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August 27, 2020

The IMF hosted the 11th Annual International Myeloma Working Group (IMWG) Summit in virtual fashion on August 25-26. Although it was held online, the Summit continued the tradition of focusing on the latest myeloma research from experts around the world.

An innovative platform allowed 60 IMWG members to participate, using a wall of interactive monitors to communicate with speakers and panelists. It was possible to have two-, three- and four-way conversations and invite commentary from those on the wall.

“It felt like we were all sitting in the same room,” noted Dr. Shaji Kumar (Mayo Clinic, Rochester, MN).

Additional comments arrived via chat box from more than 100 additional participants and observers.

Although everyone missed the camaraderie, the ability to chat personally, and the sharing of stories, the traditional structure of the Summit was retained: a Keynote Speech, this year by Prof. Kári Stefánsson, founder and CEO of deCODE genetics in Reykjavik, Iceland; four plenary lecture topics; and four Working Group Committee reports to the IMWG membership.

There were many takeaways from the two-day event. Here are the major highlights:

Keynote Address

Prof. Stefánsson presented a brilliant lecture on population genetics based on his more than 20 years of work at deCODE. He helped the audience understand the origin and impact of individual gene mutations on disease predisposition. He emphasized how clonal expansion of cells with particular mutations is required to have an effect in the body.

There has been only a little research so far on IgM-type MGUS. We now await with great anticipation the ongoing work of Prof. Sigurdur Kristinsson of the IMF’s Black Swan Initiative-supported iStopMM project to help reveal the genetic basis for MGUS overall and plasma cell disorders.

Plenary Lectures

Frontline therapy

The key question in this session, chaired by Prof. Pieter Sonneveld (Erasmus MC Cancer Center, The Netherlands) was whether or not we are heading toward the use of a four-drug combination—a quadruplet—in the frontline setting. The answer delivered by this panel was a decisive yes.

But many issues remain, not least of which are access and costs. After presentations by Dr. Vincent Rajkumar (Mayo Clinic, Rochester, MN) on triplets, and Dr. Paul Richardson (Dana-Farber Cancer Institute, Boston) on quadruplets, it was clear that further studies are needed to show decisively that a combination of, for example, Daratumumab (Dara) + Velcade (V) + Revlimid (R) + dexamethasone (d) produces better survival versus the triplet of VRd alone. This discussion linked directly to the next topic, Minimal Residual Disease (MRD) assessment.

Minimal Residual Disease (MRD) assessment

This session, chaired by Prof. Jesús San Miguel (University of Navarra, Spain), was comprehensive in covering:

  • The role of MRD testing as an endpoint (Dr. Nikhil Munshi, Dana-Farber Cancer Institute, Boston, MA).
  • The MRD tests currently available (Dr. Bruno Paiva, University of Navarra, Spain).
  • Whether or not MRD can be a surrogate indicator of potential cure (Dr. María-Victoria Mateos, University of Navarra, Spain).

MRD is an essential endpoint that indicates early on, the potential for very long survival. We all eagerly await the approval of MRD as a surrogate endpoint by the FDA! The data are being submitted by the i2TEAMM, a group of international myeloma researchers working to validate MRD testing as a surrogate endpoint superior to traditional endpoints, such as CR (complete remission) or even sCR (stringent complete response) in myeloma clinical trials.There is true optimism about approval in the coming months.

Immune therapies

This session, chaired by Dr. Thomas Martin (University of California, San Francisco) and Dr. Yi Lin (Mayo Clinic, Rochester, MN), examined the topic that garnered the most interest at the Summit: What will be the role of CAR T-cells? And what about bispecific antibodies? Dr. Saad Usmani (Atrium Health, Charlotte, NC) described these as “the poor man’s CAR T.”

The fact that belantamab mafodotin (Belamaf) was just approved by the FDA (and on the second day of the Summit, by the European Medicines Agency) was a focus of attention. There is great enthusiasm for using this new, anti-BCMA agent as a potent immune therapy in the relapsed setting. It is readily available (“off the shelf”) and has an easy, once-every-three-weeks administration schedule.

Overall, the sentiment was that each of the new immune therapies will have a niche and will move earlier and earlier in the treatment paradigm to take advantage of the unprecedented, very deep responses that are being achieved with CAR T-cell therapies, bispecifics, as well as the antibody drug conjugate Belamaf.

