and, unfortunately, a significant number of deaths occurred.   
• With the implementation of rapid public health measures in Asia, the level of community spread remained low. There were no major surges beyond the original massive surge in Wuhan, which is where an occasional myeloma patient may have been infected, and hospital resources were not overwhelmed, as happened in Italy, Spain, the UK, and sequentially across the U.S. and around the world.

Sobering results of covid-19 infections in Europe and the U.S. (especially in the UK and New York) confirm the danger for myeloma patients, particularly if active disease and/or if any higher risk features are present. The 20-30% mortality for patients developing serious lung complications is an enormous warning to avoid exposure and COVID-19 infection if possible. 

Preventing exposure and infections in myeloma patients is the number one priority right now! 

2. Safety measures for myeloma patients. 

Roundtable participants strongly endorsed the need to adhere to safety measures, including wearing masks, physical distancing, avoiding crowds and cramped indoor spaces, and employing careful hygiene. As I’ve emphasized repeatedly in previous blogs, outdoor spaces are far safer than indoors.

The lack of rapid testing capability (for COVID-19 itself rather than antibodies) in the U.S. drew concern from Roundtable participants. This severely limits the ability to test, trace and quarantine effectively. This crucial deficiency is leading to ongoing community spread and many deaths. It was just announced that two companies will attempt to ramp up to provide rapid testing capability, but not at a scale nor in a timeframe that will help quell the current surges.
It also means that strategic or so-called smart lockdowns centered around new clusters are really impossible. Thus, the very unpopular prospect of broader lockdowns will be nearly unavoidable. 

It would be great if we could follow the lead of New Zealand. After an initial lockdown, infections were brought down to zero for 102 days. Four new cases emerged this week south of Auckland (original source unknown so far).  With a local strategic lockdown, rapid testing, tracing and quarantine, it should be possible to crush this minor new cluster almost immediately. This is the way things should work.

3. Treatment for myeloma during the pandemic.

The primary recommendation from the Roundtable participants is that every effort should be made to continue with the best therapies to treat myeloma and to sustain remissions. This must be the goal. If there is a community surge in COVID-19 infections, then a variety of emergency options can be used, including:
 

• Telemedicine appointments, to reduce the need for clinic and hospital visits. This may be an ongoing helpful option for a number of patients.
• Temporarily cut back on intravenous bisphosphonate infusions.
• Delay ASCT or CAR T-cell therapies if hospital resources are a concern.
• Use oral options, but not if treatment efficacy is being compromised.
• Reduce doses or modify regimens to avoid infections, if necessary. But the goal is to return to using recommended therapies as soon as feasible. 

4. New options for COVID-19 therapy and/or management.

The options under discussion by the Roundtable participants included:

• The use of blood thinners. We are just now starting to understand the problem with micro-clotting in COVID-19, and how best to use blood thinners.
• Mixed feedback about efficacy of convalescent plasma. 
• The status of vaccines for the immune-compromised and/or elderly population.  
• The lack of any dramatic or unexpected benefits with touted therapies such as dexamethasone, interferon or other antiviral cocktails.   

Much more work needs to be done related to trials for antiviral therapies and vaccines in order to bring all of the amazing efforts to fruition. The early release of the vaccine from Russia has raised a lot of concerns. How do we really know that vaccines coming to the market are truly safe and sufficiently effective, especially for vulnerable, elderly and immune-compromised groups?

We now know so much more than we did at the outset of the pandemic which measures keep myeloma patients safe from COVID-19 infection. And in the last three months, dozens of new studies have emerged that need to be evaluated. Our next step is to bring together an even larger pool of researchers from around the world to compare experiences and create guidelines for action in the face of a global health crisis. The IMWG will issue a final report after the full IMWG Summit convenes later this month. I will keep you posted!

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