March 11, 2021
The International Myeloma Working Group (IMWG) has published new guidelines for the treatment of patients with relapsed or refractory (resistant to treatment) myeloma in the March 2021 issue of The Lancet Oncology.
Authored by the world’s top myeloma experts, this manuscript analyzes the results of phase II and III clinical trials and creates a rational approach to therapy. As noted by S. Vincent Rajkumar, MD, of the Mayo Clinic and co-chair of the IMWG: “Management of relapsed and refractory myeloma is extremely complex, with numerous drugs and regimens to choose from. This guideline provides specific recommendations that will greatly help hematologists and oncologists in managing patients with relapsed myeloma.”
A major classification feature is whether or not patients are resistant to prior lenalidomide (Revlimid) treatment, which is a widely used oral immunomodulatory therapy used for both primary therapy and maintenance. To fully assess these and other groups of patients the IMWG team, led by Dr. Philippe Moreau of University Hospital Hôtel-Dieu, Nantes, France, examined all clinical trials on relapsed myeloma published in English from 2013 to 2020. The summary and analyses of this large number of manuscripts is a huge resource for practicing hematologists and oncologists, as well as for patients and healthcare professionals overall.
Although the major focus is on therapies that have received FDA approval in the relapsed setting, newer therapies such as CAR T-cell immune approaches are also discussed.
The recommendations consider both the number of prior therapies, as well as how to deal with both access and costs around the world. If certain combinations are not available or not feasible, then alternative options are provided. The substantial disparities in drug availability around the world represent an enormous ongoing challenge and are increasingly a focus of attention for IMWG members.
Putting the IMWG in perspective
There are currently 256 IMWG members who are myeloma experts from around the globe. The ongoing collaborations have resulted in over 50 publications in prestigious journals, including major reference papers such as Diagnostic Criteria for myeloma, Criteria for response to treatment incorporating assessment of minimal residual and Risk Stratification for smoldering myeloma. Last week I mentioned the new bone therapy guidelines.
Role of mass spectrometry
Another recently published manuscript is the IMWG committee report on mass spectrometry for testing in myeloma and the whole range plasma cell disorders. This report was sufficient to support appropriate reimbursement for this important test methodology, which will soon replace standard SPEP and IFE methodologies for both diagnostic and monitoring purposes.
Mass spectrometry can distinguish between very low levels of myeloma protein and blood levels of monoclonal antibodies such as daratumumab (the anti-CD38 monoclonal antibody Darzalex) used in treatment and potentially confused with residual myeloma protein. Sorting out the distinction allows confirmation of complete remission (the apparent residual “spike” is actually Darzalex NOT myeloma protein). This confusion can occur in the low range of 0 to 0.4mg/dl of spike.
In addition, a sensitive version of mass spectrometry can also assess myeloma disease at a level similar to MRD testing. This means that a simple blood test can be used for very low-level disease-monitoring, which is much more attractive for patients than repeated bone marrow sampling!
COVID-19 Pandemic Updates
Vaccination is strongly encouraged for all myeloma patients. Whichever vaccine is available (Pfizer, Moderna, Johnson & Johnson), please proceed with vaccination as early as possible. All of these vaccines are 100% effective in eliminating the risk of severe disease, which is the main goal. The one-dose Johnson & Johnson vaccine is obviously quite convenient.
Talk to your doctor if you have concerns about your particular treatment situation. If you are just recovering from an autologous stem-cell transplant (ASCT), then vaccination should be delayed by a month or two. Otherwise, it is safe to proceed. I suggest a commonsense adjustment to your treatment around the timing of vaccination. For example, try to get vaccinated during the week off from maintenance (such as with Revlimid). Do not take more intensive treatment, such as Darzalex on the same day as vaccination. However, be very cautious about any extended delays in treatment, since the top priority is still to keep your myeloma in remission. Adjustments for a few days around the day of vaccination are sufficient.
Myeloma patients should continue to wear masks. You just do NOT want to take any risk of getting infected. If you get infected with one of the new COVID-19 variants, then chances are any infection will be very mild if you have been vaccinated. However, it is still better not to get infected. The new CDC guidelines for those who are vaccinated say it is okay to get together in small groups with grandchildren. This is an encouraging step forward. However, flying to visit them is still not a great idea, at least until more people are vaccinated and community levels of infection are lower. Italy may have the right idea—this week the country unveiled “covid-free” trains to tourist destinations.
After a year, everyone is feeling the impact. Our lives are just not the same and the tragic losses in our communities are truly unbearable. The new COVID Relief Bill is definitely a triumph and will definitely help in the day-to-day and ongoing recovery for everyone.
The IMF Boca Patient & Family Seminar on Saturday, March 13 will include tips for reducing stress in these challenging times. And in the meantime, let me again recommend watching the “Penguin Walks” from the Shedd Aquarium in Chicago. Watching the penguins visit the modern art museum (and the gift shop) will lighten your day—something we all need.
Dr. Brian G.M. Durie serves as Chairman of the International Myeloma Foundation and serves on its Scientific Advisory Board. Additionally, he is Chairman of the IMF's International Myeloma Working Group, a consortium of nearly 200 myeloma experts from around the world. Dr. Durie also leads the IMF’s Black Swan Research Initiative®.