CAR T-cell therapies, it was noted, can be an attractive option for patients with high-risk disease in whom achieving deep MRD-negative response can be of particular benefit. There is also the notion that CAR T-cell therapies in particular may end up replacing traditional ASCT (autologous stem-cell transplant). Patient preference will continue to be an important part of all these types of management discussions.

On the research side, the establishment of a registry for patients treated with anti-BCMA therapies, as well as a virtual tissue bank, were enthusiastically discussed.

Relapse treatments

The highlight in this session, chaired by Dr. Joseph Mikhael (Translational Genomics Research Institute, Phoenix, AZ), was the review of the “New IMWG Guidelines for RRMM,” presented by Dr. Philippe Moreau (University Hospital Nantes, France). This has been a challenging project, but the final manuscript is ready for submission and publication. Important discussions emerged about what is recommended and what is truly feasible in many parts of the world. Many combinations, such as daratumumab + pomalidomide + dexamethasone, are not reimbursed nor actually available. As a result, less effective regimens must be substituted. This is really disheartening for doctors and unfair for patients. Broad solutions remain elusive.

Working Group Committees

Highlights from the IMWG Summit Working Group reports included:

  • A summary of the upcoming publication of guidelines for use of mass spectrometry, presented by Dr. David Murray (Mayo Clinic, Rochester, MN). This very sensitive blood-test technology will revolutionize both diagnostic testing and response monitoring in the coming years.
  • The new criteria for identification of high-risk smoldering myeloma (the 2/20/20 system), presented by Drs. Kumar and Mateos. These criteria are also just about to be published.
  • Planned projects and studies by the Immune Therapy Committee (led by Drs. Martin and Lin), which received enthusiastic endorsement.
  • The many accomplishments and upcoming plans by the Bone Committee (led by Dr. Evangelos Terpos, University of Athens, Greece, and Dr. Jens Hillengass, Roswell Park, New York).

2020 IMWG Awards

It was a real disappointment that in-person award presentations were not possible this year! However, Prof. Thierry Facon (University of Lille, France) was announced as the recipient of the 2020 Robert A. Kyle Lifetime Achievement Award and Prof. Wee Joo Chng (Singapore University) received the 2020 Brian G.M. Durie Outstanding Achievement Award. In lieu of the formal ceremony, both recipients provided heartfelt thanks and appreciation.

2020 IMWG Summit Closing Session

As usual, the closing session included a discussion of Treatment Algorithms from the U.S. Frontline options were presented by Dr. Vincent Rajkumar, while Dr. Moreau presented options in the relapsed setting. These practical recommendations for doctors are greatly appreciated, coming as they do from such noted experts.

We followed up with an open-question session, an extremely lively and productive discussion among panelists, IMWG members “on the wall,” and those who chimed in via the chat box. This format allowed many to raise questions of interest and concern, including suggestions for next year’s Summit. Dr. Bob Kyle was able to join in briefly, describing the incredible progress made in myeloma treatments over the past 20 years. It was an enormous treat for everyone!

In closing, IMF President, Founder, and CEO Susie Durie, and 2020 IMWG Summit co-chairs Drs. Rajkumar, San Miguel, Moreau and I expressed our appreciation for the active engagement and contributions of all participants. Congratulations and thank you to the IMF team behind the scenes: Lisa Paik (Senior Vice President, Clinical Education & Research Initiatives), Annabel Reardon (Director, Meetings & Events), Amirah Limayo (Senior Research Project Coordinator), Abigail Guzman (Meeting Registration & Guest Relations), Meghan O’Connor (Administrative Assistant, Meetings) and Miko Santos (Web Producer).

This unique virtual setting made for a truly memorable two days. Researchers around the world were able to continue the collaborations and interactions that are a feature of all IMWG meetings and that yield wonderful results for patients.

Translations

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Have questions? Dr. Durie sincerely appreciates questions submitted to [email protected]. However, he cannot answer specific medical questions and encourages readers to contact the trained IMF InfoLine staff instead. To contact the IMF InfoLine, call 800-452-CURE, toll-free in the U.S. and Canada, or send an email to [email protected]. InfoLine hours are 9 am to 4 pm PT. Thank you.


Image of Dr. Brian G.M. DurieDr. 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®.

 

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