role of experts

International Myeloma Working Group

New relapse guidelines highlight key role of IMWG experts

By Dr. Brian G.M. Durie IMF Chairman of the Board

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 Dr. S. Vincent Rajkumar (Mayo Clinic, Rochester), the 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 Revlimid® (lenalidomide) treatment, which is a widely used oral immunomodulatory agent for both primary therapy and maintenance. To fully assess these and other groups of patients, the IMWG team led by Dr. Philippe Moreau (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 approval from the U.S. Food and Drug Administration (FDA) in the relapsed setting, newer therapies 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 more than 50 publications on myeloma and its related disorders in prestigious journals, including major reference papers such as the following: • Diagnostic criteria for myeloma, • New criteria for response assessment and the role of minimal residual disease (MRD),

• Risk stratification for smoldering myeloma, • Myeloma-related bone disease therapy guidelines. From doctors to patients, the goal of the IMWG publications is to help better understand aspects of myeloma, and to help guide patients and their doctors to treating myeloma in the most effective way for every individual case.

Role of mass spectrometry

Another recently published manuscript is the IMWG committee report on mass spectrometry for testing in myeloma and the whole range of plasma cell disorders. This report was sufficient to support appropriate reimbursement for this important test methodology, which will soon replace standard serum protein electrophoresis (SPEP) and immunofixation (IFE) test 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 Darzalex® (daratumumab), the anti-CD38 monoclonal antibody 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 the 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! MT

The mission of the International Myeloma Working Group (IMWG) is to conduct collaborative basic, clinical, and translational research to improve outcomes for myeloma patients while providing scientifically validated, critically appraised consensus guidelines for the myeloma community globally. Creating, supporting, and hosting the important work of the IMWG and its members is a critical element of the IMF’s mission to expand myeloma research and to educate myeloma patients around the world. For more information, please visit imwg.myeloma.org.